A Tunable Band Stop Filter for Ku Band Communication Systems Using DGS and MEMS Switches

This paper presents a tunable bandstop filter based on an interdigital defected ground structure (DGS) and microelectromechanical (MEMS) switches. The switches are positioned over the bends of the DGS. Depending the switch that is actuated, the effective slot length of the DGS varies and hence the resonant frequency. The resonant frequencies can be further varied by varying the individual branch lengths. The proposed design is modified with three additional MEMS switches in each branch to alter its effective length. The design procedure for varying the branch lengths, and mechanical design of the MEMS switches is also presented. The additional switches create a large number of switching states filling the entire Ku- band with closely spaced resonant frequencies

Complete mitochondrial genome profile of Randall’s threadfin bream, Nemipterus randalli and its phylogenetic analysis

We characterized the complete mitogenome of Nemipterus randalli and performed comparative mitogenomic analysis with previously determined mitochondrial genomes belonging to the family Nemipteridae. Using Sanger sequencing, we identified a 16,642 bp mitogenome containing 37 genes (13 protein-coding, 2 rRNA, 22 tRNA) and a non-coding region. Its gene organization, nucleotide composition, tRNA secondary structure and codon usage are similar to other Nemipteridae mitogenomes. The phylogenetic analysis indicated that Nemipteridae is a monophyletic group. The present study forms the basis for further studies on the population genetics, evolution and phylogeny of N. randalli and its family

In vitro Characterization of Gut Microbiota-Derived Bacterial Strains With Neuroprotective Properties

Acknowledgments The authors are grateful to Dr. Nicole Reichardt and the 4D Pharma Isolation Team for their technical assistance with bacterial culture. Funding This work was privately funded by 4D Pharma PLC. The authors of the study, who are employees of (or in the case of MID, are funded by) 4D Pharma Research Ltd., a wholly owned subsidiary of the funder, were responsible for the design and execution of the study, as well as the analysis of the results obtained. Author Contributions In vitro experiments: AE, SA, and AB designed the experiments; SA, PF, NV, MG, SB, GB-A, and MD performed the majority of the in vitro experiments; SR, HD, and AB validated, performed, and analyzed the microbiological-related data output; AE coordinated and managed the research project; AE, SA, PF, and AB analyzed the data. IM oversaw the overall research plan. AE wrote the manuscript with the assistance of SA and AB. All authors have read and commented on the manuscript and have approved the final version of the manuscript. Data Availability: 16S gene sequences for MRx0005 and MRx0029 are disclosed in International Patent Publication Nos. WO2018/229189 and WO2018/229216, respectively, filed by 4D Pharma Research Ltd. The data supporting the findings in this paper are available within the article and its Supplementary Information Files.Peer reviewedPublisher PD

Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease

Chagas disease is the most common cause of congestive heart failure related deaths among young adults in the endemic areas of South and Central America and Mexico. Diagnosis and treatment of T. cruzi infection has remained difficult and challenging after 100 years of its identification. In >95% of human cases, T. cruzi infection remains undiagnosed until several years later when chronic evolution of progressive disease results in clinical symptoms associated with cardiac damage. Diagnosis generally depends on the measurement of T. cruzi'specific antibodies that can result in false positives. A conclusive diagnosis of T. cruzi infection thus often requires multiple serological tests, in combination with epidemiological data and clinical symptoms. In this study, we investigated the antibody response to TcG1, TcG2, and TcG4 in clinically characterized chagasic patients. These antigens were identified as vaccine candidates and shown to elicit protective immunity to T. cruzi and Chagas disease in experimental animals. Our data show the serology test developed using the TcGmix (multiplex ELISA) is a significantly better alternative to epimastigote extracts currently used in T. cruzi serodiagnosis or the trypomastigote lysate used in this study for comparison purposes.Fil: Gupta, Shivali. University Of Texas Medical Branch. Department Of Pathology; Estados UnidosFil: Wan, Xianxu. University Of Texas Medical Branch. Department Of Pathology; Estados UnidosFil: Zago, María Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Salta. Instituto de Patología Experimental; ArgentinaFil: Martinez Sellers, Valena C.. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Silva, Trevor S.. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Assiah, Dadjah. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Dhiman, Monisha. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Nuñez, Sonia. Provincia de Salta. Hospital Público de Gestion Descentralizada San Bernardo; ArgentinaFil: Petersen, John R.. University Of Texas Medical Branch. Department of Pathology; Estados UnidosFil: Vazquez Chagoyán, Juan C.. Universidad Autónoma de Estado de México ; MéxicoFil: Estrada Franco, Jose G.. Universidad Autónoma de Estado de México; MéxicoFil: Garg, Nisha Jain. University Of Texas Medical Branch. Department of Pathology; Estados Unido

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules

Background: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.<p></p> Methods: An in vitro multi-species biofilm containing <i>S. mitis, F. nucleatum, P. Gingivalis</i> and <i>A. Actinomycetemcomitans</i> was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.<p></p> Results: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.<p></p> Conclusions: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.<p></p&gt

Immune protection against Trypanosoma cruzi induced by TcVac4 in a canine model

Chagas disease, caused by Trypanosoma cruzi, is endemic in southern parts of the American continent. Herein, we have tested the protective efficacy of a DNA-prime/T. rangeli-boost (TcVac4) vaccine in a dog (Canis familiaris) model. Dogs were immunized with two-doses of DNA vaccine (pcDNA3.1 encoding TcG1, TcG2, and TcG4 antigens plus IL-12- and GMCSF- encoding plasmids) followed by two doses of glutaraldehyde-inactivated T. rangeli epimastigotes (TrIE); and challenged with highly pathogenic T. cruzi (SylvioX10/4) isolate. Dogs given TrIE or empty pcDNA3.1 were used as controls. We monitored post-vaccination and post-challenge infection antibody response by an ELISA, parasitemia by blood analysis and xenodiagnosis, and heart function by electrocardiography. Post-mortem anatomic and pathologic evaluation of the heart was conducted. TcVac4 induced a strong IgG response (IgG2>IgG1) that was significantly expanded post-infection, and moved to a nearly balanced IgG2/IgG1 response in chronic phase. In comparison, dogs given TrIE or empty plasmid DNA only developed high IgG titers with IgG2 predominance in response to T. cruzi infection. Blood parasitemia, tissue parasite foci, parasite transmission to triatomines, electrocardiographic abnormalities were significantly lower in TcVac4-vaccinated dogs than was observed in dogs given TrIE or empty plasmid DNA only. Macroscopic and microscopic alterations, the hallmarks of chronic Chagas disease, were significantly decreased in the myocardium of TcVac4-vaccinated dogs.We conclude that TcVac4 induced immunity was beneficial in providing resistance to T. cruzi infection, evidenced by control of chronic pathology of the heart and preservation of cardiac function in dogs. Additionally, TcVac4 vaccination decreased the transmission of parasites from vaccinated/infected animals to triatomines.CONACYT PROY No. 156701 UAEM PROY No. 2381/2006U National Institutes of Health/National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/Pages/ default.aspx GRANT NUMBER (AI072538) NJG; American Heart Association http://www.heart.org/ HEARTORG/ GRANT NUMBER (0855059F) to NJG

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen