Toxin genotypes, antibiotic resistance and their correlations in Clostridioides difficile isolated from hospitals in Xi'an, China.

BACKGROUND: Clostridioides difficile is the main pathogen of antimicrobial-associated diarrhoea and health care facility-associated infectious diarrhoea. This study aimed to investigate the prevalence, toxin genotypes, and antibiotic resistance of C. difficile among hospitalized patients in Xi'an, China. RESULTS: We isolated and cultured 156 strains of C. difficile, representing 12.67% of the 1231 inpatient stool samples collected. Among the isolates, tcdA + B + strains were predominant, accounting for 78.2% (122/156), followed by 27 tcdA-B + strains (27/156, 17.3%) and 6 binary toxin gene-positive strains. The positive rates of three regulatory genes, tcdC, tcdR, and tcdE, were 89.1% (139/156), 96.8% (151/156), and 100%, respectively. All isolates were sensitive to metronidazole, and the resistance rates to clindamycin and cephalosporins were also high. Six strains were found to be resistant to vancomycin. CONCLUSION: Currently, the prevalence rate of C. difficile infection (CDI) in Xi'an is 12.67% (156/1231), with the major toxin genotype of the isolates being tcdA + tcdB + cdtA-/B-. Metronidazole and vancomycin were still effective drugs for the treatment of CDI, but we should pay attention to antibiotic management and epidemiological surveillance of CDI.

Analysis of Pediatric Surgical Disease Spectrum in a Tertiary Hospital.

Objective: To analyze the main disease composition of children hospitalized in pediatric surgery, explore the correlation between disease types and gender, and provide a reference for hospital management and pediatric disease prevention. Methods: Using ICD-10 codes as the classification standard for disease diagnosis, a statistical analysis was conducted on the disease composition of children hospitalized in the Pediatric Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from January 1, 2015, to December 31, 2015, followed by the establishment of a clinical database. A total of 1647 male patients and 817 female patients were enrolled in the study, resulting in a male-to-female ratio of 2:1. The age range of the patients spanned from 0 to 18 years, with a marked imbalance in patient distribution among the various age groups. Statistical analysis was conducted using SPSS version 18.0 software. A chi-square test was performed to analyze the differences in the composition of disease systems and the composition of major diseases in terms of sex and age. Results: Pediatric patients were admitted with complex and diverse diseases in 2015, involving 15 systems of the human body and 400 diseases. Digestive system diseases, tumors, congenital malformations, and genitourinary system diseases were the top four diseases accounting for 83.5% of all pediatric cases. 561 patients were aged 0 years, accounting for 22.3% of all cases, while 1,801 patients fell within the 0-5 years age group, constituting 73.1% of the total. The differences in disease system composition among different sex and age groups of pediatric surgical inpatients were statistically significant (P = .001). There are statistically significant differences in the length of hospital stay and hospitalization costs among pediatric surgical inpatients in different age groups (P = .001). Conclusion: To strengthen the diagnosis and treatment of pediatric surgical diseases, we should strengthen the construction of key departments, optimize the consultation process according to the characteristics of children's disease spectrum, and improve the level of diagnosis and treatment of pediatric surgical diseases.

Association between different acute stroke therapies and development of post stroke seizures.

BACKGROUND: Epilepsy is a major complication of stroke. We aimed to establish whether there is an association between intravenous thrombolysis, intra-arterial thrombolysis and post stroke seizure (PSS) development. Improved understanding of the relationship between reperfusion therapies and seizure development may improve post-stroke monitoring and follow-up. METHODS: This was a retrospective, multicentre cohort study conducted at the Royal Melbourne Hospital and Jingling Hospital Nanjing. We included patients with anterior circulation ischemic stroke admitted 2008-2015. Patients were divided into four treatment groups 1. IV-tPA only, 2. Intra-arterial therapies (IAT) only, 3. IAT + IV-tPA and 4. stroke unit care only (i.e. no IV-tPA or IAT). To assess the association between type of reperfusion treatment and seizure incidence we used multivariable logistic regression models adjusted for age, stroke severity, 3-month functional outcome and prognostic factors. RESULTS: There were 1375 stroke unit care-only patients, of whom 28 (2%) developed PSS. There were 363 patients who received only IV-tPA, of whom 21 (5.8%) developed PSS. There were 93 patients who received IAT only, of whom 12 (12.9%) developed PSS and 112 that received both IV-tPA + IAT, of which 5 (4.5%) developed PSS. All reperfusion treatments were associated with seizure development compared to stroke unit care-only patients: IV-tPA only adjusted odds ratio (aOR) 3.7, 95%CI 1.8-7.4, p < 0.0001; IAT aOR 5.5, 95%CI 2.1-14.3, p < 0.0001, IAT + IV-tPA aOR 3.4, 95% CI 0.98-11.8, p = 0.05. These aORs did not differ significantly between treatment groups (IV-tPA + IAT versus IV-tPA p = 0.89, IV-tPA + IAT versus IAT, p = 0.44). CONCLUSIONS: Patients receiving thrombolytic or intra-arterial reperfusion therapies for acute ischemic stroke are at higher risk of epilepsy and may benefit from longer follow-up. No evidence for an additive or synergistic effect of treatment modality on seizure development was found.

The Association Between Atrial Fibrillation and Poststroke Seizures is Influenced by Ethnicity and Environmental Factors.

GOAL: Epilepsy is a major complication of stroke. There have been suggestions that patients with cardioembolic stroke are at a greater risk of developing seizures than other stroke subtypes. However, the incidence of atrial fibrillation (AF) and cardioembolic stroke varies considerably across countries, generally higher in Western populations than in Asian populations. This study assessed whether ethnicity affects the association between AF and poststroke seizure (PSS) development. We hypothesized that Royal Melbourne Hospital ([RMH] Melbourne) patients will have significantly higher incidence of AF-related PSS than in the Jinling Hospital (Nanjing) population. MATERIALS AND METHODS: This was a retrospective, multicenter cohort study including patients with anterior circulation ischemic stroke admitted between 2008 and 2015. Occurrences of PSS were ascertained by reviewing medical records or telephone follow-up. To test the hypothesis of an interaction between ethnicity and AF for PSS occurrence, a logistic regression model with AF and ethnicity together with an ethnicity-by-AF interaction term was used. FINDINGS: Of 782 patients followed-up for seizure development at RMH, 247 (31.6%) patients had AF, of whom 10 (4%) developed PSS. Of 1185 patients followed-up and included at JH, 54 (4.8%) patients with AF, of whom 4 (7.4%) developed PSS. At RMH, no significant association was found between AF and PSS; odds ratio .75, 95% confidence interval .4-1.6, (P = .4). At JH, there was a significant association between AF and increased PSS: OR 4.0, 95% CI 1.3-12.1, (P = .01), P for interaction = .03. CONCLUSION: Further understanding of genetic risks and environmental differences across ethnic populations and the role in PSS is required.

Opposite roles of bradykinin B1 and B2 receptors during cerebral ischaemia-reperfusion injury in experimental diabetic rats.

Bradykinin receptors play important roles in cerebral ischaemia-reperfusion (I/R) injury of non-diabetics. Their functions in diabetics, however, have not been studied. In this study, we hypothesized that bradykinin 1 receptor (B1R) and bradykinin 2 receptor (B2R) would be upregulated and participate in the regulation of diabetic ischaemic stroke. To investigate this, we first evaluated B1R and B2R expression at different time points after I/R in non-diabetic and diabetic rats (Sprague-Dawley) by using real-time quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence. Then, pharmacological inhibitors were separately administered via the tail vein to analyse their effects on cerebral ischaemia in diabetics. Both receptors were significantly upregulated after cerebral I/R in non-diabetic and diabetic rats. B1R expression in diabetic rats increased in a sharper manner than in non-diabetic rats, whereas B2R expression increased to the same level during the early stage of reperfusion but later became lower. Interestingly, the upregulated B1R was expressed in astrocytes, whereas B2R was mainly located in neurons in the ischaemic penumbra. Functional studies showed that inhibition of B1R significantly reduced infarct volume, neurological deficits, cell apoptosis, and neuron degeneration, probably by attenuating blood-brain barrier (BBB) disruption and post-ischaemic inflammation, at 24 h after reperfusion. In contrast, B2R antagonist had opposite effects, and exacerbated BBB penetrability and tissue inflammation. These findings suggest that B1R and B2R have detrimental and beneficial effects, respectively in diabetic cerebral ischaemia, which might open new avenues for the treatment of ischaemic stroke in diabetic patients through selective pharmacological blockade or activation.

Variant recurrent risk among stroke patients with different CYP2C19 phenotypes and treated with clopidogrel.

Polymorphisms of CYP2C19 have been associated with variant risk of subsequent cardiovascular events in survivors of myocardial infarction (MI) receiving clopidogrel. This study evaluated the impacts of CYP2C19 polymorphisms on stroke recurrence and other vascular events in a cohort of Chinese patients receiving clopidogrel. From Nanjing Stroke Registry Program, 625 consecutive patients with ischemic stroke were enrolled between May 2008 and April 2010. CYP2C19 variants (*2, *3, and *17) were genotyped. Clinical outcomes were determined with three monthly follow-up. The primary endpoint was a composite of vascular death, non-fatal ischemic stroke, and non-fatal MI. The second endpoint was bleeding events. The median exposure to clopidogrel was 13.2 (interquartile range, 8.9-18.0) months. Primary endpoint was observed in 85 (13.6%) patients and secondary endpoint in 13 (2.1%) patients. Frequencies of CYP2C19*1, *2, *3, and *17 alleles were 61.2, 34.0, 3.8, and 1.0%, respectively, in this patient cohort. CYP2C19 loss-of-function allele (*2 and *3, LOF) carriers were observed with higher risk of subsequent vascular events compared with non-carriers (17.2 versus 8.1%, HR = 2.16, 95% CI: 1.31-3.56, p = 0.003). After adjusted for age, sex, major cardiovascular risk factors, and drug agent, CYP2C19 LOF carrier was independently associated with primary endpoint (HR = 2.31, 95% CI: 1.39-3.84, p = 0.001). No significant association between CYP2C19 gain-of-function (*17, GOF) and clinical events was detected. In Chinese stroke survivors treated with clopidogrel, carriers of CYP2C19 LOF allele may have increased risk of recurrence.

Comparison of carotid and cerebrovascular stenosis between diabetic and nondiabetic patients using digital subtraction angiography.

BACKGROUND: The aim of our study was to evaluate the differences of prevalence and manifestation of extracranial and intracranial artery stenosis between patients with and without type 2 diabetes using digital subtraction angiography. METHODS: A retrospective study was conducted by analyzing clinical and lifestyle data collected from 1137 patients enrolled in the Nanjing Stroke Registry Program between June 2004 and March 2011. Vascular risk factors were analyzed, and carotid and cerebrovascular artery stenoses were measured in 383 patients with type 2 diabetes mellitus and 754 nondiabetic patients by digital subtraction angiography. RESULTS: In all, 1069 stenoses were found among 383 diabetic patients and 1990 among 754 nondiabetic patients. No statistical differences were observed for the distribution of stenosis in intracranial-extracranial vessels between diabetic and nondiabetic patients (P=.210). There was no difference in the distribution of stenosis in the anterior and posterior circulation vessels between these 2 groups (P=.628). Among diabetic patients with stenosis, a single stenosis was found in 116 (30.29%) and multiple stenoses were found in 267 (69.71%). In their nondiabetic counterparts, a single stenosis was found in 249 (33.02%) and multiple stenoses were found in 505 (66.98%). Compared with nondiabetic patients, the diabetic patients have a tendency of a higher incidence of multiple stenosis. Nonobstructive stenosis occurs more often in diabetic than in nondiabetic patients (P=.002). CONCLUSIONS: This retrospective study suggests that diabetes be associated with higher incidence of nonobstructive stenosis and that there be no significant difference observed in the extent and distribution of the extra- and intracranial artery stenoses between diabetic and nondiabetic patients.

[Intranasal dosing of nerve growth factor protects brain from poisoning of organophosphorus compounds in rats].

OBJECTIVE: To explore the protective effects of intranasal (IN) dosing of nerve growth factor (NGF) on brain injury induced by organophosphorus compounds (OP) in rats. METHODS: The OP-treated Sprague-Dawley rats received an intraperitoneal injection of atropine sulphate and pralidoxime at 1 min after intoxication. Then NGF or saline was dosed via the olfactory pathway. All rats were sacrificed 24 hours after OP exposure. Damaged nerve cells were estimated on corpus striatum strained with hematoxylin-eosin (H&E) method. And the activity of acetylcholinesterase (AchE) and the concentrations of malondialdehyde (MDA) and reduced glutathione hormone (GSH) in corpus striatum were measured by colorimetric method. RESULTS: As assessed by H&E staining, a large number of degenerated and necrotic nerve cells were observed in corpus striatum in rats from in IN saline group. But in IN NGF group, the number of degenerated neurons was smaller than in IN NS group. Following OP exposure, the activity of AchE decreased in corpus striatum in both IN saline and IN NGF groups (0.46 ± 0.11 vs 0.35 ± 0.09 U/mg prot). No significant differences existed between two groups. But the concentrations of MDA in corpus striatum of IN NGF group rats reduced markedly by 25.14% (4.02 ± 0.85 vs 5.37 ± 1.33 nmol/mg prot) and the level of GSH increased sharply by 15.73% (52.82 ± 2.80 vs 45.64 ± 4.88 mg/g prot) as compared with IN saline group (P < 0.05). CONCLUSION: Intranasal dosing of NGF may improve neuropathology and protect rats against OP-induced oxidative damage in corpus striatum.

Ferroptosis and traumatic brain injury.

Traumatic brain injury (TBI) is a worldwide health problem contributing to significant economic burden. TBI is difficult to treat partly due to incomplete understanding of pathophysiology. Ferroptosis is a type of iron-dependent programmed cell death which has gained increasing attention due to its possible role in TBI. Current studies have demonstrated that ferroptosis is related to the pathology of TBI, and inhibition of ferroptosis may improve long term outcomes of TBI. Therefore, clarification of the exact association between ferroptosis and traumatic brain injury is necessary and may provide new targets for treatment. This review describes (1) the ferroptosis pathways following traumatic brain injury, (2) the role of ferroptosis during the chronic phase of traumatic brain injury, and (3) potential therapies targeting the ferroptosis pathways.

Insulin enhances neointimal hyperplasia following arterial injury through the PI3K/Akt pathway in type 1 diabetic rats.

Although insulin is known to affect neointimal hyperplasia via distinct signaling pathways, how neointimal hyperplasia is affected in insulin­deficient type 1 diabetes remains unknown. The aim of the current study was to investigate two major signaling branches of insulin action regulating neointimal hyperplasia following arterial injury in type 1 diabetes with or without exogenous insulin administration. Rats were treated with vehicle (control group), streptozotocin (STZ) alone (STZ group; uncontrolled type 1 diabetes) or STZ followed by insulin (STZ + I group; controlled type 1 diabetes). Subsequently, a type 1 diabetic rat model of carotid artery balloon injury was established. Following this, the intima­to­media area ratios were examined for evidence of neointimal hyperplasia in the carotid arteries of the rats by performing hematoxylin­eosin staining. Furthermore, the protein expression of extracellular signal­regulated kinase (ERK), phosphorylated (p­) ERK, protein kinase B (Akt) and p­Akt in the carotid arteries of the rats was determined via immunoblotting. Moreover, an in vitro model of type 1 diabetes was induced by incubation of primary vascular smooth muscle cells (VSMCs) with glucose and/or insulin. Cellular proliferation and signaling protein expression levels in VSMCs were determined by measuring the incorporation of tritiated thymidine and performing immunoblotting, respectively. The results demonstrated that compared with that in control rats, neointimal hyperplasia and expression of p­Akt in uncontrolled type 1 diabetic rats were significantly decreased. This decrease was recovered in controlled type 1 diabetes with insulin therapy. Furthermore, the difference in the expression of p­ERK between groups was not significant. Additionally, the results of the cell experiments were consistent with those from the animal studies. In conclusion, the preferential signaling along the phosphatidylinositol 3­kinase/Akt pathway of insulin action in response to insulin restoration may contribute to neointimal hyperplasia. The present study provides a novel approach for the further treatment of neointimal hyperplasia in type 1 diabetes.

Intranasal delivery of transforming growth factor-beta1 in mice after stroke reduces infarct volume and increases neurogenesis in the subventricular zone.

BACKGROUND: The effect of neurotrophic factors in enhancing stroke-induced neurogenesis in the adult subventricular zone (SVZ) is limited by their poor blood-brain barrier (BBB) permeability.Intranasal administration is a noninvasive and valid method for delivery of neuropeptides into the brain, to bypass the BBB. We investigated the effect of treatment with intranasal transforming growth factor-beta1 (TGF-beta1) on neurogenesis in the adult mouse SVZ following focal ischemia. The modified Neurological Severity Scores (NSS) test was used to evaluate neurological function, and infarct volumes were determined from hematoxylin-stained sections. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) labeling was performed at 7 days after middle cerebral artery occlusion (MCAO). Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) and neuron- or glia-specific markers for identifying neurogenesis in the SVZ at 7, 14, 21, 28 days after MCAO. RESULTS: Intranasal treatment of TGF-beta1 shows significant improvement in neurological function and reduction of infarct volume compared with control animals. TGF-beta1 treated mice had significantly less TUNEL-positive cells in the ipsilateral striatum than that in control groups. The number of BrdU-incorporated cells in the SVZ and striatum was significantly increased in the TGF-beta1 treated group compared with control animals at each time point. In addition, numbers of BrdU- labeled cells coexpressed with the migrating neuroblast marker doublecortin (DCX) and the mature neuronal marker neuronal nuclei (NeuN) were significantly increased after intranasal delivery of TGF-beta1, while only a few BrdU labeled cells co-stained with glial fibrillary acidic protein (GFAP). CONCLUSION: Intranasal administration of TGF-beta1 reduces infarct volume, improves functional recovery and enhances neurogenesis in mice after stroke. Intranasal TGF-beta1 may have therapeutic potential for cerebrovascular disorders.

Depressed TSH level as a predictor of poststroke fatigue in patients with acute ischemic stroke.

OBJECTIVE: To investigate whether thyroid function profiles can predict poststroke fatigue (PSF) in patients with acute ischemic stroke. METHODS: Patients with stroke were consecutively recruited within 3 days of onset in Jinling Hospital. Serum levels of thyroid hormones, thyroid antibodies, hematologic indexes, and biochemical indexes were measured on admission. Fatigue was scored using the Fatigue Severity Scale. Associations were analyzed with multivariate regression and restricted cubic splines. RESULTS: Of the 704 patients with stroke, 292 (41.5%) were diagnosed with fatigue in the acute stage and 224 (35.3%) 6 months after the index stroke. The serum levels of thyroid-stimulating hormone (TSH) were inversely associated with the risk of PSF in both the acute phase and at follow-up evaluations after adjusting for potential confounders (odds ratio 0.30, 95% confidence interval 0.24-0.37 in the acute phase, and odds ratio 0.70, 95% confidence interval 0.58-0.84 at follow-up). The subgroup analysis indicated that in the acute phase of ischemic stroke, TSH was associated with severity of PSF in the groups with euthyroidism (ß = -0.70, p < 0.001), subclinical hypothyroidism (ß = -0.44, p < 0.001), and low-T3 syndrome (ß = -0.34, p = 0.008). Higher TSH was associated with better Fatigue Severity Scale scores in patients with low-T3 syndrome 6 months after the index stroke (ß = -0.35, p = 0.01). Furthermore, in the group with low-T3 syndrome, FT3 serum level could also indicate a higher risk of PSF (ß = -2.54, p < 0.001 in the acute phase, and ß = -2.67, p < 0.001 at follow-up). CONCLUSION: Thyroid function profiles may predict fatigue after acute ischemic stroke, suggesting that neuroendocrine responses could have a role in PSF.

Intranasally delivered TGF-beta1 enters brain and regulates gene expressions of its receptors in rats.

This study is aimed to evaluate the brain distribution of transforming growth factor-beta1 (TGF-beta1) following intranasal administration and the subsequent biological effects of TGF-beta1. Adult rats were given recombinant human TGF-beta1 (rhTGF-beta1) or vehicle solution intranasally. TGF-beta1 concentrations were significantly raised in several brain regions and the trigeminal nerve following intranasal delivery. The elevation appeared within 30 min and was sustained for at least 6 h, reaching its greatest level at 60 min. A concentration gradient in the central nervous system (CNS) regions was produced during the first 2 h after intranasal administration, with the OB presenting a significantly higher concentration than any other CNS regions. The nasally administered TGF-beta1 subsequently regulated gene expressions of its two receptors (TGF-beta receptor types I and II) in vivo, but did not affect mRNA level of TGF-beta1 itself. Our results suggest that TGF-beta1 can be transported into the CNS via the olfactory and trigeminal pathways, and may consequently exert its biological effects by regulating gene expressions of its receptors. Intranasal administration of neurotrophic factors may offer a potential strategy for treating some CNS disorders.

Early Increased Bradykinin 1 Receptor Contributes to Hemorrhagic Transformation After Ischemic Stroke in Type 1 Diabetic Rats.

Hemorrhagic transformation (HT) is a major complication of ischemic stroke and further deteriorates neurological outcomes. Bradykinin 1 receptor (B1R) has been proven to mediate vasculo-toxicity in various experimental models. However, its role in the development of HT after stroke remains unclear. We detected the B1R expression in brain tissues with or without HT in a rat model of cerebral ischemia/reperfusion (I/R) with type 1 diabetes, showing higher B1R expression in the hemorrhagic areas than the ischemic tissues. Then, B1R agonist or antagonist was administrated intravenously just before reperfusion to investigate its effect on HT and the underlying molecular mechanism. Administration of low (300 nmol/kg) or high (1 µmol/kg) dose of B1R antagonist mitigated hemorrhage, improved neurobehavioral deficits, and preserved blood-brain-barrier (BBB) integrity after reperfusion for 8 h whereas the 300 nmol/kg of B1R agonist aggravated these outcomes, though only the high does of B1R antagonist affected the infarction volume. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was increased by B1R activation but decreased by B1R inhibition, which mediated B1R toxicity on BBB disruption and ischemia-related HT. Furthermore, B1R activation facilitated the mRNA and protein expressions of MMP-9 in the hemorrhagic tissues, and these increases were blocked by both ERK inhibitor U0126 and NF-κB inhibitor PDTC. U0126 also remarkably decreased the B1R-induced NF-κB/p65 activation. We concluded that upregulated B1R may contribute to early HT after I/R in type 1 diabetic rats via ERK1/2/NF-κB/MMP-9 pathway. B1R inhibition could be an encouraging therapeutic strategy to withstand HT after ischemic stroke in diabetic patients.

Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack.

Rationale Paroxysmal atrial fibrillation is a common and preventable cause of devastating strokes. However, currently available monitoring methods, including Holter monitoring, cardiac telemetry and event loop recorders, have drawbacks that restrict their application in the general stroke population. AliveCor™ heart monitor, a novel device that embeds miniaturized electrocardiography (ECG) in a smartphone case coupled with an application to record and diagnose the ECG, has recently been shown to provide an accurate and sensitive single lead ECG diagnosis of atrial fibrillation. This device could be used by nurses to record a 30-s ECG instead of manual pulse taking and automatically provide a diagnosis of atrial fibrillation. Aims To compare the proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring with current standard practice. Sample size 296 Patients. Design Consecutive ischemic stroke and transient ischemic attack patients presenting to participating stroke units without known atrial fibrillation will undergo intermittent AliveCor™ ECG monitoring administered by nursing staff at the same frequency as the vital observations of pulse and blood pressure until discharge, in addition to the standard testing paradigm of each participating stroke unit to detect paroxysmal atrial fibrillation. Study outcome Proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring compared to 12-lead ECG, 24-h Holter monitoring and cardiac telemetry. Discussion Use of AliveCor™ heart monitor as part of routine stroke unit nursing observation has the potential to be an inexpensive non-invasive method to increase paroxysmal atrial fibrillation detection, leading to improvement in stroke secondary prevention.

Healable and Optically Transparent Polymeric Films Capable of Being Erased on Demand.

Different from living organisms, artificial materials can only undergo a limited number of damage/healing processes and cannot heal severe damage. As an alternative to solve this problem, we report in this study the fabrication of erasable, optically transparent and healable films by exponential layer-by-layer assembly of poly(acrylic acid) (PAA) and poly(ethylene oxide) (PEO). The hydrogen-bonded PAA/PEO films are highly transparent, capable of conveniently healing damages and being erased under external stimuli. The PAA/PEO films can heal damages such as scratches and deep cuts for multiple times in the same location by exposure to pH 2.5 water or humid N2 flow. The healability of the PAA/PEO films originates from the reversibility of the hydrogen bonding interaction between PAA and PEO, and the tendency of films to flow upon adsorption of water. When the damage exceeds the capability of the films to repair, the damaged films can be conveniently erased from substrates to facilitate the replacement of the damaged films with new ones. The combination of healability and erasibility provides a new way to the design of transparent films with enhanced reliability and extended service life.

Caveolae: molecular insights and therapeutic targets for stroke.

INTRODUCTION: Caveolae are specialized plasma membrane micro-invaginations of most mammalian cell types. The organization and function of caveolae are carried out by their coat proteins, caveolins and adaptor proteins, cavins. Caveolae/caveolins physically interact with membrane-associated signaling molecules and function in cholesterol incorporation, signaling transduction and macromolecular transport/permeability. AREAS COVERED: Recent investigations have implicated a check-and-balance role of caveolae in the pathophysiology of cerebral ischemia. Caveolin knockout mice displayed exacerbated ischemic injury, whereas caveolin peptide exerted remarkable protection against ischemia/reperfusion injury. This review attempts to provide a comprehensive synopsis of how caveolae/caveolins modulate blood-brain barrier permeability, pro-survival signaling, angiogenesis and neuroinflammation, and how this may contribute to a better understanding of the participation of caveolae in ischemic cascade. The role of caveolin in the preconditioning-induced tolerance against ischemia is also discussed. EXPERT OPINION: Caveolae represent a novel target for cerebral ischemia. It remains open how to manipulate caveolin expression in a practical way to recapitulate the beneficial therapeutic outcomes. Caveolin peptides and associated antagomirs may be efficacious and deserve further investigations for their potential benefits for stroke.

Cerebral arteriostenosis associated with elevated serum-immunoglobulin E level in young adults without risk factors for ischemic stroke: a possible manifestation of cerebral vasculitis?

We report a series of young adults with symptomatic cerebral arteriostenosis characterized by elevated serum immunoglobulin (Ig) E levels. All patients had no definite risk factors for cerebral vascular diseases. The clinical data of 26 young adults (age 18-50 years) with ischemic stroke, characterized only by increased serum IgE levels and without risk factors for cerebral vascular disease, were retrospectively reviewed. Arteriostenosis was surveyed and followed-up by digital subtraction angiography (DSA), and the stenosis rate was estimated using the warfarin-aspirin symptomatic intracranial disease technique. All patients were treated with corticosteroids according to the common strategy for vasculitis. There was no recurrent stroke during follow-up. The mean degree of stenosis before and after treatment was 69.3±29.8% and 47.9±45.1%, respectively. The difference of stenosis rates between initial and follow-up DSA evaluation was significant using a paired samples test (21.31±26.88, 95% confidence interval [CI] 13.58-29.03, t=5.55, p<0.001). Kaplan-Meier survival analysis revealed that the 13-month cumulative improved lesion rate was 40.3±8.7%. This remained the same at 18 months. The mean time to lesion improvement was 12.58 ± 0.96 months (95% CI 10.70-14.46) and median time was 13±3.88 months (95% CI 5.39-20.61). To our knowledge, cerebral arteriostenosis with only elevated IgE serum levels has not been reported. Our data showed that corticosteroid treatment can achieve clinical and artery improvement. This suggests that the cerebral arteriostenosis seen in our study might be caused by some specific type of vessel inflammation.

Intranasal nerve growth factor attenuates tau phosphorylation in brain after traumatic brain injury in rats.

Traumatic brain injury (TBI) is a considerable cause of mild cognitive impairment and dementia. Intranasal administration of nerve growth factor (NGF) has previously been found to improve cognitive function after TBI, but the mechanism remains unclear. This study aimed to investigate the effects of intranasal NGF on the tau hyperphosphorylation following TBI. A modified Feeney's weight-drop model was used to induce TBI. Rats were randomly divided into control group, TBI group, TBI+NGF group, TBI+PDTC group and TBI+IL-1ra group. Rats in TBI+NGF group were administered with NGF (5 µg/d) for 3d before surgery. Hyperphosphorylated tau protein was remarkable in the peri-contusional cortex area with TBI. Both western blotting and immunostaining results displayed intranasal pretreatment of NGF significantly reduced tau phosphorylation. To evaluate the underlying mechanism, the levels of glycogen synthase kinase 3ß (GSK-3ß), interleukin-1ß (IL-1ß), and the DNA binding activity of nuclear factor-κB (NF-κB) were assayed. NGF markedly inhibited GSK-3ß. NGF also reduced TBI-induced elevation of IL-1ß and NF-κB DNA binding activity. Furthermore, PDTC and IL-1ra were injected to prove a potential signaling pathway among NF-κB, IL-1ß and GSK-3ß. Taken together, these findings demonstrated that intranasal NGF could effectively attenuate the hyperphosphorylation of tau after TBI, which might involve an integrated signaling pathway related to NF-κB.

Pattern of cerebrovascular atherosclerotic stenosis in older Chinese patients with stroke.

The clinical pattern and angiographic distribution of cerebral atherosclerosis varies among different ethnic groups. This study was designed to identify the clinical background for intracranial and extracranial atherosclerotic stenosis in older eastern Chinese patients using digital subtraction angiography. We retrospectively reviewed the data collected from the Nanjing Stroke Registry Program, from January 2004 to March 2011. The analysis focused on the intracranial or extracranial location of stenosis in the anterior and posterior circulations. In total, records of 1041 patients were included in the study. Of these patients, 19.88% had intracranial carotid stenosis, 18.73% had stenosis in the extracranial vessels, and 33.33% had concurrent stenoses. A total of 2002 stenotic sites were detected in 749 patients. Among those patients with stenosis, a single stenosis was found in 170 (16.33%) and multiple stenoses were found in 579 (55.62%). The prevalence of intracranial stenosis in the single-stenosis group was 54.12%, while in the multiple-stenosis group it was 47.87% (p=0.127). A higher incidence of severe stenosis (70-99% blockage) and occlusion was found in the intracranial vessels than in the extracranial vessels (p=0.018). Older Chinese patients with atherosclerotic stenosis tend to have more intracranial stenoses.