Amplified antimicrobial action of chlorhexidine encapsulated in PDAC-functionalized acrylate copolymer nanogel carriers

We have developed and tested a novel functionalised nanocarrier for chlorhexidine (CHX) which provides a very strong enhancement of its antimicrobial action. The nanocarrier was based on lightly-cross-linked acrylate copolymer nanogel particles loaded with CHX followed by a surface functionalisation with the cationic polyelectrolyte poly(diallyldimethylammonium chloride (PDAC). We explored the antimicrobial effect of the PDAC-coated CHX-loaded nanogel carriers on E. coli, S. auresus, C. cerevisiae and C. reinhardtii and discovered that it is much higher than that of solution with equivalent overall concentration of free CHX. Our experiments also showed a marked increase of the cationic CHX-loaded nanocarriers antimicrobial action on these microorganisms at shorter incubation times compared with the non-coated CHX-loaded nanogel particles at the same CHX concentration and other conditions. We attribute the increase in the antimicrobial activity of the cationically-functionalised nanogel carrier to its electrostatic adhesion to the microbial cells walls which allows much higher CHX concentration to be delivered directly onto the cell surface. The results of this study can be used for development of novel more efficient antialgal, antifungal and antbacterial formulations based on cationically functionalised nanogels. Our method can also be used for boosting the effect of other cationic antimicrobial agents by encapsulating them in cationically-functionalised nanogel carriers. This nanotechnological approach could lead to developing more effective antimicrobial and disinfecting agents, dental formulations for plaque control, wound dressings, antialgal/antibiofouling formulations and novel antifungal agents

Short intense ion pulses for materials and warm dense matter research

We have commenced experiments with intense short pulses of ion beams on the Neutralized Drift Compression Experiment-II at Lawrence Berkeley National Laboratory, by generating beam spots size with radius r < 1 mm within 2 ns FWHM and approximately 10^10 ions/pulse. To enable the short pulse durations and mm-scale focal spot radii, the 1.2 MeV Li+ ion beam is neutralized in a 1.6-meter drift compression section located after the last accelerator magnet. An 8-Tesla short focal length solenoid compresses the beam in the presence of the large volume plasma near the end of this section before the target. The scientific topics to be explored are warm dense matter, the dynamics of radiation damage in materials, and intense beam and beam-plasma physics including selected topics of relevance to the development of heavy-ion drivers for inertial fusion energy. Here we describe the accelerator commissioning and time-resolved ionoluminescence measurements of yttrium aluminium perovskite using the fully integrated accelerator and neutralized drift compression components.Comment: 7 pages, 9 figure

Tissue tolerance: an essential but elusive trait for salt-tolerant crops

For a plant to persist in saline soil, osmotic adjustment of all plant cells is essential. The more salt-tolerant species accumulate Na+ and Cl– to concentrations in leaves and roots that are similar to the external solution, thus allowing energy-efficient osmotic adjustment. Adverse effects of Na+ and Cl– on metabolism must be avoided, resulting in a situation known as ‘tissue tolerance’. The strategy of sequestering Na+ and Cl– in vacuoles and keeping concentrations low in the cytoplasm is an important contributor to tissue tolerance. Although there are clear differences between species in the ability to accommodate these ions in their leaves, it remains unknown whether there is genetic variation in this ability within a species. This viewpoint considers the concept of tissue tolerance, and how to measure it. Four conclusions are drawn: (1) osmotic adjustment is inseparable from the trait of tissue tolerance; (2) energy-efficient osmotic adjustment should involve ions and only minimal organic solutes; (3) screening methods should focus on measuring tolerance, not injury; and (4) high-throughput protocols that avoid the need for control plants and multiple Na+ or Cl- measurements should be developed. We present guidelines to identify useful genetic variation in tissue tolerance that can be harnessed for plant breeding of salt tolerance

Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD

BACKGROUND: A new locus for amyotrophic lateral sclerosis – frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p. METHODS: We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus. RESULTS: Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 (F476), but no mutation was detected within IFT74 in family 2 (F2). While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids) led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420). An additional sequence variant (G58D) was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples. CONCLUSION: Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

The effects of acute dopamine reuptake inhibition on cognitive function during passive hyperthermia

Dopamine activity can modulate physical performance in the heat, but less is known about its effects on cognition during thermal stress. Twelves males completed a randomized, double-blinded protocol consisting of oral ingestion of 20 mg of methylphenidate (MPH) or placebo (lactose pill) during passive heating using a water-perfused suit (water temperature ~49C). To identify the impact of peripheral versus central thermal strain, a cognitive test battery was completed at four different thermal states: baseline (BASE; 37.20.6˚C core, 32.90.7˚C skin), neutral core-hot skin (NC-HS; 37.20.3˚C, 37.40.3˚C), hyperthermic core-hot skin (HC-HS; 38.70.4˚C, 38.70.2˚C), and hyperthermic core-cooled skin (HC-CS; 38.50.4˚C, 35.10.8˚C). The cognitive test battery consisted of the 2-back task (i.e. working memory), set-shifting (i.e. executive function), Groton Maze Learning Task (i.e. executive function) and detection task (i.e. psychomotor processing). MPH led to significantly higher heart rates (~5-15 bmin-1) at BASE, NC-HS, and HC-HS (all pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Ameliorating The Effects Of The Digenetic Trematode, \u3ci\u3eBolbophorus damnificus\u3c/i\u3e On The Channel Catfish Industry

In the middle to late 1990s, an emerging digenetic trematode problem was recognized in the channel catfish industry. Morphologic and molecular analysis identified the culprit as Bolbophorns damnificus. The American White Pelican, Pelecanus erythrorhynchos serves as the definitive host, while the marsh rams-horn snail (Planorbella trivolvis) is the first intermediate host. Diagnosis of an infection involves identifying the metacercariae in the subcutaneous tissues. Infestations can be life threatening to catfish fingerlings but the proximate cause of mortality has not been ascertained. They may also predispose fingerlings to secondary infections. Larger fish do not usually succumb to the infestation, but have poor production thus posing significant economic losses. Current methods of control (biological and chemical) have centered on eradication of the snail host. Chemical control includes shoreline treatments using copper sulfate or hydrated lime. This information is the result of multi-institutional and multidisciplinary efforts that have been expended to identify and explore the pathobiology of the parasite as well as its intermediate and final hosts