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Duchenne muscular dystrophy (DMD, MIM #310200) and Becker muscular dystrophy (BMD, MIM #300376) are X-linked recessive hereditary diseases caused by pathogenic variants in the DMD gene. Genetic testing of DMD identifies a certain number of variants of uncertain clinical significance (VUS) whose functional interpretations pose a challenge for gene-based diagnosis. To improve the accuracy of variant interpretation in public mutation repositories, we used computational tools to prioritize VUS and developed a cell-based minigene assay to confirm aberrant splicing. Using this procedure, we evaluated rare variants in exon and intron 10 of the DMD gene. We demonstrated that 16 variants, including both canonical and non-canonical splice sites, altered RNA splicing in variable patterns. Using the example of exon and intron 10 of the DMD gene, we demonstrated the utility of the in vitro minigene assay in the effective assessment of the spliceogenic effect for VUS identified in clinical practice and underlined the necessity of precise variant classification. This is the first systematic characterization of DMD splicing variants, besides, through our study, some undetermined variants are demonstrated to be pathogenic by altering RNA splicing of DMD.

Background: Mounting evidence has shown that mechanical thrombectomy (MT) improves clinical outcomes for large vessel occlusions (LVOs) in patients with acute ischemic stroke (AIS) of the anterior circulation. The present study aimed to provide a comprehensive analysis of risk factors associated with clinical outcomes in AIS patients receiving MT. Methods: A total of 212 consecutive patients who underwent MT for AIS were enrolled in the present study. Clinical characteristics were recorded at admission. Two endpoints were defined according to the 3-month modified Rankin scale (mRS) score after AIS (good outcome, mRS 0-2; and death, mRS 6). Additionally, we compared the clinical outcomes and safety of MT alone and bridging therapy in AIS patients. Results: Of the 212 patients treated with MT, 114 (53.77%) patients had a good outcome and 31 (14.62%) died. The incidence of a worse outcome after MT was significantly elevated in males and patients with high WBC counts, high admission blood glucose levels, high baseline NIHSS scores and a long interval time from groin puncture to reperfusion in AIS patients treated with MT after adjustment for covariates (P Conclusion: Our constructed nomogram based on male sex, admission WBC, admission blood glucose, NIHSS, and the interval time from groin puncture to reperfusion predicts prognosis after mechanical thrombectomy in patients with acute ischemic stroke.

Oxidative stress and inflammation damage play pivotal roles in vascular dementia (VaD). Trimethylamine N-oxide (TMAO), an intestinal microbiota-stemming metabolite, was reported to promote inflammation and oxidative stress, involved in the etiology of several diseases. Still, these effects have not been investigated in VaD. Here, we tested whether pre-existing, circulating, high levels of TMAO could affect VaD-induced cognitive decline. TMAO (120 mg/kg) was given to rats for a total of 8 weeks, and these rats underwent a sham operation or bilateral common carotid artery (2VO) surgery after 4 weeks of treatment. Four weeks after surgery, the 2VO rats exhibited hippocampal-dependent cognitive function declines and synaptic plasticity dysfunction, accompanied by an increase in oxidative stress, neuroinflammation, and apoptosis. TMAO administration, which increased plasma and hippocampal TMAO at 4 weeks postoperatively, further aggravated these effects, resulting in exaggerated cognitive and synaptic plasticity impairment, though not within the Sham group. Moreover, TMAO treatment activated the NLRP3 inflammasome and decreased SIRT1 protein expression within the hippocampus. However, these effects of TMAO were significantly attenuated by the overexpression of SIRT1. Our findings suggest that TMAO increases oxidative stress-induced neuroinflammation and apoptosis by inhibiting the SIRT1 pathway, thereby exacerbating cognitive dysfunction and neuropathological changes in VaD rats.

Background Microglia assume opposite phenotypes in response to ischemic brain injury, exerting neurotoxic and neuroprotective effects under different ischemic stages. Modulating M1/M2 polarization is a potential therapy for treating ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) held the capacity to regulate neuroinflammation and astrocytic polarization, but little is known about rTMS effects on microglia. Therefore, the present study aimed to examine the rTMS influence on microglia polarization and the underlying possible molecular mechanisms in ischemic stroke models. Methods Previously reported 10 Hz rTMS protocol that regulated astrocytic polarization was used to stimulate transient middle cerebral artery occlusion (MCAO) rats and oxygen and glucose deprivation/reoxygenation (OGD/R) injured BV2 cells. Specific expression levels of M1 marker iNOS and M2 marker CD206 were measured by western blotting and immunofluorescence. MicroRNA expression changes detected by high-throughput second-generation sequencing were validated by RT-PCR and fluorescence in situ hybridization (FISH) analysis. Dual-luciferase report assay and miRNA knock-down were applied to verify the possible mechanisms regulated by rTMS. Microglia culture medium (MCM) from different groups were collected to measure the TNF-α and IL-10 concentrations, and detect the influence on neuronal survival. Finally, TTC staining and modified Neurological Severity Score (mNSS) were used to determine the effects of MCM on ischemic stroke volume and neurological functions. Results The 10 Hz rTMS inhibited ischemia/reperfusion induced M1 microglia and significantly increased let-7b-5p level in microglia. HMGA2 was predicted and proved to be the target protein of let-7b-5p. HMGA2 and its downstream NF-κB signaling pathway were inhibited by rTMS. Microglia culture medium (MCM) collected from rTMS treated microglia contained lower TNF-α concentration but higher IL-10 concentration than no rTMS treated MCM, reducing ischemic volumes and neurological deficits of MCAO mice. However, knockdown of let-7b-5p by antagomir reversed rTMS effects on microglia phenotype and associated HMGA/NF-κB activation and neurological recovery. Conclusion High-frequency rTMS could alleviate ischemic stroke injury through inhibiting M1 microglia polarization via regulating let-7b-5p/HMGA2/NF-κB signaling pathway in MCAO models.

Aging-related neurocognitive disorder (NCD) is a growing health concern. Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite from dietary precursors, might emerge as a promising biomarker of cognitive dysfunction within the context of brain aging and NCD. TMAO may increase among older adults, Alzheimer’s disease patients, and individuals with cognitive sequelae of stroke. Higher circulating TMAO would make them more vulnerable to age- and NCD-related cognitive decline, via mechanisms such as promoting neuroinflammation and oxidative stress, and reducing synaptic plasticity and function. However, these observations are contrary to the cognitive benefit reported for TMAO through its positive effects on blood–brain barrier integrity, as well as from the supplementation of TMAO precursors. Hence, current disputable evidence does not allow definite conclusions as to whether TMAO could serve as a critical target for cognitive health. This article provides a comprehensive overview of TMAO documented thus far on cognitive change due to aging and NCD.

BackgroundAlterations in the gut microbiota after ischemic stroke have been demonstrated, whereas the effect on stroke outcome remains to be established.MethodsA total of 132 consecutive patients with acute ischemic stroke were prospectively enrolled. Their gut microbiomes within 24 h of admission were profiled using 16S ribosomal RNA (rRNA) gene (V3–V4 region) sequencing. Microbiota comparisons were made between groups with good outcome (n = 105) and poor outcome (n = 27) based on 3-month modified Rankin Scale scores of 0–2 and 3–6. Propensity score-matching (PSM) analysis was conducted to assess the robustness of our findings. The functional potential was predicted using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt).ResultsPatients in the poor outcome group were characterized by a significant reduction in the alpha diversity (Shannon index, p = 0.025; Simpson index, p = 0.010), an increase in the pathogenic bacteria (e.g., Enterococcaceae and Enterococcus), and a decrease in the short-chain fatty acids (SCFAs)-producing bacteria (e.g., Bacteroidaceae, Ruminococcaceae, and Faecalibacterium) to those with good outcome group (all p < 0.05). Similar results of microbial composition were obtained after PSM. The PICRUSt revealed that the pathway for membrane transport was relatively dominant in patients with poor outcome (p < 0.05).ConclusionThis study demonstrated that stroke patients with 3-month poor outcome had baseline gut microbiota dysbiosis featured by increased pathogenic bacteria and decreased SCFAs-producing bacteria.

Stroke induces disorder of gut microbiota, however, whether this disorder differs according to stroke severity and its role in the evolution and outcome of stroke is currently unknown. Here we explored the composition and structure of fecal microbiome based on 68 acute ischemic stroke patients presenting with minor symptoms (admission National Institute of Health Stroke Scale (NIHSS) ≤ 3) and 67 patients with non-minor stroke (admission NIHSS 4-34) using high-throughput Illumina sequencing of the 16S rRNA. There was no significant difference in α-diversity indices, but the principal coordinate analysis of the microbiota indicated clear separation of the two groups. The significantly enriched butyrate-producing genus Roseburia in the minor stroke group was negatively correlated with fasting glucose, while the Erysipelotrichaceae incertae sedis abundant in non-minor stroke patients was positively correlated with stress hyperglycemia (i.e. fasting glucose/glycated hemoglobin ratio). Moreover, the relative abundance of genus Roseburia was also significantly associated with the dynamic changes of NIHSS score, as well as short-term and long-term functional outcomes. Our results suggested that stroke affects microbiota composition in a manner differentiated by stroke severity, and the enrichment of genus Roseburia may play a protective role in stroke evolution and outcome. Our findings strengthen the relevance of specific taxa for stroke severity that might allow targeted therapy in acute ischemic stroke.

Background: Recently, a new resting-state functional magnetic resonance imaging (rs-fMRI) measure to evaluate the concordance between different rs-fMRI metrics has been proposed and has not been in...

Recently, the NIHSS STroke Scale score, Age, pre-stroke mRS score, onset-to-treatment Time (START nomogram) predicts 3-month functional outcome after intravenous thrombolysis in ischemic stroke patients. However, this model has not yet been an external validation. We aim to validate the performance of START nomogram.Data were derived from the stroke center of the Nanjing First Hospital (China). Patients who lacked the necessary data to calculate the nomogram and missed 3-month modified Ranking scale scores were excluded. Modified Rankin Scale score more than 2 at 3-month was assessed as an unfavorable outcome. We used areas under the receiver operator characteristic curves (AUC-ROC) to quantify the prognostic value. Calibration was assessed by calibration plots and Hosmer-Lemeshow (HL) goodness of fit test.The final cohort included 306 eligible patients. For 3-month unfavorable outcome, the AUC-ROC of the START nomogram was .766 (95%CI: .7013-.8304, P.0001), suggesting good discrimination in the START nomogram. It also showed good calibration (HL goodness of fit test P = .1261) in the external validation sample.The START nomogram with good predictive performance is a reliable and simple clinical instrument to predict unfavorable outcome after acute stroke.

The ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) is an objective approach to predicting poor outcomes in acute ischemic stroke (AIS). The impact of TG/HDL-C on hemorrhagic transformation (HT) after AIS remains unknown. The aim of this study was to explore the accurate effect of TG/HDL-C on HT after AIS. We enrolled a total of 1423 patients with AIS in the training cohort from a prospective, consecutive hospital-based stroke registry. Of the 1423 patients, HT occurred in 155 (10.89%) patients. The incidence of HT after AIS was significantly increased when there were low levels of TG (P=0.016) and TG/HDL-C (P=0.006) in patients with AIS attributable to large artery atherosclerosis (LAA), but not in those who suffered from cardioembolic stroke. After adjustment for covariates, a lower TG/HDL-C (OR=0.53, 95%CI=0.20-0.93) that was more than TG alone (OR=0.61, 95%CI=0.27-0.98) independently increased the risk of HT in LAA. Furthermore, our established nomogram indicated that lower TG/HDL-C was an indicator of HT. These findings were further validated in the test cohort of 558 patients with AIS attributable to LAA. In summary, a low level of TG/HDL-C is correlated with greater risk of HT after AIS attributable to LAA.

Background: Accurate prognostication of unfavorable outcome made at the early onset of stroke is important to both the clinician and the patient management. This study was aimed to develop a nomogram based on the integration of parameters to predict the probability of 3-month unfavorable functional outcome in Chinese acute ischemic stroke patients. Methods: We retrospectively collected patients who underwent acute ischemic stroke at Stroke Center of the Nanjing First Hospital (China) between May 2013 and May 2018. After exclusion, the study population includes 1,025 patients for nomogram development. The main outcome measure was 3-month unfavorable outcome (modified Rankin Scale > 2). Multivariable logistic regression analysis was used to develop the predicting model, and stepwise logistic regression with the Akaike information criterion was utilized to find best-fit nomogram model. We incorporated the creatinine, fast blood glucose, age, previous cerebral hemorrhage, previous valvular heart disease, and NHISS score (COACHS), and these factors were presented with a nomogram. We assessed the discriminative performance by using the area under curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. Results: Multivariate analysis of the 1,025 patients for logistic regression helped identify the independent factors as National Institutes of Health Stroke Scale score on admission, age, previous valvular heart disease, fasting blood glucose, creatinine, and previous cerebral hemorrhage, which were included in the COACHS nomogram. The AUC-ROC of nomogram was 0.799. Calibration was good (p = 0.1376 for the Hosmer-Lemeshow test). Conclusions: The COACHS nomogram may be used to predict unfavorable outcome at 3 months after acute ischemic stroke in Chinese population. It may be also a reliable tool that is effective in its clinical utilization to risk-stratify acute stroke patients.

Background We aimed to assess the safety and efficacy of endovascular treatment (EVT) in patients with anterior circulation emergent large vessel occlusion (ELVO) beyond 6 h from symptom onset in a real-world cohort of patients in China. Methods We retrospectively examined 305 patients with anterior circulation ELVO treated with EVT. Patients were divided into two groups: treated with known onset within 6 h (n = 238) and beyond 6 h (n = 67). Multivariable logistic regression and ordinal shift analyses were used to evaluate the associations between onset-to-groin puncture time and safety and efficacy outcomes. Results Treatment beyond 6 h was not associated with symptomatic intracranial hemorrhage within 48 h (sICH; odds ratio [OR] 2.03, 95% confidence interval [CI] 0.48–8.57, p = 0.334), in-hospital mortality (OR 1.95, 95% CI 0.48–7.91, p = 0.348), successful recanalization (modified Thrombolysis in Cerebral Infarction score 2b or 3; OR 0.73, 95% CI 0.31–1.73, p = 0.470), favorable functional outcome (modified Rankin Scale score 0–2; OR 0.55, 95% CI 0.25–1.23, p = 0.145), and functional improvement (modified Rankin Scale shift by 1-point decrease; common OR 0.80, 95%CI 0.45–1.42, p = 0.450) at 3 months compared with treatment within 6 h. Futher interaction analysis showed that stroke etiology did not modify the associations between onset-to-groin puncture time and outcomes (p > 0.05). Conclusions In this real-world study, after careful assessment, EVT beyond 6 h from known stroke onset was safe, effective and had comparable short-term outcomes to EVT within 6 h.

Stroke-associated infection (SAI) is a major medical complication in acute ischemic stroke patients (AIS) treated with endovascular therapy (EVT). Three hundred thirty-three consecutive patients with AIS caused by a large vessel occlusion in the anterior circulation who received EVT (142 (42.6%) of them were given IV tPA as bridging therapy) and 337 AIS patients who received IV tPA only (non-EVT) were enrolled in the study and evaluated to determine the association of inflammatory factors on admission with SAI. Among the 333 AIS patients undergoing EVT, SAI occurred in 219 (65.8%) patients. Patients with SAI had higher baseline National Institutes of Health Stroke Scale (NIHSS) total scores, white blood cell (WBC) and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without SAI (P

Background: Mounting evidence has shown that mechanical thrombectomy (MT) improves clinical outcomes for large vessel occlusions (LVOs) in patients with acute ischaemic stroke (AIS) of the anterior circulation. The present study aimed to provide a comprehensive analysis of risk factors associated with clinical outcomes in AIS patients receiving MT.Methods: A total of 212 consecutive patients who underwent MT for AIS were enrolled in the present study. Clinical characteristics were recorded at admission. Two endpoints were defined according to the 3-month modified Rankin scale (mRS) score after AIS (good outcome, mRS 0–2; and death, mRS 6). Additionally, we compared the clinical outcomes and safety of MT alone and bridging therapy in AIS patients.Results: Of the 212 patients treated with MT, 114 (53.77%) patients had a good outcome and 31 (14.62%) died. The incidence of a worse outcome after MT was significantly elevated in males and patients with high WBC counts, high admission blood glucose levels, high baseline NIHSS scores and a long interval time from groin puncture to reperfusion in AIS patients treated with MT after adjustment for covariates (P Conclusions: The factors associated with an unfavourable outcome in AIS patients treated with MT were male sex, admission WBC, admission blood glucose, NIHSS, and the interval time from groin puncture to reperfusion.

A loading dose of antiplatelets reduces in-stent thrombosis after stent implantation. However, whether it is safe in patients undergoing acute stenting after intravenous recombinant tissue plasminogen activator (rt-PA) is unclear.A case series of acute ischemic stroke patients treated with intravenous rt-PA followed by emergent stenting were prospectively included in Jinling Hospital Stroke Unit. An emergent loading dose of antiplatelets (aspirin 300 mg and clopidogrel 300 mg) were administered to all patients through a nasogastric tube immediately before stenting. Clinical and angiographic outcomes were evaluated in these patients.A total of 12 patients were included. The median of NIHSS score on admission was 15 points (interquartile range 11-19). The median of time from stroke symptom onset to start IV rt-PA and stent placement was 172 min (interquartile range 123.75-189) and 311.5 min (interquartile range 285.5-349.5), respectively. All patients reached complete or partial recanalization (TICI ≥2a). One patient occurred hemorrhagic transformation at 24 h following the emergent loading dose of antiplatelets. A favorable outcome as defined by mRS ≤2 at 90 days was obtained in 58.3% (7/12) of all patients.Our finding preliminary suggested that an emergent loading dose of antiplatelets may be safe and feasible for acute stenting after IV rt-PA.

Background and Purpose: The clinical use of tirofiban for patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) remains controversial. We aimed to evaluate the safety and efficacy of tirofiban combined with MT in AIS patients. Methods: Patients with AIS who underwent MT from January 2014 to December 2018 were enrolled in three stroke units in China. Subgroup analyses were performed based on stroke etiology which was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Safety outcomes were in-hospital intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) and mortality at 3-month. Efficacy outcomes were favorable functional outcome and functional independence at 3-month and neurological improvement at 24 h, 3 d and discharge. Results: In patients with large artery atherosclerosis (LAA) stroke, multivariate analyses revealed that tirofiban significantly decreased the odds of in-hospital ICH (adjusted OR = 0.382, 95% CI 0.180–0.809) and tended to increase the odds of favorable functional outcome at 3-month (adjusted OR = 3.050, 95% CI 0.969–9.598). By contrast, in patients with cardioembolism (CE) stroke, tirofiban was not associated with higher odds of favorable functional outcome at 3-month (adjusted OR = 0.719, 95% CI 0.107–4.807), but significantly decreased the odds of neurological improvement at 24 h and 3d (adjusted OR = 0.185, 95% CI 0.047–0.726; adjusted OR = 0.268, 95% CI 0.087–0.825). Conclusions: Tirofiban combined with MT appears to be safe and effective in LAA patients, but has no beneficial effect on CE patients.

Objectives The accuracy of cognitive screening tools to detect poststroke cognitive impairment (PSCI) was investigated using various neuropsychological definitions. Methods Hospital‐based stroke patients underwent a comprehensive neuropsychological assessment. The rate of PSCI was estimated using thresholds of 1, 1.5, or 2 standard deviations below the normal control and memory impairment defined by a single or multiple tests. Meanwhile, the diagnostic accuracy of cognitive screening through face‐to‐face assessment using the Mini‐Mental State Examination (MMSE) and the Montreal Cognitive Assessment Scale (MoCA), and telephone assessment using a 5‐minute NINDS‐Canadian Stroke Network (NINDS‐CSN) scale and a six‐item screener (SIS), was both tested under different definitions, with the optimal cutoff selected based on the highest Youden index. Results In stroke patients, the rate of PSCI ranged from 46.3% to 76.3% upon different definitions. The face‐to‐face MoCA was more consistent with the comprehensive cognitive assessment compared to MMSE. The optimal cutoff of PSCI was MMSE ≤ 27 and MoCA ≤ 19. For the telephone tests, the 5‐minute NINDS‐CSN assessment was more reliable, and the optimal cutoff was ≤23, while for SIS ≤ 4. Conclusions Cognitive screening tools including the face‐to‐face MMSE and MoCA, together with the telephone assessment of NINDS‐CSN 5‐minute protocol and SIS, were simple and effective for detecting PSCI in stroke patients. The corresponding threshold values for PSCI were 27 points, 19 points, 23 points, and 4 points., The rate of cognitive impairment varied as neuropsychological definitions differed. Cognitive screening cutoffs for MMSE, MoCA, NINDS‐CSN 5‐minute protocol, and SIS were 27, 19, 23, and 4.

Clinical tools predicting brain edema after reperfusion therapy in acute ischemic stroke are scarce. We aim to develop a nomogram model to predict brain edema within the first 24 h after endovascular treatment (EVT) in the anterior cerebral circulation.A total of 199 patients were retrospectively identified in a single-center stroke registry. Brain edema was measured by midline shift (MLS). The associations between MLS and early neurologic outcomes were described. A nomogram predicting MLS was developed and internally validated. The nomogram was also compared with an available model using the area under the receiver operating characteristic curve (AUC) and decision curve analyses.Overall, 87 patients (43.7%) had MLS. The patients with MLS ≥ 6 mm showed progressive neurological deterioration according to repeated measures analysis of variance. Each millimeter increase in MLS was strongly correlated with the presence of in-hospital death or forgoing treatment (Spearman's rho = 0.429, P .001). Patients with brain edema were less likely to have functional independence at 3 months (19.5% vs. 46.8%, P .001). A nomogram model including 24-h CT ASPECT scores and cisternal effacement, hypertension and complete recanalization showed a C-index of 0.874. This tool exhibited a higher AUC and higher net benefit than the available model.This study showed a profound association between MLS and early neurologic outcomes. A nomogram model was developed to predict patients at risk of brain edema after EVT in the anterior cerebral circulation.

Background Early prediction of unfavorable outcome after ischemic stroke is of great significance to the clinical and therapeutic management. A nomogram is a better visual tool than earlier models and prognostic scores to predict clinical outcomes, which incorporates different factors to develop a graphic continuous scoring system and calculates accurately the risk probability of poor outcome entirely based on individual characteristics. However, to date, no nomogram models have been found to predict the probability of 6-month poor outcome after ischemic stroke. We aimed to develop and validate a nomogram for individualized prediction of the probability of 6-month unfavorable outcome in Chinese patients with ischemic stroke. Methods Based on the retrospective stroke registry, a single-center study which included 499 patients from May, 2013 to May, 2018 was conducted in Nanjing First Hospital (China) for ischemic stroke within 12 h of symptoms onset. The main outcome measure was 6-month unfavorable outcome (mRS > 2). To generate the nomogram, NIHSS score on admission, Age, previous Diabetes mellitus and crEatinine (NADE) were integrated into the model. We assessed the discriminative performance by using the area under the curve (AUC) of receiver-operating characteristic (ROC) and calibration of risk prediction model by using the Hosmer–Lemeshow test. Results A visual NADE nomogram was constructed that NIHSS score on admission (OR: 1.190, 95%CI: 1.125–1.258), age (OR: 1.068, 95%CI: 1.045–1.090), previous diabetes mellitus (OR: 1.995, 95%CI: 1.236–3.221) and creatinine (OR: 1.010, 95%CI: 1.002–1.018) were found to be significant predictors of 6-month unfavorable outcome after acute ischemic stroke in Chinese patients. The AUC–ROC of nomogram was 0.791. Calibration was good (p = 0.4982 for the Hosmer–Lemeshow test). Conclusion The NADE is the first nomogram developed and validated in Chinese ischemic stroke patients to provide an individual, visual and precise prediction of the risk probability of 6-month unfavorable outcome.

Additional file 1: Table S1. Demographics and clinical characteristics according to 6-month outcome.

Background Fractional flow reserve (FFR)-guided revascularization strategy is popular in coronary intervention. However, the feasibility of assessing stenotic severity in intracranial large arteries using pressure gradient measurements still remains unclear. Methods Between March 2013 and May 2014, 12 consecutive patients with intracranial large artery stenosis (including intracranial internal carotid artery, middle cerebral M1 segment, intracranial vertebral artery, and basilar artery) were enrolled in this study. The trans-stenotic pressure gradient was measured before and/or after percutaneous transluminal angioplasty and stenting (PTAS), and was then compared with percent diameter stenosis. A Pd/Pa cut-off of ≤0.70 was used to guide stenting of hemodynamically significant stenoses. The device-related and procedure-related serious adverse events and recurrent cerebral ischemic events were recorded. Results The target vessel could be reached in all cases. No technical complications occurred due to the specific study protocol. Excellent pressure signals were obtained in all patients. For seven patients who performed PTAS, the mean pre-procedural pressure gradient decreased from 59.0 ± 17.2 to 13.3 ± 13.6 mm Hg after the procedure (P

Objective: To investigate whether dual tissue-defined ischemic attacks, defined as multiple diffusion-weighted imaging lesions of different age and/or arterial territory (dual DWI), are an independent and stronger predictor of 90-day stroke than dual clinical TIAs (dual TIA). Methods: Consecutive patients with clinically defined TIA were enrolled and assessed clinically and by MRI within 3 days. The predictive ability of the ABCD clinical factors, dual TIA, and dual DWI was evaluated by means of multivariate logistic regression. Results: Among 658 patients who were included in the study and completed 90 days of follow-up, a total of 70 patients (10.6%) experienced subsequent stroke by 90 days. Multivariate logistic regression indicated that dual DWI was an independent predictor for subsequent stroke (odds ratio 4.64, 95% confidence interval 2.15–10.01), while dual TIA was not (odds ratio 1.18, 95% confidence interval 0.69–2.01). C statistics was higher when the item of dual TIA in ABCD3-I score was replaced by dual DWI (0.759 vs 0.729, p = 0.035). The net reclassification value for 90-day stroke risk was also improved (continuous net reclassification improvement 0.301, p = 0.017). Conclusion: Dual DWI independently predicted future stroke in patients with TIA. A new ABCD3-I score with dual DWI instead of dual clinical TIA may improve risk stratification for early stroke risk after TIA.

Ground source heat pump (GSHP) facilitates the efficient utilization of renewable energy sources and energy conservation, and it is expected to be more prevalent in the future for the great potential to substitute the use of renewable energy for burning of fossil fuels. As we all know, groundwater heat pump (GWHP) and aquifer thermal energy storage (ATES) are typical forms in the area of GSHP and underground thermal energy storage (UTES) respectively. The effect of energy conservation plays an important role in the national energy strategy, but the groundwater environment has been affected and even damaged to some extent because of over-exploitation and unreasonable utilization. This paper reviewed the development from GWHP to ATES worldwide, especially in China and surveyed the situation of groundwater utilization from GWHP. It shows that lack of cognitive ability, scientific constraints and reasonable utilization may bring catastrophic damage to the groundwater resource. Future work should aim at more research on basic problems during the demonstration of applications, such as thermal interaction between pumping and injecting wells, energy transport in the field of well, groundwater contamination, etc. In fact, the characteristics and performance of unsteady and transient heat transfer in the complex underground environment of multi-wells, and their control strategies of the GWHP and ATES systems have been also the most pressing problems. Their explorations and studies will strengthen the theoretical and practical understanding, and guide an orderly, healthy and sustainable development from GWHP to ATES technologies. (C) 2014 Elsevier Ltd. All rights reserved.

We propose a surface plasmon resonance (SPR) sensor based on phase modulation and polarization interferometry, both of which provide a refractive index (RI) resolution of the same order as that of SPR sensors of the phase type. And it has a wide dynamic range and insensitivity of RI resolution to the thickness of metal films as that of the intensity type SPR sensors. In this letter, we choose electro-optic (EO) phase modulation instead of the angle modulation. We demonstrate theoretically that with the EO phase modulation, our sensor could provide a better RI resolution.

In the thermal energy utilization of a closed loop groundwater system of a groundwater source heat pump (GWHP) and an aquifer thermal energy storage (ATES), thermal breakthrough always occurs. This problem causes a gradual variation in the temperature of the pumping water and impacts the efficiency of the GWHP. In particular, a large scale GWHP system requires many wells; thus, the well location and arrangement become a considerable technological challenge. The aim of this study is to develop a numerical model for groundwater systems to obtain a fair comparison of the energy efficiency between different well locations and arrangement modes. In this study, four typical modes are studied to determine the thermal interaction influences, and the numerical model was verified with test data by using an artificial rock/soil test system. The comparisons show good agreement between the numerical date and the measured data. It is shown that the temperature variation is related to the well arrangement mode, and the row arrangement of well groups may be a better choice. Therefore, a suitable spacing well pattern in the limited area is helpful and can potentially decrease the intensity of the thermal interaction and resist the occurrence of thermal breakthrough.

Comparison of lesion locations between patients with and without VCI after stroke. Data showed no between-group differences concerning the locations of acute and chronic brain lesions (effect sizes ranged from 0.02 to 0.40). (DOCX 15 kb)

To evaluate the effect of carotid angioplasty and stenting (CAS) on postoperative cerebrovascular reactivity (CVR) and its independent predictors.During July 2008 and September 2009, 37 patients undergone CAS were enrolled in this study. Breath holding tests using transcranial Doppler were performed for each patient before, 1 to 2 days, and 3 to 10 months after the procedure. CVR was evaluated by the breath holding index (BHI). Repeated measures analysis of variance was employed to detect the BHI changes after CAS. Multivariate linear regression was used to identify the independent predictors for BHI.A significant improvement of the ipsilateral BHI values was observed after stenting (P0.05). The follow-up BHI values were positively correlated with those after procedures (β = 1.030, P0.001), while negatively correlated with tandem stenoses (β = -0.016, P = 0.002).CAS results in an immediate improvement and a gradual normalization of the ipsilateral CVR. Tandem stenoses are an independent predictor for CVR.

Although several risk factors for prolonged length of stay (LOS) and increased hospital cost have been identified, the association between LOS, hospital cost, and neutrophil-to-lymphocyte ratio (NLR) has not yet been investigated. We aimed to investigate the influence of NLR on LOS and hospital cost in patients with acute ischemic stroke.Patients with acute ischemic stroke diagnosed within 24 hours of symptom onset were included. Univariate analysis and stepwise multiple regression analysis were used to identify independent predictors of LOS and hospital cost.A total of 346 patients were included in the final analysis. The median LOS was 11 days (range 8-13 days). The median acute hospital cost per patient was 19,030.6 RMB (U.S. $ 3065.8) (range 14,450.8 RMB-25,218.2 RMB). Neutrophil count to lymphocyte count (NLR) (P .001), diabetes mellitus (P = .034), stroke subtype (P = .005), and initial stroke severity (P .001) were significantly associated with prolonged LOS in the univariate analysis. NLR (P .001), smoking (P = .04), stroke subtype (P .001), initial stroke severity (P .001), and LOS (P .001) were significantly associated with increased hospital cost in the univariate analysis. Multivariate regression analysis showed that NLR was an independent predictor of both LOS and acute hospital cost. In addition, high NLR was significantly correlated with poor outcome at discharge, prolonged LOS, and increased hospital cost.NLR is significantly associated with LOS and acute hospital cost in patients presenting with acute ischemic stroke. It is a simple, inexpensive, and readily available biomarker and may serve as a clinically practical indicator for assessing the economic burden of stroke.

Background:Valid telephone assessment for cognitive impairment is lacking in stroke settings. We investigated the feasibility and validity of the 5-minute National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) protocol and six-item screener (SIS) in stroke patients by telephone administration.Methods:Patients were assessed with a comprehensive face-to-face neuropsychological assessment after three months of stroke onset, followed by the 5-minute NINDS-CSN protocol (30 points) and SIS (6 points) at least one month later. Administration time was recorded for the telephone tests. Validity of both tests was determined using the area under the receiver operating characteristics curve (AUC).Results:Eighty-nine patients (age, 62.9 ± 8.6 years; male, 65.2%) received a face-to-face assessment and 80 completed telephone tests. The time required to administer the 5-minute NINDS-CSN protocol was 4.3 ± 1.0 minutes, and SIS 57.3 ± 17.7 seconds. Validity of detecting cognitive impairment as assessed by AUC was 0.86 (95% CI, 0.78–0.94) for 5-minute NINDS-CSN protocol, and 0.74 (95% CI, 0.63–0.85) for SIS. Sensitivity and specificity were optimal with the cut-off values of 23.5/24 for the 5-minute NINDS-CSN protocol, and 4/5 for SIS.Conclusions:Both the telephone-based 5-minute NINDS-CSN protocol and SIS were feasible and valid in screening cognitive impairment after stroke in China.

Both adiponectin and endothelial progenitor cells (EPCs) have been proposed recently with anti-atherosclerosis effects. However, their impacts on vascular outcomes in patients with large artery atherosclerosis (LAA) are unclear. This study aimed to investigate the relationship between adiponectin, EPCs and stroke with a case-control design.The study cohort included 127 patients (61.3 ± 11.0 years; 73.2% men) with LAA stroke and 58 control subjects (60.9 ± 9.2 years; 70.7% men) referred for adiponectin and EPCs levels testing. We collected demographic, clinical, angiographical features, and laboratory data. Influence of adiponectin and EPCs levels on cerebral atherosclerosis and LAA stroke was analyzed with regression models.The levels of adiponectin and EPCs in atherosclerotic stroke patients were significantly lower compared with matched controls (p0.05). Logistic regression analysis identified that reduced levels of adiponectin and EPCs were closely correlated with cerebral atherosclerosis and LAA stroke. The associations remained significant after adjustment for age, sex and other confounders. Additionally, partial correlation analysis revealed a significant positive association between adiponectin and three subpopulations of EPCs levels (CD34(+)CD133(+)CD309(+)cells: r = 0.510, p = 0.001; CD34(+) CD133(-)CD309(+)cells: r = 0.262, p = 0.004; CD34(-)CD133(+)CD309(+)cells: r = 0.348, p0.001).Adiponectin is positively correlated with EPCs levels, and both of them are independently associated with LAA stroke.

We read with interest the article by Lisabeth et al1 comparing stroke outcomes in Mexican Americans and non-Hispanic whites. In this study, ethnical differences of stroke outcomes in 461 Mexican Americans and 259 non-Hispanic white patients were compared using Tobit or linear regression model. This letter is devoted to challenging their statistical application of the …