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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
Rekha Seshadri, Sinead C Leahy, Graeme T Attwood, Koon Hoong Teh, Suzanne C Lambie, Adrian L Cookson, Emiley A Eloe-Fadrosh, Georgios A Pavlopoulos, Michalis Hadjithomas, Neha J Varghese, David Paez-Espino, Rechelle Perry, Gemma Henderson, Christopher J Creevey, Nicolas Terrapon, Pascal Lapebie, Elodie Drula, Vincent Lombard, Edward Rubin, Nikos C Kyrpides, Bernard Henrissat, Tanja Woyke, Natalia N Ivanova, William J Kelly
Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions...
March 19, 2018: Nature Biotechnology
Xiaosa Li, Ying Wang, Yajing Liu, Bei Yang, Xiao Wang, Jia Wei, Zongyang Lu, Yuxi Zhang, Jing Wu, Xingxu Huang, Li Yang, Jia Chen
The targeting range of CRISPR-Cas9 base editors (BEs) is limited by their G/C-rich protospacer-adjacent motif (PAM) sequences. To overcome this limitation, we developed a CRISPR-Cpf1-based BE by fusing the rat cytosine deaminase APOBEC1 to a catalytically inactive version of Lachnospiraceae bacterium Cpf1. The base editor recognizes a T-rich PAM sequence and catalyzes C-to-T conversion in human cells, while inducing low levels of indels, non-C-to-T substitutions and off-target editing.
March 19, 2018: Nature Biotechnology
Jonathan T Ting, Brian R Lee, Peter Chong, Gilberto Soler-Llavina, Charles Cobbs, Christof Koch, Hongkui Zeng, Ed Lein
This protocol is a practical guide to the N-methyl-D-glucamine (NMDG) protective recovery method of brain slice preparation. Numerous recent studies have validated the utility of this method for enhancing neuronal preservation and overall brain slice viability. The implementation of this technique by early adopters has facilitated detailed investigations into brain function using diverse experimental applications and spanning a wide range of animal ages, brain regions, and cell types. Steps are outlined for carrying out the protective recovery brain slice technique using an optimized NMDG artificial cerebrospinal fluid (aCSF) media formulation and enhanced procedure to reliably obtain healthy brain slices for patch clamp electrophysiology...
February 26, 2018: Journal of Visualized Experiments: JoVE
Youn Young Shim, Rana Mustafa, Jianheng Shen, Kornsulee Ratanapariyanuch, Martin J T Reaney
Chickpea and other pulses are commonly sold as canned products packed in a thick solution or a brine. This solution has recently been shown to produce stable foams and emulsions, and can act as a thickener. Recently interest in this product has been enhanced through the internet where it is proposed that this solution, now called aquafaba by a growing community, can be used a replacement for egg and milk protein. As aquafaba is both new and being developed by an internet based community little is known of its composition or properties...
February 10, 2018: Journal of Visualized Experiments: JoVE
Jacey L Janz Vernoski, Jack R Bjorkland, Talia J Kramer, Steven T Oczak, Alexandra L Borstad
Proprioception may be the least well measured of all contributors to the neural control of movement. New precise, reliable measures of proprioception are needed for clinical diagnosis of impairment, and to measure outcomes of proprioceptive training. The purpose of this simple, non-invasive method is to temporarily knockdown upper limb proprioception in healthy adults, to an extent that would be useful in the development and testing of upper limb proprioception measures. Knockdown models have two main advantages over studying humans with impaired proprioception: participant availability and the ability to control the extent of impairment across participants...
March 3, 2018: Journal of Visualized Experiments: JoVE
Wilhelm H Flatz, Annika Henneberger, Maximilian F Reiser, Robert Gürkov, Birgit Ertl-Wagner
Analysis of neural structures in Menière's Disease (MD) is of importance, since a loss of such structures has previously been proposed for this patient group but has yet to be confirmed. This protocol describes a method of in vivo evaluation of neural changes especially well suitable for cranial nerve analysis using magnetic resonance imaging (MRI). MD-patients and normal hearing persons were examined in a 3-T MR-scanner using a scan protocol including strongly T2-weighted 3D gradient-echo-sequence (3D-CISS)...
February 21, 2018: Journal of Visualized Experiments: JoVE
Clémence Granier, Emeline Vinatier, Elia Colin, Marion Mandavit, Charles Dariane, Virginie Verkarre, Lucie Biard, Rami El Zein, Corinne Lesaffre, Isabelle Galy-Fauroux, Hélène Roussel, Eléonore De Guillebon, Charlotte Blanc, Antonin Saldmann, Cécile Badoual, Alain Gey, Éric Tartour
Immune cells are important components of the tumor microenvironment and influence tumor growth and evolution at all stages of carcinogenesis. Notably, it is now well established that the immune infiltrate in human tumors can correlate with prognosis and response to therapy. The analysis of the immune infiltrate in the tumor microenvironment has become a major challenge for the classification of patients and the response to treatment. The co-expression of inhibitory receptors such as Program Cell Death Protein 1 (PD1; also known as CD279), Cytotoxic T Lymphocyte Associated Protein 4 (CTLA-4), T-Cell Immunoglobulin and Mucin Containing Protein-3 (Tim-3; also known as CD366), and Lymphocyte Activation Gene 3 (Lag-3; also known as CD223), is a hallmark of T cell exhaustion...
February 8, 2018: Journal of Visualized Experiments: JoVE
Mireille Laforge, Ricardo Silvestre, Vasco Rodrigues, Julie Garibal, Laure Campillo-Gimenez, Shahul Mouhamad, Valérie Monceaux, Marie-Christine Cumont, Henintsoa Rabezanahary, Alain Pruvost, Anabela Cordeiro-da-Silva, Bruno Hurtrel, Guido Silvestri, Anna Senik, Jérôme Estaquier
Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preservation of CD4+/CD8+ T cell ratio in lymphoid organs and in the gut, (c) maintenance of memory CD4+ T cells, and (d) increased specific CD4+ T cell response associated with the expression of cytotoxic molecules...
March 19, 2018: Journal of Clinical Investigation
Zaher Nazzal, Hisham Sholi, Suha B Sholi, Mohammad B Sholi, Rawya Lahaseh
BACKGROUND: Mammography screening is an effective tool for early detection and management of breast cancer. Female health-care workers' awareness of breast cancer screening is important because their beliefs and behaviours could influence other women. The aim of this study was to assess mammography screening uptake by female health-care workers at primary health-care centres and to identify the primary motivators and barriers that affect uptake. METHODS: This cross-sectional study included all governmental primary health-care centres in the West Bank...
February 21, 2018: Lancet
Rola Abu Dalfa, Khaled I Abu El Aish, Mohamed El Raai, Nermeen El Gazaly, Ahmed Shatat
BACKGROUND: Diarrhoea causes 15% of under-5 mortality in developing countries. Zinc (Zn) stores in the body are known to be depleted during acute diarrhoea. The aim of this study was to evaluate the efficacy of Zn given with standard treatment to children with acute or moderate diarrhoea. METHODS: In this quasi-unmasked, parallel-group study, we enrolled children with diarrhoea at El-Dorra Paediatric Hospital, Gaza Strip, occupied Palestinian territory. Inclusion criteria were children with more than three unformed stools in the preceding 24 h, duration of diarrhoea up to 72 h, and ability to accept oral fluids or feeds...
February 21, 2018: Lancet
Raed Tafish, Khaled I Abu El Aish, Walid Madi
BACKGROUND: General anaesthesia and spinal anaesthesia are commonly used for caesarean sections. The aim of this study was to compare the outcomes from caesarean sections with these two types of anaesthesia. METHODS: In this quasi-controlled trial, we enrolled women undergoing caesarean sections at Al-Helal Al-Emirati Hospital, Rafah, Gaza Strip. Women were assigned either to general anaesthesia (20% intravenous propofol for anaesthesia induction followed by atracurium for muscle relaxation, and nitrous oxide and oxygen for anaesthesia maintenance) or to spinal anaesthesia (0·5% hyperbaric solution bupivacaine with 20 μg fentanyl intrathecally)...
February 21, 2018: Lancet
Khaled Abu El Aish, Raed Tafish, Haly Zourob
BACKGROUND: Finding appropriate analgesics is important for a mother's recovery after a caesarean section. The aim of this study was to compare the analgesic effect of spinal morphine and fentanyl for women undergoing a caesarean section. METHODS: In this randomised, unmasked, parallel-group, controlled trial, eligible participants were women undergoing caesarean section with spinal anaesthetic at the Al-Helal Al-Emirati Hospital, Rafah, Gaza Strip, occupied Palestinian territory...
February 21, 2018: Lancet
Elham Kateeb, Elizabeth Momany
BACKGROUND: Beliefs about oral health during pregnancy demographic factors, such as level of education and socioeconomic status, are associated with an increased risk of oral diseases during pregnancy. The aim of this study was to assess the oral health status of pregnant women and the relation to the women's oral health knowledge, beliefs, behaviour, and access to dental care. METHODS: For this cross-sectional study, pregnant women visiting pre-natal care clinics at the Palestinian Ministry of Health centres in the Jerusalem governorate were invited to complete a structured interview with questions about beliefs about oral health care and their oral hygiene practices...
February 21, 2018: Lancet
Angélique Rousseau, Stéphanie La Carbona, Aurélien Dumètre, Lucy J Robertson, Gilles Gargala, Sandie Escotte-Binet, Loïc Favennec, Isabelle Villena, Cédric Gérard, Dominique Aubert
Giardia duodenalis, Cryptosporidium spp. and Toxoplasma gondii are protozoan parasites that have been highlighted as emerging foodborne pathogens by the Food and Agriculture Organization of the United Nations and the World Health Organization. According to the European Food Safety Authority, 4786 foodborne and waterborne outbreaks were reported in Europe in 2016, of which 0.4% were attributed to parasites including Cryptosporidium, Giardia and Trichinella. Until 2016, no standardized methods were available to detect Giardia, Cryptosporidium and Toxoplasma (oo)cysts in food...
2018: Parasite: Journal de la Société Française de Parasitologie
Jessica L Combs, Elizabeth N Riley, Sarah J Peterson, Carol E Jordan, Gregory T Smith
OBJECTIVE: Exposure to sexual assault results in ongoing harms for women. After an assault, some women engage in higher levels of externalizing behaviors, such as problem drinking, and others experience higher levels of internalizing dysfunction, such as symptoms of anxiety and depression. We sought to understand the role of premorbid factors on the different post-assault experiences of women. METHOD: We studied 1,929 women prospectively during a period of high risk for sexual assault (the first year of college): women were assessed in July before arriving at college and in April near the end of the school year...
March 2018: Journal of Studies on Alcohol and Drugs
Emily T Noyes, Jacob A Levine, Robert C Schlauch, Cory A Crane, Gerard J Connors, Stephen A Maisto, Ronda L Dearing
OBJECTIVE: With the growing recognition that, for some, significant changes in drinking occur before the first treatment session (i.e., pretreatment change), researchers have called for the careful assessment of when change occurs and its potential impact on mechanism of behavior change (MOBC) research. Using a commonly hypothesized MOBC variable, alcohol abstinence self-efficacy, the primary aim of this study was to examine the effect of pretreatment change on the study of MOBCs. METHOD: Sixty-three individuals diagnosed with alcohol dependence were recruited to participate in a 12-week cognitive-behavioral treatment...
March 2018: Journal of Studies on Alcohol and Drugs
Sandra N Bulens, Sarah H Yi, Maroya S Walters, Jesse T Jacob, Chris Bower, Jessica Reno, Lucy Wilson, Elisabeth Vaeth, Wendy Bamberg, Sarah J Janelle, Ruth Lynfield, Paula Snippes Vagnone, Kristin Shaw, Marion Kainer, Daniel Muleta, Jacqueline Mounsey, Ghinwa Dumyati, Cathleen Concannon, Zintars Beldavs, P Maureen Cassidy, Erin C Phipps, Nicole Kenslow, Emily B Hancock, Alexander J Kallen
In healthcare settings, Acinetobacter spp. bacteria commonly demonstrate antimicrobial resistance, making them a major treatment challenge. Nearly half of Acinetobacter organisms from clinical cultures in the United States are nonsusceptible to carbapenem antimicrobial drugs. During 2012-2015, we conducted laboratory- and population-based surveillance in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee to determine the incidence of carbapenem-nonsusceptible A...
April 2018: Emerging Infectious Diseases
Mie Ikeda, Megumi Kaneko, Shin-Ichiro Tachibana, Betty Balikagala, Miki Sakurai-Yatsushiro, Shouki Yatsushiro, Nobuyuki Takahashi, Masato Yamauchi, Makoto Sekihara, Muneaki Hashimoto, Osbert T Katuro, Alex Olia, Paul S Obwoya, Mary A Auma, Denis A Anywar, Emmanuel I Odongo-Aginya, Joseph Okello-Onen, Makoto Hirai, Jun Ohashi, Nirianne M Q Palacpac, Masatoshi Kataoka, Takafumi Tsuboi, Eisaku Kimura, Toshihiro Horii, Toshihiro Mita
Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014-2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage-specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates...
April 2018: Emerging Infectious Diseases
Natasha A Lannin, Louise Ada, Coralie English, Julie Ratcliffe, Maria Crotty
Rationale Although clinical practice guidelines recommend that management of moderate to severe spasticity include the use of botulinum toxin-A in conjunction with therapy, there is currently no evidence to support the addition of therapy. Aims To determine the effect and cost-benefit of adding evidence-based movement training to botulinum toxin-A. Sample size estimate A total of 136 participants will be recruited in order to be able to detect a between-group difference of seven points on the Goal Attainment Scale T-score with 80% power at a two-tailed significance level of 0...
January 1, 2018: International Journal of Stroke: Official Journal of the International Stroke Society
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