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Lyndon da Cruz, Kate Fynes, Odysseas Georgiadis, Julie Kerby, Yvonne H Luo, Ahmad Ahmado, Amanda Vernon, Julie T Daniels, Britta Nommiste, Shazeen M Hasan, Sakina B Gooljar, Amanda-Jayne F Carr, Anthony Vugler, Conor M Ramsden, Magda Bictash, Mike Fenster, Juliette Steer, Tricia Harbinson, Anna Wilbrey, Adnan Tufail, Gang Feng, Mark Whitlock, Anthony G Robson, Graham E Holder, Mandeep S Sagoo, Peter T Loudon, Paul Whiting, Peter J Coffey
Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more...
March 19, 2018: Nature Biotechnology
R Walker, D Pociecha, J P Abberley, A Martinez-Felipe, D A Paterson, E Forsyth, G B Lawrence, P A Henderson, J M D Storey, E Gorecka, C T Imrie
The spontaneous formation of a chiral phase via molecular recognition in a system consisting of achiral components is reported. Specifically, the liquid crystalline behaviour of two molecular complexes assembled by hydrogen bonding between a stilbazole-based template and alkoxybenzoic acids has been characterised. The complexes exhibit the heliconical twist-bend nematic phase (NTB) over a broad temperature range despite the hydrogen-bond acceptor not being liquid crystalline and the donor exhibiting the conventional achiral nematic phase...
March 19, 2018: Chemical Communications: Chem Comm
Harrison C Brown, Philip M Zakas, Stephan N George, Ernest T Parker, H Trent Spencer, Christopher B Doering
Potency is a key optimization parameter for hemophilia A gene therapy product candidates. Optimization strategies include promoter engineering to increase transcription, codon optimization of mRNA to improve translation, and amino-acid substitution to promote secretion. Herein, we describe both rational and empirical design approaches to the development of a minimally sized, highly potent AAV-fVIII vector that incorporates three unique elements: a liver-directed 146-nt transcription regulatory module, a target-cell-specific codon optimization algorithm, and a high-expression bioengineered fVIII variant...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Kelly Lien, Alvin Chin, Anton Helman, Teresa M Chan
Introduction Podcasts and blog posts have gained popularity in Free Open Access Medical education (FOAM). Previous work suggests that podcasts may be useful for knowledge acquisition in undergraduate medical education. However, there remains a paucity of research comparing the two mediums. This study aims to investigate if there are differences in knowledge acquisition and usage conditions by medical students using podcasts and blog posts. Methods Medical students were randomized to either the podcast or blog post group...
January 15, 2018: Curēus
Olaf Prieske, Tom Krüger, Markus Aehle, Erik Bauer, Urs Granacher
Power training programs have proved to be effective in improving components of physical fitness such as speed. According to the concept of training specificity, it was postulated that exercises must attempt to closely mimic the demands of the respective activity. When transferring this idea to speed development, the purpose of the present study was to examine the effects of resisted sprint (RST) vs. traditional power training (TPT) on physical fitness in healthy young adults. Thirty-five healthy, physically active adults were randomly assigned to a RST ( n = 10, 23 ± 3 years), a TPT ( n = 9, 23 ± 3 years), or a passive control group ( n = 16, 23 ± 2 years)...
2018: Frontiers in Physiology
Babak Ebrahimi, Bryan T Jackson, Julie L Guseman, Colin M Przybylowicz, Christopher M Stone, Woodbridge A Foster
Knowledge of the link between a vector population's pathogen-transmission potential and its biotic environment can generate more realistic forecasts of disease risk due to environmental change. It also can promote more effective vector control by both conventional and novel means.This study assessed the effect of particular plant species assemblages differing in nectar production on components of the vectorial capacity of the mosquito Anopheles gambiae s.s. , an important vector of African malaria.We followed cohorts of mosquitoes for three weeks in greenhouse mesocosms holding nectar-poor and nectar-rich plant species by tracking daily mortalities and estimating daily biting rates and fecundities...
March 2018: Journal of Applied Ecology
C O S Sorzano, E Fernández-Giménez, V Peredo-Robinson, J Vargas, T Majtner, G Caffarena, J Otón, J L Vilas, J M de la Rosa-Trevín, R Melero, J Gómez-Blanco, J Cuenca, L Del Cano, P Conesa, R Marabini, J M Carazo
The introduction of Direct Electron Detector (DED) videos in the Electron Microscope field has boosted Single Particle Analysis to a point in which it is currently considered to be a key technique in Structural Biology. In this article we introduce an approach to estimate the DED camera gain at each pixel from the movies themselves. This gain is needed to have the set of recorded frames into a coherent gray level range, homogeneous over the whole image. The algorithm does not need any other input than the DED movie itself, being capable of providing an estimate of the camera gain image, helping to identify dead pixels and cases of incorrectly calibrated cameras...
March 15, 2018: Journal of Structural Biology
Lilian O Guimarães, Francisco Fernandes, Eliana F Monteiro, Izilda Curado, Marcia M Holcman, Gerhard Wunderlich, Sidney E Santos, Júlia M Soler, Karin Kirchgatter
In low-endemic areas for malaria transmission, asymptomatic individuals play an important role as reservoirs for malarial infection. Understanding the dynamics of asymptomatic malaria is crucial for its efficient control in these regions. Genetic host factors such as Toll-like receptor (TLR) polymorphisms may play a role in the maintenance or elimination of infection. In this study, the effect of TLR polymorphisms on the susceptibility to malaria was investigated among individuals living in the Atlantic Forest of São Paulo, Southern Brazil...
March 15, 2018: Acta Tropica
Mauro E M Nunes, Talise E Müller, Camila Murussi, Aline M B Amaral, Jeane L C Gomes, Aline T Marins, Jossiele Leitemperger, Cintia C R Rodrigues, Tiago L Fiuza, Maiara D Costa, Eduardo S Severo, Denis B Rosemberg, Vania L Loro
The use of commercial pesticides combinations increases the risk of intoxication in non-target aquatic organisms. Here, we investigate the potential of a commercial pesticide formulation containing (CYP) plus chlopyrifos (CPF) to induce oxidative damage on two fish species (common carp and zebrafish). Carp and zebrafish were exposed for 96 h under laboratory conditions. Fish were divided in three different groups: CTL, 0.3 μg L-1 or 0.6 μg L-1 of CYP and 0.5 or 1 μg L-1 of CPF in commercial formulation...
March 15, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
M Rath, T R Mitchell, S E Gold
Volatile organic compounds (VOCs) produced by Plant Growth Promoting Rhizobacteria have recently been investigated due to their role in plant growth promotion and defense. Whereas some bacterial VOCs like 3-hydroxy-2-butanone (acetoin) and 2,3-butanediol produced by strains of Bacillus subtilis and Bacillus amyloliquefaciens promote plant growth, others like hydrogen cyanide and 3-phenylpropionic acid are phytotoxic, inhibiting plant growth. Bacillus mojavensis, a close relative of B. subtilis, is an endophytic bacterium of maize that has been shown to have antagonistic activity against the mycotoxigenic phytopathogen Fusarium verticillioides and growth promotion activity on maize seedlings...
March 2018: Microbiological Research
Colin K Skepper, Robert J Moreau, Brent A Appleton, Bret M Benton, Joseph E Drumm, Brian Y Feng, Mei Geng, Andreas Lingel, Yipin Lu, Mulugeta Mamo, Wosenu Mergo, Mina Mostafavi, Christopher M Rath, Micah Steffek, Kenneth T Takeoka, Kyoko Uehara, Lisha Wang, Jun-Rong Wei, Lili Xie, Wenjian Xu, Qiong Zhang, Cindy Li, Javier de Vicente
In the preceding manuscript we described a successful fragment-based lead discovery (FBLD) strategy for discovery of bacterial phosphopantetheine adenylyltransferase inhibitors (PPAT, CoaD). Following several rounds of optimization two promising lead compounds were identified: triazolopyrimidinone 3 and 4-azabenzimidazole 4. Here we disclose our efforts to further optimize these two leads for on-target potency and Gram-negative cellular activity. Enabled by a robust X-ray crystallography system, our structure-based inhibitor design approach delivered compounds with biochemical potencies 4-5 orders of magnitude greater than their respective fragment starting points...
March 18, 2018: Journal of Medicinal Chemistry
E Trybus, G Krol, T Obarzanowski, W Trybus, A Kopacz-Bednarska, M Obarzanowski, T Krol
Most studies on the effects of glucocorticosteroid therapy in rhinitis relate to their inhibitory effect on activation and the number of inflowing cells that are involved in the development and maintenance of inflammation. It is also very important to determine the range of effect of budesonide on residing cells (epithelial cells). The purpose of this study was to evaluate the effect of local budesonide therapy on the cytological image of the nasal mucosa, with attention paid to columnar cells in patients with rhinitis...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
K M Okoniewska, A E Kedzierska, J Okoniewski, A Slawek, K Grzymajlo, A Chelmonska-Soyta, T Grabowski
Epitopes of regulatory T cells (tregitopes) represent linear sequences of amino acids that induce CD4+ CD25+ Foxp3+ T lymphocytes expansion both in vitro and in vivo. The tregitopes' effectiveness was confirmed in autoimmune disease mouse models and in murine transplant models. Therefore, tregitopes together with regulatory T cells (Tregs) could play a major role in maintaining immune tolerance. The purpose of the presented study was a selection of potential tregitopes and assessment of their impact on Tregs expansion...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
L C Hewitt, I Z Inam, Y Saito, T Yoshikawa, A Quaas, A Hoelscher, E Bollschweiler, G E Fazzi, V Melotte, R E Langley, M Nankivell, D Cunningham, W Allum, G G Hutchins, H I Grabsch
BACKGROUND: Oesophageal (OeC) and gastric (GC) cancer patients are treated with similar multimodal therapy and have poor survival. There remains an urgent clinical need to identify biomarkers to individualise patient management and improve outcomes. Therapy with immune checkpoint inhibitors has shown promising results in other cancers. Proposed biomarkers to predict potential response to immune checkpoint inhibitors include DNA mismatch repair (MMR) and/or Epstein-Barr virus (EBV) status...
March 15, 2018: European Journal of Cancer
Diego L Lorca-Puls, Andrea Gajardo-Vidal, Jitrachote White, Mohamed L Seghier, Alexander P Leff, David W Green, Jenny T Crinion, Philipp Ludersdorfer, Thomas M H Hope, Howard Bowman, Cathy J Price
This study investigated how sample size affects the reproducibility of findings from univariate voxel-based lesion-deficit analyses (e.g., voxel-based lesion-symptom mapping and voxel-based morphometry). Our effect of interest was the strength of the mapping between brain damage and speech articulation difficulties, as measured in terms of the proportion of variance explained. First, we identified a region of interest by searching on a voxel-by-voxel basis for brain areas where greater lesion load was associated with poorer speech articulation using a large sample of 360 right-handed English-speaking stroke survivors...
March 14, 2018: Neuropsychologia
Anwar E Ahmed, Hamdan Al-Jahdali, Abeer N Alshukairi, Mody Alaqeel, Salma S Siddiq, Hanan A Alsaab, Ezzeldin A Sakr, Hamed A Alyahya, Munzir M Alandonisi, Alaa T Subedar, Nouf M Aloudah, Salim Baharoon, Majid A Alsalamah, Sameera Al Johani, Mohammed G Alghamdi
BACKGROUND: Rapidly and accurately identifying individuals who are at high risk for Middle East respiratory syndrome coronavirus (MERS-CoV) remains a major challenge for the medical and scientific communities. The aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of MERS-CoV infection in patients who had developed pneumonia. METHODS: A two-center retrospective case-control study was done, including 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by Real-time reverse-transcription polymerase chain reaction (rRT-PCR) from September 1, 2012 to June 1, 2016 at King Abdulaziz Medical City in Riyadh (KAMC-R) and King Fahd General Hospital in Jeddah (KFGH-JED)...
March 14, 2018: International Journal of Infectious Diseases: IJID
P Collinet, X Fritel, C Revel-Delhom, M Ballester, P A Bolze, B Borghese, N Bornsztein, J Boujenah, N Bourdel, T Brillac, N Chabbert-Buffet, C Chauffour, N Clary, J Cohen, C Decanter, A Denouël, G Dubernard, A Fauconnier, H Fernandez, T Gauthier, F Golfier, C Huchon, G Legendre, J Loriau, E Mathieu-d'Argent, B Merlot, J Niro, P Panel, P Paparel, C A Philip, S Ploteau, C Poncelet, B Rabischong, H Roman, C Rubod, P Santulli, M Sauvan, I Thomassin-Naggara, A Torre, J M Wattier, C Yazbeck, M Canis
First-line investigations to diagnose endometriosis are clinical examination and pelvic ultrasound. Second-line investigations include pelvic examination performed by a referent clinician, transvaginal ultrasound performed by a referent, and pelvic MRI. It is recommended to treat endometriosis when it is symptomatic. First-line hormonal treatments recommended for the management of painful endometriosis are combined hormonal contraceptives or levonorgestrel 52mg IUD. There is no evidence to recommend systematic preoperative hormonal therapy for the unique purpose of preventing the risk of surgical complications or facilitating surgery...
March 14, 2018: Gynecologie, Obstetrique, Fertilite & Senologie
Michael E Zilm, Le Yu, William A Hines, Mei Wei
A detailed magnetization study, along with an assessment of the cellular proliferation, has been carried out on transition-metal-doped hydroxyapatite (HA), Ca10-x Mx (PO4 )6 (OH)2 , where M = Mn, Co, and Fe. In particular, a series of MnHA powder samples with an x value of 0.04 ≤ x ≤ 1.21, one CoHA (x = 0.48) and one FeHA sample (x = 1.06) were synthesized using a wet chemical method along with an ion-exchange procedure. Characterization by transmission electron microscope (TEM), energy-dispersive X-ray spectroscopy (EDXS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) indicated that the substitution of M elements does not change the morphology and crystalline structure of pure HA that showing a single phased HA nano-rod...
June 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Christophe O Chantre, Patrick H Campbell, Holly M Golecki, Adrian T Buganza, Andrew K Capulli, Leila F Deravi, Stephanie Dauth, Sean P Sheehy, Jeffrey A Paten, Karl Gledhill, Yanne S Doucet, Hasan E Abaci, Seungkuk Ahn, Benjamin D Pope, Jeffrey W Ruberti, Simon P Hoerstrup, Angela M Christiano, Kevin Kit Parker
Wounds in the fetus can heal without scarring. Consequently, biomaterials that attempt to recapitulate the biophysical and biochemical properties of fetal skin have emerged as promising pro-regenerative strategies. The extracellular matrix (ECM) protein fibronectin (Fn) in particular is believed to play a crucial role in directing this regenerative phenotype. Accordingly, Fn has been implicated in numerous wound healing studies, yet remains untested in its fibrillar conformation as found in fetal skin. Here, we show that high extensional (∼1...
March 5, 2018: Biomaterials
Jonathan P Cranford, Thomas J O'Hara, Christopher T Villongco, Omar M Hafez, Robert C Blake, Joseph Loscalzo, Jean-Luc Fattebert, David F Richards, Xiaohua Zhang, James N Glosli, Andrew D McCulloch, David E Krummen, Felice C Lightstone, Sergio E Wong
Patient-specific models of the ventricular myocardium, combined with the computational power to run rapid simulations, are approaching the level where they could be used for personalized cardiovascular medicine. A major remaining challenge is determining model parameters from available patient data, especially for models of the Purkinje-myocardial junctions (PMJs): the sites of initial ventricular electrical activation. There are no non-invasive methods for localizing PMJs in patients, and the relationship between the standard clinical ECG and PMJ model parameters is underexplored...
March 16, 2018: Cardiovascular Engineering and Technology
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