Patehealy0170

85±0.33 μV (P=.005); C-SKNA from 1.36±0.67 μV to 1.05±0.49 μV (P=.11). The frequency of L-burst episodes (2.87±1.61 n/min vs 1.13±0.99 n/min, P less then .001), mean L-SKNA during burst (1.82±0.79 μV vs 1.15±0.44 μV, P less then .001), and nonburst periods (1.09±0.60 μV vs 0.75±0.32 μV, P=.03) significantly decreased after LCSD, while the frequency of C-burst episodes (P=.57), mean C-SKNA during burst (P=.44), and nonburst periods (P=.10) did not change significantly. No arrhythmic events were documented after 11.9 months (range, 3.0-22.2 months) of follow-up. CONCLUSION LCSD provides an inhibitory effect on cardiac sympathetic activity by suppressing burst discharge as measured by SKNA. INTRODUCTION Host cell proteins (HCPs) are contaminated proteins remaining after purification of biopharmaceuticals. Recent reports revealed clinical implications of HCPs in anti-drug antibody (ADA) development in patients without any inflammatory effects. Therefore, we evaluated the inflammatory effects and immunogenicity of HCPs in an in vivo study by intravitreal administration to rabbits and an in vitro THP-1 cells assay. METHODS Escherichia coli-derived HCPs at 200 ng/eye with or without ranibizumab at 0.25 mg/eye were administrated intravitreally to rabbits. For in vitro examination, differentiated THP-1 cells were stimulated with HCPs at 0.17 to 10.88 μg/mL with or without ranibizumab at 0.2 mg/mL. RESULTS Co-administration of HCPs with ranibizumab, but not HCPs alone, induced ocular inflammation. Presence of ADA (anti-ranibizumab) was detected in the vitreous fluid of rabbits in which HCPs and ranibizumab were co-administered. HCPs increased cytokine release and upregulated cell surface markers involved in the antigen presentation in the THP-1 cell assay, which was enhanced by co-stimulation with ranibizumab. DISCUSSION These finding suggests that HCPs may induce inflammation and immunogenicity as an adjuvant. Furthermore, integrated analyses by an in vivo rabbit model and in vitro assay system using THP-1 cells would be useful to evaluate the immunological risk of HCPs. INTRODUCTION Development of agonistic analgesic drugs requires proof of selectivity in vivo attainable by selective antagonists or several knockdown strategies. The Kv7.2 potassium channel encoded by the KCNQ2 gene regulates neuronal excitability and its activation inhibits nociceptive transmission. Although it is a potentially attractive target for analgesics, no clinically approved Kv7.2 agonists are currently available and selectivity of drug candidates is hard to demonstrate in vivo due to the expenditure to generate KCNQ2 knockout animals and the lack of Kv7.2 selective antagonists. The present study describes the set-up of an RNA interference-based model that allows studying the selectivity of Kv7.2 openers. METHODS Adeno-associated virus (AAV) vectors were used to deliver the expression cassette for a short hairpin RNA targeting KCNQ2. Heat nociception was tested in rats after intrathecal AAV treatment. RESULTS Surprisingly, screening of AAV serotypes revealed serotype 7, which has rarely been explored, to be best suited for transduction of dorsal root ganglia neurons following intrathecal injection. Knockdown of the target gene was confirmed by qRT-PCR and the anti-nociceptive effect of a Kv7.2 agonist was found to be completely abolished by the treatment. DISCUSSION We consider this approach not only to be suitable to study the selectivity of novel analgesic drugs targeting Kv7.2, but rather to serve as a general fast and simple method to generate functional and phenotypic knockdown animals during drug discovery for central and peripheral pain targets. The aerobic denitrification process is a promising and cost-effective alternative to the conventional nitrogen removal process. Widely used ZnO nanoparticles (NPs) will inevitably reach wastewater treatment plants, and cause adverse impacts on aerobic denitrification and nitrogen removal. Therefore, a full understanding of the responses and adaption of aerobic denitrifiers to ZnO NPs is essential to develop effective strategies to reduce adverse effects on wastewater treatment. In this study, the responses and adaption to ZnO NPs were investigated of a wild type strain (WT) and a resistant type strain (Re) of aerobic denitrifying bacteria Enterobacter cloacae strain HNR. When exposed to 0.75 mM ZnO NPs, the nitrate removal efficiency of Re was 11.2% higher than that of WT. To prevent ZnO NPs entering cells by adsorption, the production of extracellular polymeric substances (EPS) of WT and Re strains increased 13.2% and 43.9%, respectively. The upregulations of amino sugar and carbohydrate-related metabolism contributed to the increase of EPS production, and the increased nitrogen metabolism contributed to higher activities of nitrate and nitrite reductases. Interestingly, cationic antimicrobial peptide resistance contributed to resist Zn (II) released by ZnO NPs, and many antioxidative stress-related metabolism pathways were upregulated to resist the oxidative stress resulting from ZnO NPs. These findings will guide efforts to improve the aerobic denitrification process in an environment polluted by NPs, and promote the application of aerobic denitrification technologies. BACKGROUND Influenza viruses evolve rapidly and cause regular seasonal epidemics in humans challenging effective vaccination. The virus surface HA glycoprotein is the primary target for the host immune response. Here, we investigated the vaccine efficacy and evolution patterns of human influenza A/H3N2 viruses that circulated in Kenyan in the period before and after the 2009 A/H1N1 pandemic, targeting the HA1 domain. MATERIALS AND METHODS A hundred and fifteen HA sequences of Kenyan virus viruses were analyzed relative to the corresponding WHO vaccine reference strains using bioinformatics approaches. RESULTS Our analyses revealed varied amino acid substitutions at all the five antigenic sites (A-E) of the HA1 domain, with a majority the changes occurring at sites A and B. The Kenyan A/H3N2 viruses isolated during 2007/2008 seasons belonged to A/Brisbane/10/2007- like viruses lineage, while those circulating in 2009 to 2012 belonged to the lineage of A/Victoria/361/2011-like viruses. SD49-7 The 2013 viruses clustered in clade 3C.