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https://www.readbyqxmd.com/read/29145631/rifaximin-fails-to-prevent-campylobacteriosis-in-the-human-challenge-model-a-randomized-double-blind-placebo-controlled-trial
#1
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 travelers' diarrhea rates and may be suitable for high risk persons. We assessed the efficacy of rifaximin in the controlled human infection model (CHIM) 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...
November 14, 2017: 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
#2
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
#3
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
https://www.readbyqxmd.com/read/28987728/environmental-chemicals-and-breast-cancer-an-updated-review-of-epidemiological-literature-informed-by-biological-mechanisms
#4
REVIEW
Kathryn M Rodgers, Julia O Udesky, Ruthann A Rudel, Julia Green Brody
BACKGROUND: Many common environmental chemicals are mammary gland carcinogens in animal studies, activate relevant hormonal pathways, or enhance mammary gland susceptibility to carcinogenesis. Breast cancer's long latency and multifactorial etiology make evaluation of these chemicals in humans challenging. OBJECTIVE: For chemicals previously identified as mammary gland toxicants, we evaluated epidemiologic studies published since our 2007 review. We assessed whether study designs captured relevant exposures and disease features suggested by toxicological and biological evidence of genotoxicity, endocrine disruption, tumor promotion, or disruption of mammary gland development...
October 6, 2017: Environmental Research
https://www.readbyqxmd.com/read/28965714/typhoid-vaccine-development-with-a-human-challenge-model
#5
Nicholas A Feasey, Myron M Levine
No abstract text is available yet for this article.
September 28, 2017: Lancet
https://www.readbyqxmd.com/read/28820709/performance-of-a-high-sensitivity-rapid-diagnostic-test-for-plasmodium-falciparum-malaria-in-asymptomatic-individuals-from-uganda-and-myanmar-and-naive-human-challenge-infections
#6
Smita Das, Ihn Kyung Jang, Becky Barney, Roger Peck, John C Rek, Emmanuel Arinaitwe, Harriet Adrama, Maxwell Murphy, Mallika Imwong, Clare L Ling, Stephane Proux, Warat Haohankhunnatham, Melissa Rist, Annette M Seilie, Amelia Hanron, Glenda Daza, Ming Chang, Tomoka Nakamura, Michael Kalnoky, Paul Labarre, Sean C Murphy, James S McCarthy, Francois Nosten, Bryan Greenhouse, Sophie Allauzen, Gonzalo J Domingo
Sensitive field-deployable diagnostic tests can assist malaria programs in achieving elimination. The performance of a new Alere™ Malaria Ag P.f Ultra Sensitive rapid diagnostic test (uRDT) was compared with the currently available SD Bioline Malaria Ag P.f RDT in blood specimens from asymptomatic individuals in Nagongera, Uganda, and in a Karen Village, Myanmar, representative of high- and low-transmission areas, respectively, as well as in pretreatment specimens from study participants from four Plasmodium falciparum-induced blood-stage malaria (IBSM) studies...
August 7, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28798761/harnessing-finger-millet-to-combat-calcium-deficiency-in-humans-challenges-and-prospects
#7
REVIEW
Swati Puranik, Jason Kam, Pranav P Sahu, Rama Yadav, Rakesh K Srivastava, Henry Ojulong, Rattan Yadav
Humans require more than 20 mineral elements for healthy body function. Calcium (Ca), one of the essential macromineral, is required in relatively large quantities in the diet for maintaining a sound overall health. Young children, pregnant and nursing women in marginalized and poorest regions of the world, are at highest risk of Ca malnutrition. Elderly population is another group of people most commonly affected by Ca deficiency mainly in the form of osteoporosis and osteopenia. Improved dietary intake of Ca may be the most cost-effective way to meet such deficiencies...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28611093/danirixin-a-reversible-and-selective-antagonist-of-the-cxc-chemokine-receptor-2
#8
Jakob Busch-Petersen, Donald C Carpenter, Miriam Burman, James Foley, Gerald E Hunsberger, David J Kilian, Michael Salmon, Ruth J Mayer, John G Yonchuk, Ruth Tal-Singer
CXC chemokine receptor 2 (CXCR2) is a key receptor in the chemotaxis of neutrophils to sites of inflammation. The studies reported here describe the pharmacological characterization of danirixin, a CXCR2 antagonist in the diaryl urea chemical class. Danirixin has high affinity for CXCR2, with a negative log of the 50% inhibitory concentration (pIC50) of 7.9 for binding to Chinese hamster ovary cell (CHO)-expressed human CXCR2, and 78-fold selectivity over binding to CHO-expressed CXCR1. Danirixin is a competitive antagonist against CXCL8 in Ca(2+)-mobilization assays, with a KB (the concentration of antagonist that binds 50% of the receptor population) of 6...
August 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28610781/pilot-studies-of-a-human-bcg-challenge-model
#9
Azra Blazevic, Mei Xia, Aldin Turan, Janice Tennant, Daniel F Hoft
Despite the great effort to develop an effective vaccine against tuberculosis (TB) there is currently no reliable and safe human challenge model that can be used for in vivo evaluation of new TB vaccine candidates and/or elucidation of the mechanisms of TB protective immunity. In this study, five volunteers were challenged with BCG intradermally (ID). Swab specimens were collected at multiple time points from the vaccination site pre- and post-vaccination to quantitate mycobacterial shedding as a surrogate of in vivo mycobacterial immunity...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28606804/a-human-challenge-model-for-respiratory-syncytial-virus-kinetics-the-pharmacological-effect-of-a-novel-fusion-inhibitor-and-the-modelling-of%C3%A2-symptoms-scores
#10
Julia Korell, Bruce Green, John DeVincenzo, Dymphy Huntjens
Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections, and is a major cause of hospital admissions and death in young children. Limited treatments currently exist that can prevent or minimise exacerbation of the disease. The aims of this work were: 1) to develop a population pharmacodynamic model to describe RSV kinetics (RSVK) in nasal lavage, 2) evaluate the impact of an investigational fusion inhibitor, JNJ-53718678, on RSVK, and 3) determine the relationship between RSVK and symptoms scores...
November 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28583039/experimental-models-of-autoimmune-demyelinating-diseases-in-nonhuman-primates
#11
Lev Stimmer, Claire-Maëlle Fovet, Ché Serguera
Human idiopathic inflammatory demyelinating diseases (IIDD) are a heterogeneous group of autoimmune inflammatory and demyelinating disorders of the central nervous system (CNS). These include multiple sclerosis (MS), the most common chronic IIDD, but also rarer disorders such as acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica (NMO). Great efforts have been made to understand the pathophysiology of MS, leading to the development of a few effective treatments. Nonetheless, IIDD still require a better understanding of the causes and underlying mechanisms to implement more effective therapies and diagnostic methods...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28303138/importance-of-salmonella-typhi-responsive-cd8-t-cell-immunity-in-a-human-typhoid-fever-challenge-model
#12
Stephanie Fresnay, Monica A McArthur, Laurence S Magder, Thomas C Darton, Claire Jones, Claire S Waddington, Christoph J Blohmke, Brian Angus, Myron M Levine, Andrew J Pollard, Marcelo B Sztein
Typhoid fever, caused by the human-restricted organism Salmonella enterica serovar Typhi (S. Typhi), constitutes a major global health problem. The development of improved attenuated vaccines is pressing, but delayed by the lack of appropriate preclinical models. Herein, we report that high levels of S. Typhi-responsive CD8+ T cells at baseline significantly correlate with an increased risk of disease in humans challenged with a high dose (~10(4) CFU) wild-type S. Typhi. Typhoid fever development was associated with higher multifunctional S...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28158395/evaluation-of-the-clinical-and-microbiological-response-to-salmonella-paratyphi-a-infection-in-the-first-paratyphoid-human-challenge-model
#13
Hazel C Dobinson, Malick M Gibani, Claire Jones, Helena B Thomaides-Brears, Merryn Voysey, Thomas C Darton, Claire S Waddington, Danielle Campbell, Iain Milligan, Liqing Zhou, Sonu Shrestha, Simon A Kerridge, Anna Peters, Zoe Stevens, Audino Podda, Laura B Martin, Flavia D'Alessio, Duy Pham Thanh, Buddha Basnyat, Stephen Baker, Brian Angus, Myron M Levine, Christoph J Blohmke, Andrew J Pollard
Background: To expedite the evaluation of vaccines against paratyphoid fever, we aimed to develop the first human challenge model of Salmonella enterica serovar Paratyphi A infection. Methods: Two groups of 20 participants underwent oral challenge with S. Paratyphi A following sodium bicarbonate pretreatment at 1 of 2 dose levels (group 1: 1-5 × 103 colony-forming units [CFU] and group 2: 0.5-1 × 103 CFU). Participants were monitored in an outpatient setting with daily clinical review and collection of blood and stool cultures...
April 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28148797/patterns-of-cellular-immunity-associated-with-experimental-infection-with-rden2%C3%AE-30-tonga-74-support-its-suitability-as-a-human-dengue-virus-challenge-strain
#14
COMPARATIVE STUDY
Alba Grifoni, Michael Angelo, John Sidney, Sinu Paul, Bjoern Peters, Aruna D de Silva, Elizabeth Phillips, Simon Mallal, Sean A Diehl, Jason Botten, Jonathan Boyson, Beth D Kirkpatrick, Stephen S Whitehead, Anna P Durbin, Alessandro Sette, Daniela Weiskopf
A deletion variant of the dengue virus (DENV) serotype 2 (DENV2) Tonga/74 strain lacking 30 nucleotides from its 3' untranslated region (rDEN2Δ30) has previously been established for use in a controlled human DENV challenge model. To evaluate if this model is appropriate for the derivation of correlates of protection for DENV vaccines on the basis of cellular immunity, we wanted to compare the cellular immune response to this challenge strain to the response induced by natural infection. To achieve this, we predicted HLA class I- and class II-restricted peptides from rDEN2Δ30 and used them in a gamma interferon enzyme-linked immunosorbent spot assay to interrogate CD8(+) and CD4(+) T cell responses in healthy volunteers infected with rDEN2Δ30...
April 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28049817/global-urban-signatures-of-phenotypic-change-in-animal-and-plant-populations
#15
Marina Alberti, Cristian Correa, John M Marzluff, Andrew P Hendry, Eric P Palkovacs, Kiyoko M Gotanda, Victoria M Hunt, Travis M Apgar, Yuyu Zhou
Humans challenge the phenotypic, genetic, and cultural makeup of species by affecting the fitness landscapes on which they evolve. Recent studies show that cities might play a major role in contemporary evolution by accelerating phenotypic changes in wildlife, including animals, plants, fungi, and other organisms. Many studies of ecoevolutionary change have focused on anthropogenic drivers, but none of these studies has specifically examined the role that urbanization plays in ecoevolution or explicitly examined its mechanisms...
August 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27927680/functional-and-antigen-specific-serum-antibody-levels-as-correlates-of-protection-against-shigellosis-in-a-controlled-human-challenge-study
#16
Avital A Shimanovich, Amanda D Buskirk, Shannon J Heine, William C Blackwelder, Rezwanul Wahid, Karen L Kotloff, Marcela F Pasetti
Shigella is an important cause of diarrheal disease in young children living in developing countries. No approved vaccines are available, and the development of vaccine candidates has been hindered by the lack of firm immunological correlates of protection, among other reasons. To address this gap in knowledge, we established quantitative assays to measure Shigella-specific serum bactericidal antibody (SBA) and opsonophagocytic killing antibody (OPKA) activities and investigated their potential association with protection against disease in humans...
February 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/27889256/controlled-human-infection-with-rsv-the-opportunities-of-experimental-challenge
#17
Maximillian S Habibi, Christopher Chiu
Despite the recent explosion in RSV vaccine development, there remain substantial hurdles to overcome before licensing of effective vaccines will allow widespread use, particularly in high-risk populations. Incomplete understanding of mechanisms and correlates of protection against RSV mean that, for the time being, successful RSV vaccines must directly demonstrate efficacy, which necessitates large and costly clinical trials in naturally infected patients. To mitigate the risks inherent in progressing to these late-stage trials, experimental human RSV infection studies have recently been re-established, representing the interface between pre-clinical models and observational studies of patients...
January 11, 2017: Vaccine
https://www.readbyqxmd.com/read/27829492/forward-medevac-during-serval-and-barkhane-operations-in-sahel-a-registry-study
#18
Cyril Carfantan, Yvain Goudard, Christophe Butin, Sandrine Duron-Martinaud, Jean-Philippe Even, Anthony Anselme, Erwan Dulaurent, Mélanie Géhant, Vicky Vitalis, Christian Bay, Jérôme Bancarel, Julien Bordes
INTRODUCTION: The French army has been deployed in Mali since January 2013 with the Serval Operation and since July 2014 in the Sahel-Saharan Strip (SSS) with the Barkhane Operation where the distances (up to 1100km) can be very long. French Military Medical Service deploys an inclusive chain from the point of injury (POI) to hospital in France. A patient evacuation coordination cell (PECC) has been deployed since February 2013 to organise forward medical evacuation (MEDEVAC) in the area between the POI and three forward surgical units...
January 2017: Injury
https://www.readbyqxmd.com/read/27708621/reassessment-of-the-enteropathogenicity-of-mesophilic-aeromonas-species
#19
Peter Teunis, Maria J Figueras
Cases of Aeromonas diarrhea have been described all over the world. The genus Aeromonas includes ca. 30 species, of which 10 have been isolated in association with gastroenteritis. The dominating species that account for ca. 96% of the identified strains are Aeromonas caviae, A. veronii, A. dhakensis, and A. hydrophila. However, the role of Aeromonas as a true enteropathogen has been questioned on the basis of the lack of outbreaks, the non-fulfillment of Koch's postulates and the low numbers of acute illnesses in the only existing human challenge study...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27707932/deep-sequencing-of-influenza-a-virus-from-a-human-challenge-study-reveals-a-selective-bottleneck-and-only-limited-intrahost-genetic-diversification
#20
Ashley Sobel Leonard, Micah T McClain, Gavin J D Smith, David E Wentworth, Rebecca A Halpin, Xudong Lin, Amy Ransier, Timothy B Stockwell, Suman R Das, Anthony S Gilbert, Robert Lambkin-Williams, Geoffrey S Ginsburg, Christopher W Woods, Katia Koelle
Knowledge of influenza virus evolution at the point of transmission and at the intrahost level remains limited, particularly for human hosts. Here, we analyze a unique viral data set of next-generation sequencing (NGS) samples generated from a human influenza challenge study wherein 17 healthy subjects were inoculated with cell- and egg-passaged virus. Nasal wash samples collected from 7 of these subjects were successfully deep sequenced. From these, we characterized changes in the subjects' viral populations during infection and identified differences between the virus in these samples and the viral stock used to inoculate the subjects...
December 15, 2016: Journal of Virology
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