Anti-neuron antibody syndrome: clinical features, cytokines/chemokines and predictors.

BACKGROUND: Neuroimmunology is a rapidly expanding field, and there have been recent discoveries of new antibodies and neurological syndromes. Most of the current clinical studies have focused on disorders involving one specific antibody. We have summarized a class of antibodies that target common neuronal epitopes, and we have proposed the term "anti-neuron antibody syndrome" (ANAS). In this study, we aimed to clarify the clinical range and analyse the clinical features, cytokines/chemokines and predictors in ANAS. METHODS: This was a retrospective cohort study investigating patients with neurological manifestations that were positive for anti-neuron antibodies. RESULTS: A total of 110 patients were identified, of which 43 patients were classified as having autoimmune encephalitis (AE) and the other 67 were classified as having paraneoplastic neurological syndrome (PNS). With regards to anti-neuron antibodies, 42 patients tested positive for anti-N-methyl-D-aspartate receptor (NMDAR) antibody, 19 for anti-Hu, 14 for anti-Yo and 12 for anti-PNMA2 (Ma2). There were significant differences between the ANAS and control groups in serum B cell-activating factor (BAFF) levels and in cerebrospinal fluid (CSF) C-X-C motif chemokine10 (CXCL10), CXCL13, interleukin10 (IL10), BAFF and transforming growth factor ß1 (TGFß1) levels. Predictors of poor outcomes included having tumours (P = 0.0193) and having a chronic onset (P = 0.0306), and predictors of relapses included having lower levels of CSF BAFF (P = 0.0491) and having a larger ratio of serum TGFß1/serum CXCL13 (P = 0.0182). CONCLUSIONS: Most patients with ANAS had a relatively good prognosis. Having tumours and a chronic onset were both associated with poor outcomes. CSF BAFF and the ratio of serum TGFß1/serum CXCL13 were associated with relapses.

Retrospective study of paraneoplastic neurological syndromes in a Chinese Han population from Shandong, East China.

OBJECTIVE: To analyze the clinical features, diagnostic strategies and therapeutic methods associated with paraneoplastic neurological syndromes. METHODS: A retrospective study of paraneoplastic neurological syndromes was performed at a single center in Shandong, East China. The medical records and follow-up data of 28 patients were intensively reviewed between February 2011 and December 2014. RESULTS: Twenty-four (85.7%) patients experienced subacute or chronic onset of disease, and the most common symptoms reported were mild myasthenia and paresthesias. Twenty-five (89.3%) patients presented nervous system lesions prior to occult tumors, and the median time frame between paraneoplastic neurological syndromes onset and the diagnosis of a tumor was 15 weeks. Sensorimotor neuropathy, Lambert-Eaton myasthenic syndrome and limbic encephalitis were the three most common neurological syndromes reported. Elevated serum tumor markers were observed in 44.0% of patients, while 40.7% of patients were positive for onconeural antibodies. Tumors were detected in 21 (75.0%) patients after repeated whole-body screening, and lung carcinomas were the most common primary tumor detected. Seventeen patients received anti-tumor or immunological therapy, and clinical symptoms were relieved in 13 (76.5%) of these patients. CONCLUSIONS: In the majority of paraneoplastic neurological syndromes patients, the onset of disease is subacute or chronic with mild clinical symptoms. Nervous system lesions usually occur prior to occult tumors with complicated and various clinical manifestations. Neither tumor markers nor onconeural antibodies exhibit a high rate of occurrence, while repeated whole-body screening is helpful in identifying occult tumors. Early diagnosis and treatment are crucial to these patients.

Degradation of p-Nitrophenol on Biochars: Role of Persistent Free Radicals.

Generation of environmentally persistent free radicals (EPFRs) on solid particles has recently attracted increasing research interest. EPFRs potentially have high reactivity and toxicity. However, the impact of EPFRs on organic contaminant behavior is unclear. We hypothesized that EPFRs in biochars can degrade organic contaminants and play an important role in organic contaminant behavior. We observed obvious degradation of p-nitrophenol (PNP) in the presence of biochars, through the detection of NO3(-) as well as organic byproducts. The extent of PNP degradation was correlated to the intensity of EPR signals of biochar particles. tert-Butanol (a •OH scavenger) did not completely inhibit PNP degradation, indicating that •OH could not fully explain PNP degradation. The decreased PNP degradation after tert-butanol addition was better correlated with reduced PNP sorption on biochars. PNP degradation through the direct contact with EPFRs in biochar particles could be an important contribution to the PNP concentration reduction in the aqueous phase. The coating of natural organic matter analogue (tannic acid) on biochars did not considerably inhibit PNP degradation, suggesting the ability of biochars to degrade PNP in soil and natural water. Similar EPFR-promoted degradation was observed for five different types of biochars and one activated carbon, as well as one additional chemical (p-aminophenol). Therefore, organic chemical degradation by EPFRs in biochars can be a common process in the environment and should be incorporated in organic chemical fate and risk studies.

Detecting free radicals in biochars and determining their ability to inhibit the germination and growth of corn, wheat and rice seedlings.

Biochar can benefit human society as a carbon-negative material and soil amendment. However, negative biochar impacts on plant germination and growth have been observed, and they have not been fully explained. Therefore, protocols to avoid these risks cannot be proposed. We hypothesized that the free radicals generated during charring may inhibit plant germination and growth. Significant electron paramagnetic resonance (EPR) signals were observed in the biochars derived from several types of common biomass (corn stalk, rice, and wheat straws) and the major biopolymer components of biomass (cellulose and lignin), but not in the original materials, suggesting the ubiquitous presence of free radicals in biochars. EPR signal intensity increased with increasing pyrolysis temperature, and it was dominantly contributed by oxygen centered in the mixture of oxygen- and carbon-centered free radicals as the temperature increased. The free radicals in biochars induced strong ·OH radicals in the aqueous phase. Significant germination inhibition, root and shoot growth retardation and plasma membrane damage were observed for biochars with abundant free radicals. Germination inhibition and plasma membrane damage were not obvious for biochars containing low free radicals, but they were apparent at comparable concentrations of conventional contaminants, such as heavy metals and polyaromatic hydrocarbons. The potential risk and harm of relatively persistent free radicals in biochars must be addressed to apply them safely.

Simultaneous catalytic oxidation of Hg0 and AsH3 over Fe-Ce co-doped TiO2 catalyst under low temperature and reducing atmosphere.

The Fe-Ce bimetal oxide-doped titanium dioxide composite was synthesized by the sol-gel method and the performance of the catalyst was investigated for the removal of Hg0 and AsH3 from yellow phosphorus flue gas under different conditions. Brunauer-Emmett-Teller (BET) analysis, high-resolution transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were used to characterize the crystal structure and morphology of the structure, and the mechanisms for removing Hg0 and AsH3 from flue gas by catalytic oxidation were deduced. The results showed that the optimal calcination temperature of the Fe5Ce5Ti catalyst was 500 °C, and the optimal pH of the sol was 6. Under these conditions, the penetration adsorption capacity of the Fe5Ce5Ti catalyst for the removal of AsH3 and Hg0 was 385.5 mg g-1 and 2.178 mg g-1, respectively. According to characterization analysis, Fe and Ce are the main active components in the removal of Hg0 and AsH3, and the mixed oxides of Fe and Ce have a synergistic effect on the surface of the mixed oxide-doped catalyst, which can improve the dispersion of the active component on the surface of the catalyst, and then improve the removal efficiency of Hg0 and AsH3.

Vascular endothelial growth factor improves the cognitive decline of Alzheimer's disease via concurrently inducing the expression of ADAM10 and reducing the expression of ß-site APP cleaving enzyme 1 in Tg2576 mice.

Alzheimer's disease (AD) is primarily characterized by the production and deposit of ß-amyloid protein (Aß) in ß-amyloid plaques (APs). On this basis, we investigated whether vascular endothelial growth factor (VEGF), a growth factor with important neuroprotective activity, may provide a therapeutic opportunity for treating AD. We initially found that the expression and production of VEGF was downregulated in the brains of Tg2576 mice during the course of AD development and progression. Restoring VEGF in the brains of Tg2576 mice antagonized the production and deposit of Aß in Tg2576 mice. The addition of VEGF concurrently increased the expression of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and decreased the expression of ß-site APP cleaving enzyme 1 (BACE1), which contributes to the enhanced clearance of Aß in vivo. By decreasing the production and deposit of Aß, VEGF improved the cognitive decline of Tg2576 mice. These observations provide a novel implication for VEGF as a therapeutic approach for the treatment of AD.

Corrigendum: Clinical Characteristics and Predictors of Outcome for Onconeural Antibody-Associated Disorders: A Retrospective Analysis.

[This corrects the article DOI: 10.3389/fneur.2017.00584.].

Clinical Characteristics and Predictors of Outcome for Onconeural Antibody-Associated Disorders: A Retrospective Analysis.

Objective: To describe and analyze the clinical characteristics, laboratory data, management, and outcome of patients with onconeural antibody-associated disorders (OAAD) and identify predictors for poor outcome. Methods: This was a retrospective review of all patients with potential OAAD, who were hospitalized in Jinan General Hospital between September 2009 and July 2017. We clarified the diagnosis, collected comprehensive information and categorized patients into three groups: paraneoplastic neurological disorders (PNDs), autoimmune encephalitis (AE), and possible OAAD. Within the three groups, we analyzed a range of clinical and laboratory parameters and used univariate and multivariate regression analysis to identify predictors for poor outcome [modified Rankin Scale (mRS) = 3-6]. Results: From 158 patients, we identified 70 who fulfilled the criteria for OAAD, including 44 men (62.9%) and 26 women (37.1%). There were 38 patients (54.3%) in the PNDs group, 14 patients (20%) in the AE group, and 18 patients (25.7%) in the possible OAAD group. After the last follow-up, 14 (36.8%), 9 (64.2%), and 12 (66.7%) had a good outcome (mRS = 0-2). However, 6 (15.8%), 2 (14.3%), and 3 (16.7%) died, respectively. Univariate analysis showed that duration prior to the hospital (p = 0.0224) and urinary incontinence/retention (p = 0.0043) were associated with poor outcome (mRS = 3-6). After multivariate regression analysis, urinary incontinence/retention (p = 0.0388) and an immunocompromised state (p = 0.0247) remained as significant factors for poor outcome. Conclusion: Urinary incontinence/retention and an immunocompromised state represent significant predictors of a worse prognosis for patients with OAAD. By contrast, the results showed that [corrected] cerebrospinal fluid analysis, serum autoantibodies and tumor markers, [corrected] the function of crucial organs, electrophysiology, and radiological findings were not associated with a poor outcome.

Endothelial Progenitor Cells for Ischemic Stroke: Update on Basic Research and Application.

Ischemic stroke is one of the leading causes of human death and disability worldwide. So far, ultra-early thrombolytic therapy is the most effective treatment. However, most patients still live with varying degrees of neurological dysfunction due to its narrow therapeutic time window. It has been confirmed in many studies that endothelial progenitor cells (EPCs), as a kind of adult stem cells, can protect the neurovascular unit by repairing the vascular endothelium and its secretory function, which contribute to the recovery of neurological function after an ischemic stroke. This paper reviews the basic researches and clinical trials of EPCs especially in the field of ischemic stroke and addresses the combination of EPC application with new technologies, including neurovascular intervention, synthetic particles, cytokines, and EPC modification, with the aim of shedding some light on the application of EPCs in treating ischemic stroke in the future.

Catechol degradation on hematite/silica-gas interface as affected by gas composition and the formation of environmentally persistent free radicals.

Environmentally persistent free radicals (EPFRs) formed on a solid particle surface have received increasing attention because of their toxic effects. However, organic chemical fate regulated by EPFRs has rarely been investigated, and this information may provide the missing link in understanding their environmental behavior. Previous studies have suggested that the reduction of transition metals is involved in EPFRs formation. We thus hypothesize that an oxidative environment may inhibit EPFRs formation in particle-gas interface, which will consequently release free radicals and accelerate organic chemical degradation. Our result indicates that a 1% hematite coating on a silica surface inhibited catechol degradation in N2, especially at low catechol loadings on solid particles (SCT). However, under an O2 environment, catechol degradation decreased when SCT was <1 µg/mg but increased when SCT was >1 µg/mg. Stable organic free radicals were observed in the N2 system with g factors in the 2.0035-2.0050 range, suggesting the dominance of oxygen-centered free radicals. The introduction of O2 into the catechol degradation system substantially decreased the free radical signals and decreased the Fe(II) content. These results were observed in both dark and light irradiation systems, indicating the ubiquitous presence of EPFRs in regulating the fate of organic chemicals.

Structural benefits of bisphenol S and its analogs resulting in their high sorption on carbon nanotubes and graphite.

Bisphenol S (BPS), a new bisphenol analog, is considered to be a potential replacement for bisphenol A (BPA), which has gained concern because of its potentially adverse health impacts. Therefore, studies are needed to investigate the environmental fate and risks of this compound. In this study, the adsorption of BPS and four structural analogs on multi-walled carbon nanotubes (MWCNTs) and graphite (GP) were investigated. When solid-phase concentrations were normalized by the surface areas, oxygen-containing functional groups on the absorbents showed a positive impact on phenol sorption but inhibited the sorption of chemicals with two benzene rings. Among BPS analogs, diphenyl sulfone showed the lowest sorption when hydrophobic effects were ruled out. Chemicals with a butterfly structure, formed between the two benzene rings, showed consistently high sorption on MWCNTs, independent of the substituted electron-donating or accepting functional groups. This study emphasizes the importance of chemical conformation on organic, contaminant sorption on engineered, carbonaceous materials.

Quantifying the dynamic fluorescence quenching of phenanthrene and ofloxacin by dissolved humic acids.

Fluorescence quenching includes dynamic and static quenching, and both processes can alter the behavior and reactivity of the fluorescer. However, dynamic quenching is seldom quantified. This study combined dialysis equilibrium and fluorescence quenching methods to compare the contribution of dynamic and static quenching. The results indicate that phenanthrene (PHE)-DHA binding increased with DHA hydrophobicity, while ofloxacin (OFL)-DHA interaction showed the opposite effect. For PHE,the contribution of dynamic quenching to the overall fluorescence quenching was in the range of 50%~82% and decreased to 11%~58% with increased DHA hydrophobicity. However, OFL dynamic quenching increased from 2%~27% to 31%~61% with DHA hydrophobicity. Combining the results using model chemicals, we concluded that the carboxyl groups in DHA might be the primary components for PHE dynamic quenching and might be responsible for both dynamic and static quenching of OFL. Extensive study is needed to explore the quantitative relationship of dynamic quenching and chemical/DHA properties.

Organic matter source and degradation as revealed by molecular biomarkers in agricultural soils of Yuanyang terrace.

Three soils with different tillage activities were collected and compared for their organic matter sources and degradation. Two soils (TD and TP) with human activities showed more diverse of chemicals in both free lipids and CuO oxidation products than the one (NS) without human activities. Branched alkanoic acids only accounted for less than 5% of lipids, indicating limited microbial inputs in all three investigated soils. The degradation of lignin in NS and TD was relatively higher than TP, probably because of the chemical degradation, most likely UV light-involved photodegradation. Lignin parameters obtained from CuO oxidation products confirmed that woody gymnosperm tissue (such as pine trees) may be the main source for NS, while angiosperm tissues from vascular plant may be the predominant source for the lignins in TD and TP. Analysis of BPCAs illustrated that BC in NS may be mainly originated from soot or other fossil carbon sources, whereas BC in TD and TP may be produced during corn stalk and straw burning. BC was involved in mineral interactions for TD and TP. The dynamics of organic matter needs to be extensively examined for their nonideal interactions with contaminants.

Formation of environmentally persistent free radicals as the mechanism for reduced catechol degradation on hematite-silica surface under UV irradiation.

Iron is rich in soils, and is recently reported to form stable complexes with organic free radicals, generating environmentally persistent free radicals (EPFRs). The observation may challenge the common viewpoint that iron is an effective catalyst to facilitate the degradation of various organic chemicals. But no study was specifically designed to investigate the possible inhibited degradation of organic chemicals because of the formation of EPFRs in dry environment. We observed that catechol degradation under UV irradiation was decreased over 20% in silica particles coated with 1% hematite in comparison to uncoated silica particles. Stabilized semiquinone or quinine and phenol radicals were involved in HMT-silica system. EPFR formation was thus the reason for the reduced catechol degradation on HMT-silica surface under UV irradiation at ambient temperature. EPFRs should be incorporated in the studies of organic contaminants geochemical behavior, and will be a new input in their environmental fate modeling.

The sorption of heavy metals on thermally treated sediments with high organic matter content.

A sediment sample with organic matter higher than 60% was thermally treated and the sorption of Cu(II), Cd(II), and Pb(II) was investigated and compared to evaluate the potential use of sediments with high organic matter content to produce biochar. Cu(II) and Cd(II) sorption generally decreased with increasing pyrolysis temperature, concurred with decreased oxygen-containing functional groups of the adsorbents. Sediment particles pyrolyzed at 400 and 500 °C showed higher sorption to Pb(II) than other temperatures. The small hydrated ionic radius of Pb(II) may enable its close contact with solid particles and thus facilitated the diffusion of Pb(II) into the pores and the formation of cation-π bond with aromatic structures generated by pyrolysis. The sorption of heavy metals in thermally treated sediment showed comparable sorption to or higher sorption than natural adsorbents and biochars from biomass, suggesting their possible significant impact on the transport and risk of heavy metals.

Co-sorption of ofloxacin and Cu(II) in soils before and after organic matter removal.

Various mechanisms play roles simultaneously for antibiotic sorption on solid particles. Previous studies simply emphasized mechanisms that match the increased or decreased antibiotic sorption by metal ions, without a general concept including these diverse mechanisms in their co-sorption. We observed both increased and decreased OFL and Cu(II) sorption in their co-sorption system. The comparison of the sorption coefficients of primary adsorbate (Kd(pri)) and co-adsorbate (Kd(co)) suggested that enhanced sorption occurred at high Kd(pri) region (low primary adsorbate concentration). Competitive sorption was observed when Kd(pri) was decreased to a certain value depending on solid particle properties. We thus summarized that if the adsorbates were introduced with low concentrations, OFL (such as hydrophobic region in solid particles) and Cu(II) (such as inner-sphere complexation sites) occupied their unique high-energy sorption sites. Cu(II) complexed with the adsorbed OFL, and OFL bridged by the adsorbed Cu(II) promoted the sorption for both chemicals. With the increased concentrations, the adsorbates spread to some common sorption sites with low sorption energy, such as cation exchange and electrostatic attraction region. The overlapping of Cu(II) and OFL on these sorption sites resulted in competitive sorption at high concentrations. The previously reported apparently increased or decreased sorption in antibiotic-metal ion co-sorption system may be only a part of the whole picture. Extended study on the turning point of decreased and increased sorption relating to water chemistry conditions and solid particle properties will provide more useful information to predict antibiotic-metal ion co-sorption.

Sorption affinities of sulfamethoxazole and carbamazepine to two sorbents under co-sorption systems.

The Kd of sulfamethoxazole (SMX) on activated carbon (AC) was larger than that of SMX on single-walled carbon nanotubes (SC), but the competition of SMX with carbamazepine (CBZ) for adsorption sites was weaker on AC than SC. Thus, a large Kd value does not necessarily reflect a high affinity. The analysis of the apparent sorption, competition, desorption hysteresis, and the sorption thermodynamics for SMX and CBZ did not provide sufficient information to distinguish their sorption affinities. The release of the adsorbed CBZ was not altered with SMX as the competitor, but SMX release increased significantly after CBZ addition. The higher sorption affinity of CBZ may be explained by the interactions of the CBZ benzene rings with the aromatic structures of the adsorbents. Although the thermodynamic meaning cannot be described, the release ratio of the adsorbed pollutants provides useful information for understanding pollutant sorption strength and associated risks.