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https://www.readbyqxmd.com/read/29748655/normalizing-resting-energy-expenditure-across-the-life-course-in-humans-challenges-and-hopes
#1
REVIEW
Manfred J Müller, Corinna Geisler, Mark Hübers, Maryam Pourhassan, Wiebke Braun, Anja Bosy-Westphal
Whole-body daily energy expenditure is primarily due to resting energy expenditure (REE). Since there is a high inter-individual variance in REE, a quantitative and predictive framework is needed to normalize the data. Complementing the assessment of REE with data normalization makes individuals of different sizes, age, and sex comparable. REE is closely correlated with body mass suggesting its near constancy for a given mass and, thus, a linearity of this association. Since body mass and its metabolic active components are the major determinants of REE, they have been implemented into allometric modeling to normalize REE for quantitative differences in body weight and/or body composition...
May 2018: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29739901/compositional-and-functional-differences-in-the-human-gut-microbiome-correlate-with-clinical-outcome-following-infection-with-wild-type-salmonella-enterica-serovar-typhi
#2
Yan Zhang, Arthur Brady, Cheron Jones, Yang Song, Thomas C Darton, Claire Jones, Christoph J Blohmke, Andrew J Pollard, Laurence S Magder, Alessio Fasano, Marcelo B Sztein, Claire M Fraser
Insights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut microbiota. In the present study, we characterized the composition (16S rRNA gene profiling) and function (RNA sequencing [RNA-seq]) of the gut microbiota following immunization and subsequent exposure to wild-type Salmonella enterica serovar Typhi in a human challenge model to further investigate the central hypothesis that clinical outcomes may be linked to the gut microbiota...
May 8, 2018: MBio
https://www.readbyqxmd.com/read/29726994/treatment-of-human-challenge-and-mdr-strains-of-neisseria-gonorrhoeae-with-lpxc-inhibitors
#3
Constance M John, Dongxiao Feng, Gary A Jarvis
Objectives: Inhibitors of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC), which catalyses the second step in the biosynthesis of lipid A, have been developed as potential antibiotics for Gram-negative infections. Our objectives were to determine the effect of LpxC inhibition on the in vitro survival and inflammatory potential of Neisseria gonorrhoeae. Methods: Survival of four human challenge strains was determined after treatment with two LpxC inhibitors for 2 and 4 h...
May 2, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29702652/impact-of-lower-challenge-doses-of-enterotoxigenic-escherichia-coli-on-clinical-outcome-intestinal-colonization-and-immune-responses-in-adult-volunteers
#4
Subhra Chakraborty, Clayton Harro, Barbara DeNearing, Jessica Brubaker, Sean Connor, Nicole Maier, Len Dally, Jorge Flores, A Louis Bourgeois, Richard Walker, David A Sack
A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60-70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used...
April 27, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29694356/impact-of-confinement-housing-on-study-end-points-in-the-calf-model-of-cryptosporidiosis
#5
Geneva Graef, Natalie J Hurst, Lance Kidder, Tracy L Sy, Laura B Goodman, Whitney D Preston, Samuel L M Arnold, Jennifer A Zambriski
BACKGROUND: Diarrhea is the second leading cause of death in children < 5 years globally and the parasite genus Cryptosporidium is a leading cause of that diarrhea. The global disease burden attributable to cryptosporidiosis is substantial and the only approved chemotherapeutic, nitazoxanide, has poor efficacy in HIV positive children. Chemotherapeutic development is dependent on the calf model of cryptosporidiosis, which is the best approximation of human disease. However, the model is not consistently applied across research studies...
April 25, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29686064/protection-from-cytomegalovirus-viremia-following-glycoprotein-b-vaccination-is-not-dependent-on-neutralizing-antibodies
#6
Ilona Baraniak, Barbara Kropff, Lyn Ambrose, Megan McIntosh, Gary R McLean, Sylvie Pichon, Claire Atkinson, Richard S B Milne, Michael Mach, Paul D Griffiths, Matthew B Reeves
Human cytomegalovirus (HCMV) is an important pathogen in transplant patients and in congenital infection. Previously, we demonstrated that vaccination with a recombinant viral glycoprotein B (gB)/MF59 adjuvant formulation before solid organ transplant reduced viral load parameters post transplant. Reduced posttransplant viremia was directly correlated with antibody titers against gB consistent with a humoral response against gB being important. Here we show that sera from the vaccinated seronegative patients displayed little evidence of a neutralizing antibody response against cell-free HCMV in vitro...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29590182/clinical-endpoints-in-the-controlled-human-challenge-model-for-shigella-a-call-for-standardization-and-the-development-of-a-disease-severity-score
#7
Chad K Porter, Amanda Lynen, Mark S Riddle, Kawsar Talaat, David Sack, Ramiro L Gutiérrez, Robin McKenzie, Barbara DeNearing, Brittany Feijoo, Robert W Kaminski, David N Taylor, Beth D Kirkpatrick, A Louis Bourgeois
BACKGROUND: Since 1946 the controlled human infection model (CHIM) for Shigella has been used to improve understanding of disease pathogenesis, describe clinical and immunologic responses to infection and as a tool for vaccine development. As the frequency and intent for use in vaccine comparisons increases, standardization of the primary endpoint definition is necessary. METHODS: Subject-level data were obtained from previously conducted experimental Shigella CHIM studies...
2018: PloS One
https://www.readbyqxmd.com/read/29577084/aggregative-adherence-and-intestinal-colonization-by-enteroaggregative-escherichia-coli-are-produced-by-interactions-among-multiple-surface-factors
#8
Laura V Blanton, Lawrence T Wang, Jennifer Hofmann, Joshua DuBow, Alexander Lafrance, Stephen Kwak, Levi Bowers, Mandara A Levine, Charles O Hale, Philip M Meneely, Iruka N Okeke
Enteroaggregative Escherichia coli (EAEC) bacteria are exceptional colonizers that are associated with diarrhea. The genome of EAEC strain 042, a diarrheal pathogen validated in a human challenge study, encodes multiple colonization factors. Notable among them are aggregative adherence fimbriae (AAF/II) and a secreted antiaggregation protein (Aap). Deletion of aap is known to increase adherence, autoaggregation, and biofilm formation, so it was proposed that Aap counteracts AAF/II-mediated interactions. We hypothesized that Aap sterically masks heat-resistant agglutinin 1 (Hra1), an integral outer membrane protein recently identified as an accessory colonization factor...
March 2018: MSphere
https://www.readbyqxmd.com/read/29573967/human-challenge-trials-in-vaccine-development-rockville-md-usa-september-28-30-2017
#9
Marc F D Baay, Thomas L Richie, Pieter Neels
The International Alliance for Biological Standardization organized the second workshop on human challenge trials (HCT) in Rockville, MD, in September 2017. The objective of this meeting was to examine the use of HCT, in response to the continuing human suffering caused by infectious diseases, preventable by the development of new and improved vaccines. For this, the approach of HCT could be valuable, as HCT can provide key safety, tolerability, immunogenicity, and efficacy data, and can be used to study host-pathogen biology...
March 21, 2018: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/29570776/the-roles-of-resident-central-and-effector-memory-cd4-t-cells-in-protective-immunity-following-infection-or-vaccination
#10
REVIEW
Joshua I Gray, Lotus M Westerhof, Megan K L MacLeod
Immunological memory provides rapid protection to pathogens previously encountered through infection or vaccination. CD4 T cells play a central role in all adaptive immune responses. Vaccines must, therefore, activate CD4 T cells if they are to generate protective immunity. For many diseases, we do not have effective vaccines. These include HIV, tuberculosis and malaria, which are responsible for many millions of deaths each year across the globe. CD4 T cells play many different roles during the immune response coordinating the actions of many other cells...
March 23, 2018: Immunology
https://www.readbyqxmd.com/read/29479558/plasma-menthol-glucuronide-as-a-biomarker-of-acute-menthol-inhalation
#11
Peter Jatlow, Gerald Valentine, Ralitza Gueorguieva, Haleh Nadim, Ran Wu, Stephanie S O'Malley, Mehmet Sofuoglu
Objectives: Menthol is often added to cigarettes and e-cigarette solutions for its cooling and anti-irritant effects, and may contribute to development of nicotine dependence, particularly in vulnerable populations such as adolescents, and among African Americans. Menthol is rapidly metabolized to menthol glucuronide (MG) with little or no unconjugated menthol measurable in venous blood. Human challenge studies of the effects of inhaled menthol, and of its interactions with nicotine, would benefit from a quantitative measure of acute menthol exposure...
January 2018: Tobacco Regulatory Science
https://www.readbyqxmd.com/read/29382797/novel-anti-tumour-necrosis-factor-receptor-1-tnfr1-domain-antibody-prevents-pulmonary-inflammation-in-experimental-acute-lung-injury
#12
Alastair Proudfoot, Andrew Bayliffe, Cecilia M O'Kane, Tracey Wright, Adrian Serone, Philippe Jean Bareille, Vanessa Brown, Umar I Hamid, Younan Chen, Robert Wilson, Joanna Cordy, Peter Morley, Ruud de Wildt, Stuart Elborn, Matthew Hind, Edwin R Chilvers, Mark Griffiths, Charlotte Summers, Daniel Francis McAuley
BACKGROUND: Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 and TNFR2. In the setting of acute injury, selective inhibition of TNFR1 is predicted to attenuate the cell death and inflammation associated with TNF-α, while sparing or potentiating the protective effects of TNFR2 signalling. We developed a potent and selective antagonist of TNFR1 (GSK1995057) using a novel domain antibody (dAb) therapeutic and assessed its efficacy in vitro, in vivo and in a clinical trial involving healthy human subjects...
January 29, 2018: Thorax
https://www.readbyqxmd.com/read/29362240/evaluation-of-preexisting-anti-hemagglutinin-stalk-antibody-as-a-correlate-of-protection-in-a-healthy-volunteer-challenge-with-influenza-a-h1n1pdm-virus
#13
Jae-Keun Park, Alison Han, Lindsay Czajkowski, Susan Reed, Rani Athota, Tyler Bristol, Luz Angela Rosas, Adriana Cervantes-Medina, Jeffery K Taubenberger, Matthew J Memoli
Influenza virus hemagglutinin (HA) surface glycoprotein is currently the primary target of licensed influenza vaccines. Recently, broadly reactive antibodies that target the stalk region of the HA have become a major focus of current novel vaccine development. These antibodies have been observed in humans after natural infection with influenza A virus, but the data are limited. Using samples and data from the uniquely controlled setting of an influenza A/H1N1 virus human challenge study of healthy volunteers, we performed a secondary analysis that for the first time explores the role of anti-HA stalk antibody as a human correlate of protection...
January 23, 2018: MBio
https://www.readbyqxmd.com/read/29324233/bcg-vaccination-protects-against-experimental-viral-infection-in-humans-through-the-induction-of-cytokines-associated-with-trained-immunity
#14
Rob J W Arts, Simone J C F M Moorlag, Boris Novakovic, Yang Li, Shuang-Yin Wang, Marije Oosting, Vinod Kumar, Ramnik J Xavier, Cisca Wijmenga, Leo A B Joosten, Chantal B E M Reusken, Christine S Benn, Peter Aaby, Marion P Koopmans, Hendrik G Stunnenberg, Reinout van Crevel, Mihai G Netea
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity...
January 10, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29286657/the-transferability-from-animal-models-to-humans-challenges-regarding-aggregation-and-protein-corona-formation-of-nanoparticles
#15
Laura K Müller, Johanna Simon, Christine Rosenauer, Volker Mailänder, Svenja Morsbach, Katharina Landfester
Nanomaterials are interesting candidates for applications in medicine as drug delivery or diagnostic agents. For safe application, they have to be evaluated in in vitro and in vivo models to finally be translated to human clinical trials. However, often those transfer processes fail, and it is not completely understood whether in vitro models leading to these animal models can reliably be compared to the situation in humans. In particular, the interaction of nanomaterials with components from different blood plasma sources is difficult to compare, and the outcomes of those interactions with respect to body distribution and cell uptake are unclear...
February 12, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29251602/controlled-human-infection-models-for-vaccine-development-zika-virus-debate
#16
Vijayaprasad Gopichandran
An ethics panel, convened by the National Institute of Health and other research bodies in the USA, disallowed researchers from the Johns Hopkins University and University of Vermont from performing controlled human infection of healthy volunteers to develop a vaccine against Zika virus infection. The members published their ethical analysis and recommendations in February 2017. They have elaborated on the risks posed by human challenge with Zika virus to the volunteers and other uninvolved third parties and have systematically analysed the social value of such a human challenge experiment...
January 2018: Indian Journal of Medical Ethics
https://www.readbyqxmd.com/read/29167342/antibodies-directed-toward-neuraminidase-n1-control-disease-in-a-mouse-model-of-influenza
#17
E R Job, M Schotsaert, L I Ibañez, A Smet, T Ysenbaert, K Roose, M Dai, C A M de Haan, H Kleanthous, T U Vogel, X Saelens
There is increasing evidence to suggest that antibodies directed toward influenza A virus (IAV) neuraminidase (NA) are an important correlate of protection against influenza in humans. Moreover, the potential of NA-specific antibodies to provide broader protection than conventional hemagglutinin (HA) antibodies has been recognized. Here, we describe the isolation of two monoclonal antibodies, N1-7D3 and N1-C4, directed toward the N1 NA. N1-7D3 binds to a conserved linear epitope in the membrane-distal, carboxy-terminal part of the NA and reacted with the NA of seasonal H1N1 isolates ranging from 1977 to 2007 and the 2009 H1N1pdm virus, as well as A/Vietnam/1194/04 (H5N1)...
February 15, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29145631/rifaximin-fails-to-prevent-campylobacteriosis-in-the-human-challenge-model-a-randomized-double-blind-placebo-controlled-trial
#18
Joanna E Rimmer, Clayton Harro, David A Sack, Kawsar R Talaat, Ramiro L Gutierrez, Barbara DeNearing, Jessica Brubaker, Renee M Laird, Frédéric Poly, Alexander C Maue, Kayla Jaep, Ashley Alcala, Yelizaveta Mochalova, Christina L Gariepy, Subhra Chakraborty, Patricia Guerry, David R Tribble, Chad K Porter, Mark S Riddle
Background: Campylobacter species are a leading cause of diarrheal disease globally with significant morbidity. Primary prevention efforts have yielded limited results. Rifaximin chemoprophylaxis decreases rates of travelers' diarrhea and may be suitable for high-risk persons. We assessed the efficacy of rifaximin in the controlled human infection model for Campylobacter jejuni. Methods: Twenty-eight subjects were admitted to an inpatient facility and randomized to a twice-daily dose of 550 mg rifaximin or placebo...
April 17, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29095059/tendon-transfer-surgery-focus-on%C3%A2
#19
Roberto Cuomo, Luca Grimaldi, Giuseppe Nisi, Cesare Brandi, Carlo D'Aniello
Median and Ulnar nerve palsy is a devastating condition that compromise hand function. A procedure of tendon transfer may be helpful to restore the movements by linking palsy muscles to other muscles able to contract. Scientific discoveries and technological innovations have profoundly changed this kind of surgery; studies on sarcomeres, for example, changed the concept of tensioning. To date we know that muscle strength and its contraction capacity depends on many factors (not only tensioning) such as sarcomeres length, cellular cytoskeleton and extracellular matrix composition: all of these factors interact together and in a ways not still fully understood, determining the complex concept of "movement...
November 2, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/29025851/investigating-bordetella-pertussis-colonisation-and-immunity-protocol-for-an-inpatient-controlled-human-infection-model
#20
Hans de Graaf, Diane Gbesemete, Andrew R Gorringe, Dimitri A Diavatopoulos, Kent E Kester, Saul N Faust, Robert C Read
INTRODUCTION: We summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. Globally Bordetella pertussis is one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage. The acellular vaccine provides relatively short-lived immunity and, in contrast to whole cell vaccines, may be less effective against colonisation and subsequent transmission...
October 11, 2017: BMJ Open
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