bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gout and hyperuricaemia in the USA: prevalence and trends
Authors: Singh Gurkirpal , Lingala Bharathi , Mithal Alka 
Published: April 2019

Abstract

Objectives
Several recent observations have suggested that the prevalence of gout may be increasing worldwide, but there are no recent data from the USA. We analysed the prevalence of hyperuricaemia and gout in the US population from 2007–08 to 2015–16.

Methods
We studied adults ⩾20 years of age from the National Health and Nutrition Examination Survey from 2007–08 to 2015–16. Persons with gout were identified from the home interview question ‘Has a doctor or other health professional ever told you that you had gout?’ Hyperuricaemia was defined as a serum urate level >0.40 mmol/l (6.8 mg/dl) (supersaturation levels at physiological temperatures and pH).

Results
In 2015–16, the overall prevalence of gout among US adults was 3.9%, corresponding to a total affected population of 9.2 million. Hyperuricaemia (>0.40 mmol/l or 6.8 mg/dl) was seen in 14.6% of the US population (estimated 32.5 million individuals). No significant trends were identified in the age-adjusted prevalence of gout and hyperuricaemia. Statistical comparisons between 2007–08 and 2015–16 age-adjusted rates were not significant.

Conclusion
While the age-adjusted prevalence of gout and hyperuricaemia has remained unchanged in the most recent decade from 2007–08 to 2015–16, the estimated total number of persons with self-reported gout has increased from 8.3 million to 9.2 million. The age-adjusted prevalence of hyperuricaemia has declined slightly, but the total number of affected individuals is virtually identical (32.5 million in 2015–16 compared with 32.1 million in 2007–08).
Tuck-In Tenon Patch Graft in Corneal Perforation
Authors: Sharma Namrata , Singhal Deepali , Maharana Prafulla Kumar , Vajpayee Rasik B. 
Published: April 2019

Purpose:
To describe the outcomes of tuck-in tenon patch graft (TPG) in the management of corneal perforation up to 5-mm size.

Methods:
Thirty-one cases of sterile corneal perforation (3–5 mm) underwent autologous TPG. The technique included, freshening of the edges, measuring the size of defect, creating a 360-degree stromal pocket around the perforation margin, harvesting the tenon graft followed by tucking into the stromal pocket, and application of cyanoacrylate glue or suturing the graft using 10-0 monofilament nylon suture. The main outcome measure was rate of healing (percentage of cases healed).

Results:
The mean age was 52.3 ± 8.9 years with 22 male and 9 female patients. The various etiologies of corneal perforation included trauma (n = 10), neurotrophic keratitis (n = 11), and peripheral ulcerative keratitis (n = 10). The mean size of corneal perforation was 4.2 ± 0.6 mm (range 3–5 mm). The mean duration of epithelial healing was 25.7 ± 6.7 days. Best-corrected visual acuity improved from 1.8 ± 0.4 to 1.2 ± 0.4 logarithm of the minimum angle of resolution units at 4 weeks after surgery (P ≤ 0.01). Twenty-seven (87.1%) cases healed with formation of a leucomatous scar at 16.9 ± 2.7 weeks, whereas 4 cases had a flat anterior chamber. In three-fourths of the cases, a corneal graft was performed. In one case, graft resuturing was performed for post-op aqueous leak, which healed with the formation of a corneo-iridic scar.

Conclusions:
TPG is a safe, simple, inexpensive, and an effective technique for the management of corneal perforations. The advantages include the autologous nature of the graft, cost effectiveness, and easy availability.
Hepatitis C therapy with direct antiviral agents in patients with advanced chronic kidney disease: real-world experience of the German Hepatitis C-Registry (Deutsches Hepatitis C-Register)
Authors: Wiegand Johannes , Buggisch Peter , Mauss Stefan , Boeker Klaus H.W. , Klinker Hartwig , Müller Tobias , Günther Rainer , Serfert Yvonne , Manns Michael P. , Zeuzem Stefan , Berg Thomas , Hinrichsen Holger , C-Registry German Hepatitis 
Published: April 2019

Background
Direct-acting antiviral agents (DAAs) have revolutionized treatment of chronic hepatitis C in patients with normal glomerular filtration rate (GFR). However, patients with impaired kidney function have been excluded from several clinical trials. We, therefore, investigated the use, effectiveness, and tolerability of DAAs in patients with GFR less than 30 ml/min in the real-world setting.

Patients and methods
An analysis was done within the German Hepatitis C-Registry on 5733 patients including 46 individuals with a baseline GFR less than 30 ml/min treated with sofosbuvir-based (61%) or paritaprevir/ritonavir-based (39%) regimens.

Results
Sustained virological response 12 rates did not differ significantly between patients with baseline GFR less than 30 versus more than 30 ml/min (91 vs. 96%). Nine individuals with a baseline GFR more than 30 ml/min presented with a GFR less than 30 ml/min at the end of treatment. GFR improvement from less than 30 ml/min to more than 30 ml/min was observed in 9/46 cases. Adverse events did not differ in patients with GFR less than 30 versus more than 30 ml/min. However, serious adverse events were significantly more frequent in individuals with GFR less than 30 ml/min and associated with ribavirin.

Conclusion
Different DAA therapies can be safely used with high sustained virological response rates in patients with GFR less than 30 ml/min. Ribavirin has to be avoided because of poor tolerability.
Utility of Metabolic Parameters on FDG PET/CT in the Classification of Early-Stage Lung Adenocarcinoma
Authors: Iwano Shingo , Ito Shinji , Kamiya Shinichiro , Ito Rintaro , Kato Katsuhiko , Naganawa Shinji 
Published: April 2019

PurposeThis paper aims to explore the role of a metabolic parameter on18F-FDG-PET/CT for clinical T-classification in early-stage adenocarcinoma.Patients and MethodsOne hundred six surgically resected pathological TNM stage (p-stage) 0/I lung adenocarcinomas were retrospectively reviewed. The solid size (SS) measured on thin-section CT and the pathological invasive size (IS) of tumors were recorded. The SUVmax and metabolic tumor volume with SUV ≥1.0 (MTV1.0) derived from PET/CT data were measured on a workstation, and the metabolic tumor diameter with SUV ≥1.0 (MTD1.0) was calculated automatically from MTV1.0. For the correlations between the IS and the SS, MTD1.0, or SUVmax, Pearson's correlation coefficients were compared using the Meng-Rosenthal-Rubin method. Additionally, the reproducibility between the clinical TNM stage (c-stage), based on the SS or MTD1.0, and the p-stage was analyzed using the kappa coefficient (k).ResultsFor the correlations between the IS and the other parameters, Pearson correlation coefficient was 0.630 for the SS, 0.600 for the SUVmax, and 0.725 for MTD1.0. MTD1.0correlated significantly and more strongly with the IS than the SS and the SUVmax did (P= 0.040, andP= 0.008, respectively). The reproducibility between p-stage and c-stage based on the SS was moderate (k = 0.529,P< 0.001), whereas that between p-stage and c-stage based on MTD1.0was substantial (k = 0.676,P< 0.001).ConclusionsMTD1.0on FDG-PET/CT was correlated significantly and more strongly with the pathological IS in lung adenocarcinomas than with the SS on thin-section CT. FDG-PET/CT could classify more precisely early-stage lung adenocarcinoma than the presently used T-classification based on thin-section CT findings.
Antimicrobial activity of Zamzam water against Salmonella typhii
in vitro
Authors: Utami Amalia Tri 
Published: April 2019

Objective
To determine the antimicrobial effect of zam zam water against Salmonella typhi in vitro. The antimicrobial effect was measured from the minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of zamzam water against Salmonella typhi.

Design
This experimental study used post-test only control group design with four time repetition. Step one was cultivating bacteria in liquid medium with various concentration of extract, that was 1 %, 1.25 %, 1.5 %, 1.75 %, 2 % with two control, extract control and bacterial control.

Results
The MIC (Minimal Inhibition Concentration) is 1.5 % concentration of extract. Step two was plating in NAP (Nutrient Agar Plate) medium. The MBC (Minimal Bactericidal Concentration) is 1.75 % concentration of zamzam water. The result of experiment was knew there are different average of Salmonella typhi colony from every group. The result experiment was analyzed by One Way Anova Test. The hypothesis test of MBC show significant differentiation, and then was continued with regression test. The conclusion of this study was zamzam water have antimicrobial activity against Salmonella typhii
in vitro.
Genomic analysis of Burkholderia ambifaria identifies key specialised metabolites for biopesticidal applications
Authors: Mullins Alex , Murray James , Bull Matthew , Jenner Matthew , Jones Cerith , Webster Gordon , Green Angharad , Neill Daniel , Connor Thomas , Parkhill Julian , Challis Gregory , Mahenthiralingam Eshwar 
Published: April 2019

Background

Burkholderia bacteria are renowned for the biosynthesis of an extensive repertoire of specialised metabolites encoded by biosynthetic gene clusters (BGCs). Burkholderia ambifaria is a historical biopesticide and produces multiple antimicrobials with activity against nematodes, fungi and bacteria. We evaluated the distribution of antimicrobial activity and BGCs across the species which, despite their biopesticidal potency, is poorly understood.

Results
Genomic analysis of 64-B. ambifaria whole-genomes revealed considerable diversity. Pathway prediction identified 1272 BGCs across 64 strains that were de-replicated to 38 distinct BGCs. Known BGCs accounted for 13 of the BGCs; 7 of which corresponded to known antimicrobials, and included enacyloxins and bactobolins. The antimicrobial activity of the strains was assessed in a classical overlay assay against animal and plant pathogens. The combined genome mining and in vitro activity screens identified a potent anti-Gram-positive and anti-Oomycete compound, cepacin. A damping-off disease model with the pathogen Pythium ultimum and legume Pisum sativum (garden peas) highlighted cepacin as a key specialised metabolite in crop protection. B. ambifaria strain persistence in a mouse inhalation infection model was reduced by removal of the third replicon, whilst retaining the biopesticidal properties of the B. ambifaria strain.

Conclusion
This work highlights the diversity and prevalence of specialised metabolites in B. ambifaria, and the importance of the potent antimicrobial cepacin in protection against damping-off disease in agriculture. Construction of a B. ambifaria strain that retained biopesticidal properties yet was attenuated for persistence within a murine infection model provides a potential route towards developing safe biopesticidal agent.
Global gene expression profiling of a virulent Klebsiella pneumoniae strain during pulmonary infection
Authors: Kidd Timothy , Dumigan Amy , Forde Brian , Phan Minh-Duy , Canals Rocio , Hinton Jay , Schembri Mark , Bengoechea Jose 
Published: April 2019

Background

Klebsiella pneumoniae (Kpn) is an important respiratory pathogen associated with significant mortality, fierce inflammatory responses and high rates of antimicrobial resistance. The increasing incidence of multidrug resistant Kpn has significantly narrowed the therapeutic options available; as such, there is an urgent need to better understand Kpn pathophysiology to identify novel therapeutic targets. Here we performed an in vivo transcriptomic analysis of Kpn isolated from a mammalian host with pulmonary infection.

Methods
C57BL/6 mice were intranasally inoculated with the virulent Kp52.145 strain (serotype O1:K2); with lungs extracted, homogenised and pooled (n=3; in duplicate) at 32 h post-infection for bacterial RNA purification and RNA-Seq (Illumina). Differential gene expression (analysed using Degust [Voom/Limma]; FDR cut-off =0.01, abs log-FC=2) was assessed in comparison with mid-log phase growth in Lennox broth.

Results
Overall, we identified >900 differentially expressed genes (DEGs), comprising ∼17 % of the combined chromosomal and plasmid coding sequence repertoire. 52 % of the DEGs were upregulated during infection, including several siderophore-independent iron-, manganese- and zinc-uptake systems (e.g. hmuRSTUV, sitABCD, mntH and znuACB). We also observed a marked in vivo oxidative stress signal, with several Kpn oxidative stress response genes (e.g. oxyR, katE, katG) upregulated during infection. In contrast, expression of mgrB, a negative-regulator of the PhoPQ two-component system associated with resistance to host antimicrobial peptides was downregulated.

Conclusion
This study provides a novel insight into Kpn gene expression during pulmonary infection. Overall, our data suggest that adaptation to metal starvation, oxidative stress and innate immune defenses are critical for the success of Kpn lung infection.
HIV-1 infectivity of cells is enhanced at mitosis: a role for Vpr?
Authors: Gibbons Joseph , Lee Wing-yiu Jason , McKnight Áine 
Published: April 2019

Restriction factors are present in all cells including non-immune cells and protect them from invading viruses. RNA-associated Early-stage Antiviral Factor (REAF) was identified from a whole genome siRNA screen for restriction factors to HIV-1(1). siRNA induced knockdown of REAF increases viral infectivity, while over-expression of the protein limits infection(2). Here we show that during mitosis, REAF is specifically excluded from the chromatin region and that mitotic cells have an increased susceptibility to HIV-1. We also demonstrate that in HIV-1 infection of monocyte-derived macrophages, Vpr is responsible for the degradation of nuclear REAF. Furthermore, silencing REAF expression in cycling cells by RNAi causes cells to accumulate in the G2/M phase. This result is consistent with previous observations that Vpr induces cell cycle arrest after infection (3).
1. L. Liu et al., A whole genome screen for HIV restriction factors. Retrovirology 8, 94 (2011).
2. K. M. Marno et al., Novel restriction factor RNA-associated early-stage anti-viral factor (REAF) inhibits human and simian immunodeficiency viruses. Retrovirology 11, 3 (2014).
3. J. B. Jowett et al., The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2+M phase of the cell cycle. J Virol 69, 6304–6313 (1995).
Drug delivery to rodents: how to deal with body mass and water intake fluctuations?
Authors: Leidyanne Ferreira Gonçalves , Caroline Fernandes-Santos 
Published: April 2019

ABSTRACTIntroductionAnimal models are used to test the safety and efficacy of drugs. They are often administered to rodents in the drinking water, but it has some limitations, such as the drug stability, variations of water consumption and body mass. We investigated telmisartan (TEL) stability in mice drinking water by UV spectrophotometry, and if water intake and body mass fluctuations change drug ingestion.MethodsFemale C57BL/6 mice at two months old, were fed for eight weeks with a purified AIN93M diet, or a high-fat high-sucrose diet (HFHS). TEL 5 mg/Kg/day was administered ad libitum to mice in the drinking water during three weeks concomitant with diets, summing 11 weeks of diet feeding.ResultsUV spectrophotometry could detect TEL at the wavelength of 300 nm, and it remained stable in mice drinking water for seven days, at the concentration expected. Mice gain weight after eight weeks on high-fat high-sucrose diet feeding, and TEL 5 mg/kg/day in the drinking water for three weeks reduced it. TEL did not change water intake. Not adjusting TEL concentration weekly would lead to a higher intake of TEL by mice.DiscussionWe demonstrated that body mass and water intake fluctuations significantly change the amount of drug that the animal receive, and it would add a bias to the experiment. TEL remains stable for at least seven days in wrapped mice water bottles in the animal care facility, and UV spectrophotometry proved to be a simple and low-cost method to detect TEL in mice drinking water.
Huntingtin confers fitness but is not embryonically essential in zebrafish development
Authors: Sidik Harwin , Ang Christy J. , Pouladi Mahmoud A. 
Published: April 2019

AbstractAttempts to constitutively knockout HTT in rodents resulted in embryonic lethality, curtailing efforts to study HTT function later in development. Here we show that HTT is dispensable for early zebrafish development, contrasting published zebrafish morpholino experiment results. Homozygous HTT knockouts were embryonically viable and appeared developmentally normal through juvenile stages. Comparison of adult fish revealed significant reduction in body size and fitness in knockouts compared to hemizygotes and wildtype fish, indicating an important role for wildtype HTT in postnatal development. Our zebrafish model provides an opportunity to examine the function of wildtype HTT later in development.
Raw wastewater irrigation for urban agriculture in Africa increases the diversity of transferable antibiotic resistances genes in soil, including those encoding ESBLs
Authors: Bougnom B. P. , Thiele-Bruhn S. , Ricci V. , Zongo C. , Piddock L.J.V 
Published: April 2019

AbstractA metagenomic study was conducted to investigate the impact of raw wastewater use for irrigation in urban agriculture on the development of bacterial resistance in soil. Soil samples were collected in two African countries, from three different cities (each with irrigated and non-irrigated plots). Basic physical and chemical analysis were conducted, and the presence of selected antibiotic residues was assessed. Microbial DNA was extracted, quantified and sequenced. Microbial population structure and function, presence of horizontally transferable antibiotic resistance genes andEnterobacteriaceaeplasmids replicons were analysed using bioinformatics. The relative prevalence ofProteobacteriaandBacteroidetesand sequence reads coding for microbial adaptation and growth were higher in irrigated fields; 33 and 26 transferable ARGs were found in irrigated and non-irrigated fields sequence reads, respectively. Extended spectrum β-lactam genes identified in irrigated fields includedblaCARB-3,blaOXA-347,blaOXA-5 andblaRm3. Concentration of sulfamethoxazole, ciprofloxacin and enrofloxacin in soils influenced the selection of antibiotic resistance genes encoding resistance against amphenicol, β-lactams, and tetracyclines. TenEnterobacteriaceaeplasmid amplicon groups were identified in the fields, five were common to both, two (IncW and IncP1) and three (IncY, IncFIB and IncFIA) were found in irrigated and non-irrigated fields, respectively.In conclusion, wastewater irrigation affected both soil microbial diversity and functions. Irrigated fields have more diverse transferable antibiotic resistance genes, including ESBL genes that encode resistance to β-lactams antibiotics, except cephamycins and carbapenems. Even more, critical concentrations of antibiotic residues select for multiple and cross resistance. The findings from African cities show that wastewater irrigation in urban agriculture presents a serious public health risk for farmworkers and consumers by spread of bacterial resistance.
Re-weighting of Sound Localization Cues by Audiovisual Training
Authors: Kumpik Daniel P. , Campbell Connor , Schnupp Jan W.H. , King Andrew J 
Published: April 2019

AbstractSound localization requires the integration in the brain of auditory spatial cues generated by interactions with the external ears, head and body. Perceptual learning studies have shown that the relative weighting of these cues can change in a context-dependent fashion if their relative reliability is altered. One factor that may influence this process is vision, which tends to dominate localization judgments when both modalities are present and induces a recalibration of auditory space if they become misaligned. It is not known, however, whether vision can alter the weighting of individual auditory localization cues. Using non-individualized head-related transfer functions, we measured changes in subjects’ sound localization biases and binaural localization cue weights after ~55 minutes of training on an audiovisual spatial oddball task. Four different configurations of spatial congruence between visual and auditory cues (interaural time differences (ITDs) and frequency-dependent interaural level differences (interaural level spectra, ILS) were used. When visual cues were spatially congruent with both auditory spatial cues, we observed an improvement in sound localization, as shown by a reduction in the variance of subjects’ localization biases, which was accompanied by an up-weighting of the more salient ILS cue. However, if the position of either one of the auditory cues was randomized during training, no overall improvement in sound localization occurred. Nevertheless, the spatial gain of whichever cue was matched with vision increased, with different effects observed on the gain for the randomized cue depending on whether ITDs or ILS were matched with vision. As a result, we observed a similar up-weighting in ILS when this cue alone was matched with vision, but no overall change in binaural cue weighting when ITDs corresponded to the visual cues and ILS were randomized. Consistently misaligning both cues with vision produced the ventriloquism aftereffect, i.e., a corresponding shift in auditory localization bias, without affecting the variability of the subjects’ sound localization judgments, and no overall change in binaural cue weighting. These data show that visual contextual information can invoke a reweighting of auditory localization cues, although concomitant improvements in sound localization are only likely to accompany training with fully congruent audiovisual information.
A neuroanatomically grounded optimal control model of the compensatory eye movement system
Authors: Holland P.J. , Sibindi T.M. , Ginzburg M. , Das S. , Arkesteijn K. , Frens M.A. , Donchin O. 
Published: April 2019

AbstractWe present a working model of the compensatory eye movement system. We challenge the model with a data set of eye movements in mice (n=34) recorded in 4 different sinusoidal stimulus conditions with 36 different combinations of frequency (0.1-3.2 Hz) and amplitude (0.5-8°) in each condition. The conditions included vestibular stimulation in the dark (vestibular-ocular reflex, VOR), optokinetic stimulation (optokinetic reflex, OKR), and two combined visual/vestibular conditions (the visual-vestibular ocular reflex, vVOR, and visual suppression of the VOR, sVOR). The model successfully reproduced the eye movements in all conditions, except for minor failures to predict phase when gain was very low. Most importantly, it could explain the non-linear summation of VOR and OKR when the two reflexes are activated simultaneously during vVOR stimulation. In addition to our own data, we also reproduced the behavior of the compensatory eye movement system found in the existing literature. These include its response to sum-of-sines stimuli, its response after lesions of the nucleus prepositus hypoglossi or the flocculus, characteristics of VOR adaptation, and characteristics of drift in the dark. Our model is based on ideas of state prediction and forward modeling that have been widely used in the study of motor control. However, it represents one of the first quantitative efforts to simulate the full range of behaviors of a specific system. The model has two separate processing loops, one for vestibular stimulation and one for visual stimulation. Importantly, state prediction in the visual processing loop depends on a forward model of residual retinal slip after vestibular processing. In addition, we hypothesize that adaptation in the system is primarily adaptation of this model. In other words, VOR adaptation happens primarily in the OKR loop.