bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo and animal models of the human gut microbiome.
Authors: Goodman A. L.
Published: May 2014

This chapter describes current applications of in vivo animal models in studies related to the human gut microbiome, specifically those in the distal gut. These applications range from studying the biology of single host-associated microbial species to examining complete human communities containing hundreds of species transplanted into model hosts.
The gut microbiota in health and disease.
Authors: Ventura M. , Turroni F. , Strati F. , Sinderen D. van
Published: May 2014

This chapter reviews the important role of the gut microbial flora in the healthy state, as well as relevant alterations in their composition during various disease states (i.e., autoimmune diseases, inflammatory bowel diseases, allergies, colorectal cancer).
Next-generation sequencing methods to investigate the human microbiome.
Authors: Xiao Liang Xiao Liang , Qin JunJie Qin JunJie , Shen DongQian Shen DongQian , Jiang ChenMing Jiang ChenMing , Chen WanTing Chen WanTing , Liu Chuan Liu Chuan , Wang Jun Wang Jun
Published: May 2014

This chapter discusses current applications of three sequencing strategies (i.e., 16S rRNA gene sequencing, shotgun sequencing, transcriptome sequencing) in human microbiome research studies, highlighting their major intrinsic advantages and drawbacks.
Metabonomics for understanding gut microbiome and host metabolic interplay.
Authors: Li J. V. , Holmes E.
Published: May 2014

This chapter describes important metabolic profiling methods used in metabonomic studies, including nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and multivariate statistical analysis (chemometrics). Current applications of these methodologies are also discussed.
Peace and Conflict Impact Assessment of the Palestinian–Israeli Water Situation
Authors: Haddad Marwan
Published: May 2014

This paper examines and discusses the prolonged Palestinian–Israeli water conflict, taking into consideration recent formal and informal water negotiations and emphasising the future of water-based peacebuilding between the two sides. Sharing experience from the author's own water-related people-to-people work and in formal peace processes, it concludes by arguing that such efforts contribute to peacebuilding by closing the gaps in conflict-related understandings. It also argues the merits of developing and creating a Palestinian–Israeli Joint Water Authority (JWA). In particular, it proposes that such a joint institution should (1) minimise yesterday's ideology and politics, developing a future-oriented lens of practice, (2) develop and practise interdependency, and (3) create a context for the continued production of full equality and partnership rooted in international law and recognised practices. A five-element structure is proposed as guidance for future Palestinian-Israeli water-related peacebuilding.
Fellini's 8 ½ and Jung: narcissism and creativity in midlife
Authors: Fredericksen Don
Published: May 2014

Fellini's 8½, released in 1963, concerns a film director who has a midlife creative block. It is here viewed within the context of Fellini's discovery of Jung's writing and Jungian analysis in 1960. In Jung he found the mirroring he had not found in his childhood, or from the Catholic Church, or from the legacy of Italian neo-realist film. The film gives expression to the mixed results of Fellini's creative use of his discovery of Jung.
One or Two Gentle Remarks about Hans Halvorson’s Critique of the Semantic View
Authors: van Fraassen Bas C.
Published: May 2014

In recent papers Hans Halvorson has offered a critique of the semantic view of theories, showing that theories may be the same although the corresponding sets of models are different and, conversely, that theories may be different although the corresponding sets of models are the same. This critique will be assessed, first, as it pertains to issues concerning scientific models in the empirical sciences and, second, independent of any concern with empirical science.
Neuroeconomics and Confirmation Theory
Authors: Clarke Christopher
Published: May 2014

Neuroeconomics is a research program founded on the thesis that cognitive and neurobiological data constitute evidence for answering economic questions. I employ confirmation theory in order to reject arguments both for and against neuroeconomics. I also emphasize that some arguments for neuroeconomics will not convince the skeptics because these arguments make a contentious assumption: economics aims for predictions and deep explanations of choices in general. I then argue for neuroeconomics by appealing to a much more restrictive (and thereby skeptic-friendly) characterization of the aims of economics.
Reflections on equicontinuity
Authors: Auslander Joseph , Greschonig Gernot , Nagar Anima
Published: May 2014

We study different conditions which turn out to be equivalent to equicontinuity for a transitive compact Hausdorff flow with a general group action. Among them are a notion of “regional” equicontinuity, also known as the “Furstenberg” condition, and the condition that every point of the phase space is almost automorphic. Then we study relations on the phase space arising from dynamical properties, among them the regionally proximal relation and two relations introduced by Veech. We generalize Veech’s results for minimal actions of non-Abelian groups preserving a probability measure with respect to the regionally proximal relation. We provide proofs in the framework of dynamical systems rather than harmonic analysis as given by Veech.
Seventeenth-century ‘treasure’ found in Royal Society archives: The
Ludus helmontii
and the stone disease
Authors: Alfonso-Goldfarb Ana Maria , Ferraz Márcia Helena Mendes , Rattansi Piyo M.
Published: May 2014

Our archival researches at the Royal Society reveal that a small envelope attached to a 1675 letter from an Antwerp apothecary, A. Boutens, contained a sample of the ‘
Ludus
’ prepared as a remedy for the ‘stone disease’ then sweeping through Europe, which was first announced in J. B. van Helmont's
De lithiasi
(1644). After examining the fascination with the medical use of the
Ludus
(which required the ‘alkahest’ for its preparation) and the tenacious efforts to procure it, we trace the
fortunae
of two other
ludi
in England, brought to and offered by Francis Mercurius van Helmont during his English sojourn. Both eventually found their way to the geologist John Woodward, one of them through Sir Isaac Newton. Finally we show how the allure of the
Ludus helmontii
vanished, with transformations in mineral analysis and reclassifications from Woodward to John Hill.
Developments in optics and performance at BL13-XALOC, the macromolecular crystallography beamline at the Alba Synchrotron
Authors: Juanhuix Jordi , Gil-Ortiz Fernando , Cuní Guifré , Colldelram Carles , Nicolás Josep , Lidón Julio , Boter Eva , Ruget Claude , Ferrer Salvador , Benach Jordi
Published: May 2014

BL13-XALOC is currently the only macromolecular crystallography beamline at the 3 GeV ALBA synchrotron near Barcelona, Spain. The optics design is based on an in-vacuum undulator, a Si(111) channel-cut crystal monochromator and a pair of KB mirrors. It allows three main operation modes: a focused configuration, where both mirrors can focus the beam at the sample position to 52 µm × 5.5 µm FWHM (H × V); a defocused configuration that can match the size of the beam to the dimensions of the crystals or to focus the beam at the detector; and an unfocused configuration, where one or both mirrors are removed from the photon beam path. To achieve a uniform defocused beam, the slope errors of the mirrors were reduced down to 55 nrad RMS by employing a novel method that has been developed at the ALBA high-accuracy metrology laboratory. Thorough commissioning with X-ray beam and user operation has demonstrated an excellent energy and spatial stability of the beamline. The end-station includes a high-accuracy single-axis diffractometer, a removable mini-kappa stage, an automated sample-mounting robot and a photon-counting detector that allows shutterless operation. The positioning tables of the diffractometer and the detector are based on a novel and highly stable design. This equipment, together with the operation flexibility of the beamline, allows a large variety of types of crystals to be tackled, from medium-sized crystals with large unit-cell parameters to microcrystals. Several examples of data collections measured during beamline commissioning are described. The beamline started user operation on 18 July 2012.
Plant neighbours rather than soil biota determine impact of an alien plant invader
Authors: Sun Yan , Müller‐Schärer Heinz , Schaffner Urs
Published: May 2014

Various factors have been shown contributing to the ecosystem impact of invasive alien plants, but their relative importance remains unclear. We focused on the effects of neighbouring plant community and soil biota as these biotic factors have been repeatedly put forward to explain invasion success (e.g. as components of the novel weapons and of the biotic release hypothesis).

To assess their relative importance in explaining the high impact of Centaurea stoebe during the invasion of new sites in the introduced range, we conducted a greenhouse experiment with both European (EU) and North American (NA) tetraploid C. stoebe competing with/without EU vs. NA neighbouring community and with the two neighbouring communities growing without C. stoebe. Plants were grown in sterilized commercial soil inoculated with naïve soil (from rhizosphere of plants other than C. stoebe) originating either from the home EU or the introduced NA range and half of which was sterilized to remove soil biota.

In the competition pots, relative competitive ability (difference between the relative growth rates of C. stoebe and neighbouring community) and impact level (biomass of the neighbouring community relative to that in non‐competition pots) of C. stoebe was significantly higher when grown with the NA than with the EU neighbouring community, although growth rates of EU and NA neighbouring communities did not differ in the non‐competition pots. Both soil origin and C. stoebe origin had no effect on these processes. Soil sterilization increased growth of both C. stoebe and neighbouring communities, but had only a moderate effect on impact level and type, and no effect on the relative competitive ability of C. stoebe.

These results suggest that during the colonization of new sites in North American grasslands, the impact of C. stoebe is strongly driven by reduced competitive ability of NA neighbours compared with EU neighbours, while altered biotic soil conditions in the introduced range and post‐introduction evolutionary changes in the invader are of less importance. This differential impact appears to be due to inherently different mechanisms underlying the competitive interactions between EU and NA neighbouring communities when grown with C. stoebe.
REVIEW: The evolving linkage between conservation science and practice atTheNatureConservancy
Authors: Kareiva Peter , Groves Craig , Marvier Michelle
Published: May 2014

TheNatureConservancy (TNC) was founded by ecologists as aUnitedStates land trust to purchase parcels of habitat for the purpose of scientific study. It has evolved into a global organization working in 35 countries ‘to conserve the lands and waters on which all life depends’.TNCis now the world's largest conservation non‐governmental organization (NGO), an early adopter of advances in ecological theory and a producer of new science as a result of practising conservation.

TheNatureConservancy's initial scientific innovation was the use of distributional data for rare species and ecological communities to systematically target lands for conservation. This innovation later evolved into a more rigorous approach known as ‘Conservation byDesign’ that contained elements of systematic conservation planning, strategic planning and monitoring and evaluation.

The next scientific transition atTNCwas a move to landscape‐scale projects, motivated by ideas from landscape ecology. Because the scale at which land could be set aside in areas untouched by humans fell far short of the spatial scale demanded by conservation,TNCbecame involved with best management practices for forestry, grazing, agriculture, hydropower and other land uses.

A third scientific innovation atTNCcame with the pursuit of multiobjective planning that accounts for economic and resource needs in the same plans that seek to protect biodiversity.

TheMillenniumEcosystemAssessment promptedTNCto become increasingly concerned with ecosystem services and the material risk to people posed by ecosystem deterioration.

Finally, because conservation depends heavily upon negotiation,TNChas recently recruited social scientists, economists and communication experts. One aspect still missing, however, is a solid scientific understanding of thresholds that should be averted.

Synthesis and applications. Over its 60‐plus year history, scientific advances have informedTheNatureConservancy (TNC)'s actions and strategies, and in turn the evolving practice of conservation has altered the type of science sought byTNCin order to maximize its conservation effectiveness.
Windows of opportunity for germination of riparian species after restoring water level fluctuations: a field experiment with controlled seed banks
Authors: Sarneel Judith M. , Janssen Roel H. , Rip Winnie J. , Bender Irene M. A. , Bakker Elisabeth S.
Published: May 2014

Restoration activities aiming at increasing vegetation diversity often try to stimulate both dispersal and germination. In wetlands, dispersal and germination are coupled as water and water level fluctuations (WLF) simultaneously influence seed transport and germination conditions (soil moisture). Water regime shifts have been shown to affect vegetation composition. However, the interactions between WLF, dispersal and subsequent germination as drivers of such changes are still poorly understood, especially within the complexity of a field situation.

We tested the effect of soil moisture on ten riparian species in the greenhouse and sowed these species on 135 field locations in nine wetlands with recently restored WLF. We used quantile regressions to test the effects of WLF on the window of opportunity for germination from sown seeds and other seeds naturally dispersed to our plots, as well as on community diversity.

Soil moisture significantly affected germination both in the greenhouse and in the field. In the complexity of a field situation, a flooding depth just below the soil level, an intermediate flooding duration and a high flooding frequency provided the best opportunities for maximal germination. This was because these conditions enhanced germination from the seed bank as well as increasing germination from dispersed seeds. Seedling diversity showed identical patterns.

Other known (i.e., light conditions) and unknown factors played a role as we found low and variable germination, even under optimal conditions. We found evidence that WLF can affect vegetation zonation as flooded seedling communities contained more species with high moisture affinity.

Synthesis and applications. Water level fluctuations provide clear windows of opportunity for germination both from the seed bank and from dispersed seeds. Water regime changes are therefore likely to strongly affect recruitment opportunities and subsequent community assembly in riparian ecosystems, for instance through climate change or management. Water level fluctuations can be used as management tool to stimulate plant recruitment and seedling diversity in riparian wetlands.
Methods for Assessing Patient–Clinician Communication about Depression in Primary Care: What You See Depends on How You Look
Authors: Henry Stephen G. , Feng Bo , Franks Peter , Bell Robert A. , Tancredi Daniel J. , Gottfeld Dustin , Kravitz Richard L.
Published: May 2014

Objective

To advance research on depression communication and treatment by comparing assessments of communication about depression from patient report, clinician report, and chart review to assessments from transcripts.

Data

One hundred sixty‐four primary care visits from seven health care systems (2010–2011).

Study Design

Presence or absence of discussion about depressive symptoms, treatment recommendations, and follow‐up was measured using patient and clinician postvisit questionnaires, chart review, and coding of audio transcripts. Sensitivity and specificity of indirect measures compared to transcripts were calculated.

Principal Findings

Patient report was sensitive for mood (83 percent) and sleep (83 percent) but not suicide (55 percent). Patient report was specific for suicide (86 percent) but not for other symptoms (44–75 percent). Clinician report was sensitive for all symptoms (83–98 percent) and specific for sleep, memory, and suicide (80–87 percent), but not for other symptoms (45–48 percent). Chart review was not sensitive for symptoms (50–73 percent), but it was specific for sleep, memory, and suicide (88–96 percent). All indirect measures had low sensitivity for treatment recommendations (patient report: 24–42 percent, clinician report 38–50 percent, chart review 49–67 percent) but high specificity (89–96 percent). For definite follow‐up plans, all three indirect measures were sensitive (82–96 percent) but not specific (40–57 percent).

Conclusions

Clinician report and chart review generally had the most favorable sensitivity and specificity for measuring discussion of depressive symptoms and treatment recommendations, respectively.
Expanding Coverage to Low‐Income Childless Adults in Massachusetts: Implications for National Health Reform
Authors: Long Sharon K. , Dahlen Heather
Published: May 2014

Objective

To draw on the experiences under Massachusetts's 2006 reform, the template for the Affordable Care Act (ACA), to provide insights into the potential impacts of the ACA Medicaid expansion for low‐income childless adults in other states.

Data Sources/Study Setting

The study takes advantage of the natural experiment in Massachusetts and combined data from two surveys—the Massachusetts Health Reform Survey (MHRS) and the National Health Interview Survey (NHIS)—to estimate the impacts of reform on low‐income adults.

Study Design

Difference‐in‐differences models of the impacts of health reform, using propensity‐score reweighting to improve the match between Massachusetts and the comparison states.

Data Collection/Extraction Methods

Data for low‐income adults are obtained by combining data from the MHRS and the NHIS, where the MHRS provides a relatively large Massachusetts sample and the NHIS provides data for samples in other states to support the difference‐in‐differences model. Supplemental data on county economic and health care market characteristics are obtained from the Area Health Resource File.

Principal Findings

There are strong increases in coverage and access to health care for low‐income adults under health reform in Massachusetts, with the greatest gains observed for childless adults, who were not eligible for public coverage prior to reform.

Conclusions

In the states that implement the Medicaid provisions of the ACA, we would expect to see large increases in coverage rates and commensurate gains in access to care for low‐income childless adults. Linking state and federal surveys offers a strategy for leveraging the value of state‐specific survey data for stronger policy evaluations.
Forensic Analysis of MTBE Contamination Using Basic Hydrogeologic Concepts
Authors: Boving Thomas
Published: May 2014

Contamination of groundwater with petroleum hydrocarbons and additives, such as methyl tert‐butyl ether (MTBE), is often linked to the leaking product distribution system of gas stations. In very few cases is it know if and when a leak occurred and how much product was released to the environment. In the absence of direct evidence, a careful analysis of the available data, such as contaminant breakthrough at receptor wells or discrepancies in the product inventory data, may provide evidence about the nature of the release, its timing and magnitude. Using a MTBE contamination site in the formerly glaciated New England region as an example, two possible release scenarios (slow, long‐term release vs. spill) were examined. Of the two scenarios, the slow release could be ruled out as the sole source even though there was no direct evidence for a spill. The analysis of hydraulic test results together with chemical data further permitted to estimate when such an undocumented spill might have occurred. Analyses of the data also allowed these results to be compared to that of a prior transport and fate modeling study. Good agreement and consistency for contaminant travel times was confirmed. This forensic analysis demonstrates that applying basic hydrogeologic principles can aide in the reconstruction of contamination events while providing more readily understandable and defendable evidence relative to complex models. Conceptually, the approach described herein is transferable to other sites with similar hydrogeologies.
Use of genotyping by sequencing data to develop a high‐throughput and multifunctional SNP panel for conservation applications in Pacific lamprey
Authors: Hess Jon E. , Campbell Nathan R. , Docker Margaret F. , Baker Cyndi , Jackson Aaron , Lampman Ralph , McIlraith Brian , Moser Mary L. , Statler David P. , Young William P. , Wildbill Andrew J. , Narum Shawn R.
Published: May 2014

Next‐generation sequencing data can be mined for highly informative single nucleotide polymorphisms (SNPs) to develop high‐throughput genomic assays for nonmodel organisms. However, choosing a set of SNPs to address a variety of objectives can be difficult because SNPs are often not equally informative. We developed an optimal combination of 96 high‐throughput SNP assays from a total of 4439 SNPs identified in a previous study of Pacific lamprey (Entosphenus tridentatus) and used them to address four disparate objectives: parentage analysis, species identification and characterization of neutral and adaptive variation. Nine of these SNPs are FST outliers, and five of these outliers are localized within genes and significantly associated with geography, run‐timing and dwarf life history. Two of the 96 SNPs were diagnostic for two other lamprey species that were morphologically indistinguishable at early larval stages and were sympatric in the Pacific Northwest. The majority (85) of SNPs in the panel were highly informative for parentage analysis, that is, putatively neutral with high minor allele frequency across the species’ range. Results from three case studies are presented to demonstrate the broad utility of this panel of SNP markers in this species. As Pacific lamprey populations are undergoing rapid decline, these SNPs provide an important resource to address critical uncertainties associated with the conservation and recovery of this imperiled species.
Low incidence of bacteriuria with outpatient flexible cystoscopy
Authors: Lo Tsia‐Shu , Khanuengkitkong Siwatchaya , Tan Yiap Loong , Dass Anil Krishna , Wu Pei‐Ying , Al‐Kharabsheh Ahlam Mahmoud
Published: May 2014

Aim

To evaluate the incidence of bacteriuria after outpatient diagnostic flexible cystoscopy utilising sterile catheter urine collection technique in women.

Materials and Methods

This is a prospective observational study on 78 women who had outpatient flexible cystoscopy for various indications between March and December 2011. Urine for culture was collected by transurethral catheterisation three to five days before cystoscopy, and a second urine sample was collected five to seven days after the procedure. Antibiotic prophylaxis was not administered. Significant bacteriuria was defined as 102 cfu/mL or more of a single organism cultured.

Results

Five (6.4%) had significant bacteriuria and were asymptomatic. The most common organism cultured was Escherichia coli in 4 (80%) of the infected women. No other cystoscopic complication was observed. The mean age was 54.7 years (range 27–80), mean parity was 2.8 (range 0–7). In the study group, 54 (69.2%) women were postmenopausal, 9 (11.5%) had diabetes mellitus, 42 (53.8%) had pelvic organ prolapse and 22 (28.2%) had a prior hysterectomy. Most common indications for cystoscopy were hematuria and recurrent UTI, 48 (61.5%) and 22 (28.2%) women respectively. The cystoscopic findings were normal in 59 (75.6%) women. The procedure was completed within five minutes in all participants.

Conclusion

The incidence of bacteriuria following outpatient flexible cystoscopy is low.
A systematic review of peri‐operative melatonin
Authors: Andersen L. P. H. , Werner M. U. , Rosenberg J. , Gögenur I.
Published: May 2014

We systematically reviewed randomised controlled trials of peri‐operative melatonin. We included 24 studies of 1794 participants that reported eight peri‐operative outcomes: anxiety; analgesia; sleep quality; oxidative stress; emergence behaviour; anaesthetic requirements; steal induction; and safety. Compared with placebo, melatonin reduced the standardised mean difference (95% CI) pre‐operative anxiety score by 0.88 (0.44–1.33) and postoperative pain score by 1.06 (0.23–1.88). The magnitude of effect was unreliable due to substantial statistical heterogeneity, with I2 87% and 94%, respectively. Qualitative reviews suggested the melatonin improved sleep quality and emergence behaviour, and might be capable of reducing oxidative stress and anaesthetic requirements.
Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity
Authors: Sotozono Chie , Inatomi Tsutomu , Nakamura Takahiro , Koizumi Noriko , Yokoi Norihiko , Ueta Mayumi , Matsuyama Kotone , Kaneda Hideaki , Fukushima Masanori , Kinoshita Shigeru
Published: May 2014

Purpose

To assess the clinical efficacy of cultivated oral mucosal epithelial transplantation (COMET) for the treatment of persistent epithelial defect (PED).

Methods

We treated 10 eyes of nine patients with PED (Stevens–Johnson syndrome: three eyes; thermal/chemical injury: five eyes; ocular cicatricial pemphigoid: two eyes) with COMET at Kyoto Prefectural University of Medicine, Kyoto, Japan from 2002 to 2008.

Results

Preoperatively, PED existed on over more than 50% of the corneal surface in seven eyes. Severe ocular surface inflammation with fibrovascular tissue surrounded the PED in all 10 eyes. At 24‐weeks postoperative, PED had improved in all cases except 1 in which the patient was unable to return to the hospital (95% CI, 55.5–99.7; Wilcoxon signed‐rank test, p = 0.0078). The preoperative median of logarithmic minimum angle of resolution was 1.85 (range 0.15–2.70), and 1.85, 1.85, and 1.52 at the 4th, 12th, and 24th postoperative week, respectively. The mean total preoperative ocular surface grading score was 7.0 (range 4–17). At 4 and 12 weeks postoperative, the total ocular surface grading score had improved significantly (p = 0.0020, p = 0.0078), and at 24 weeks postoperative, it was 3.0 (range 2–12, p = 0.0234). During the follow‐up period (median 23.3 months, range 5.6–39.7 months), no recurrence of PED was observed in any eye, and long‐term ocular surface stability was obtained.

Conclusion

COMET enabled complete epithelialization of PED and stabilization of the ocular surface in patients with severe ocular surface disease, thus preventing end‐stage cicatrization and vision loss at a later stage.
Femtosecond‐laser assisted cataract surgery: a review
Authors: Abouzeid Hana , Ferrini Walter
Published: May 2014

Introduced in 2008, the femtosecond laser is a promising new technological advance which plays an ever increasing role in cataract surgery where it automates the three main surgical steps: corneal incision, capsulotomy and lens fragmentation. The proven advantages over manual surgery are: a better quality of incision with reduced induced astigmatism; increased reliability and reproducibility of the capsulotomy with increased stability of the implanted lens; a reduction in the use of ultrasound. Regarding refractive results or safety, however, no prospective randomized study to date has shown significant superiority compared with standard manual technique. The significant extra cost generated by this laser, undertaken by the patient, is a limiting factor for both its use and study. This review outlines the potential benefits of femtosecond‐laser‐assisted cataract surgery due to the automation of key steps and the safety of this new technology.
Metabolic syndrome as a risk factor in normal‐tension glaucoma
Authors: Kim Mijin , Jeoung Jin Wook , Park Ki Ho , Oh Won Hyuck , Choi Hyuk Jin , Kim Dong Myung
Published: May 2014

Purpose

To determine whether normal‐tension glaucoma (NTG) is associated with metabolic syndrome and to evaluate which components of metabolic syndrome are related to NTG.

Methods

This study included 18240 participants who underwent health check‐ups including fundus photography and intraocular pressure measurements. For NTG diagnosis, all participants with findings suggestive of glaucoma completed a further glaucoma evaluation, including applanation tonometry, gonioscopy and standard automated perimetry. The National Cholesterol Education Program Adult Treatment Panel III guideline was used to characterize metabolic syndrome.

Results

Of the 18240 participants, 3635 (19.9%) had metabolic syndrome and 300 (1.6%) were diagnosed with NTG. The prevalence of NTG was 1.5% in subjects without metabolic syndrome and 2.1% in subjects with metabolic syndrome. The presence of metabolic syndrome was not significantly associated with NTG (p = 0.067). There were significant associations of NTG with hypertension and impaired glucose tolerance (IGT) among the individual components of metabolic syndrome (OR, 1.53; 95% CI, 1.20–1.94; p = 0.001 and OR, 1.47; 95% CI, 1.12–1.94; p = 0.006). NTG was positively associated with the number of metabolic syndrome components (OR, 1.10; p = 0.040). Multivariable analysis showed the prevalence of NTG to be significantly higher in participants aged between 50 and 70 years relative to those aged 40 to 50 years, male gender, participants with higher baseline intraocular pressure, hypertension and IGT.

Conclusions

Of the metabolic syndrome components, hypertension and IGT contributed to an increased risk of NTG. These findings suggest that metabolic syndrome components may play a role in the pathogenesis of NTG.
Incidence and clinical characteristics of fungal keratitis in a Danish population from 2000 to 2013
Authors: Nielsen Stine E. , Nielsen Esben , Julian Hanne Olsen , Lindegaard Jens , Højgaard Klavs , Ivarsen Anders , Hjortdal Jesper , Heegaard Steffen
Published: May 2014

Purpose

Fungal keratitis is a severe sight‐threatening condition. The aim of this study was to investigate the incidence and clinical characteristics of fungal keratitis patients living in a temperate climate.

Methods

By reviewing medical records from 2000 to July 2013, patients with fungal keratitis were identified. Risk factors, clinical signs and outcome were registered.

Results

Twenty‐five patients were identified: 52% with Candida, 20% with Fusarium, 16% with Aspergillus and 12% with mixed filamentous fungi. A minimum incidence of fungal keratitis of 0.6 cases per million per year was estimated. Prior topical steroid treatment was commonly found in our cases (44%). Trauma including contact lens wear was associated with infection with filamentous fungi, whereas in patients with Candida infection, ocular surface disease was a prominent feature. Median time from onset of symptoms to diagnosis was 24 days. Only a few patients exhibited classical clinical features such as endothelial plaques (28%), satellite lesions (24%) and feathery edges (16%). The final visual outcome was poor with an average best‐corrected logMAR of (mean, 95% CI) 0.70 (0.4–1.0). A total of 52% were treated with corneal transplantation. Patients with Candida infections had a significantly worse visual outcome.

Conclusion

We found that patients with fungal keratitis had a poor visual outcome. However, knowledge of risk factors and clinical signs leading to early treatment can improve the prognosis.
The Evaluation of Prophylactic Efficacy of Newly Developed Reversible Inhibitors of Acetylcholinesterase in Soman‐Poisoned Mice – A Comparison with Commonly Used Pyridostigmine
Authors: Kassa Jiri , Korabecny Jan , Sepsova Vendula , Tumova Martina
Published: May 2014

The ability of four newly developed reversible inhibitors of acetylcholinesterase (PC‐37, PC‐48, JaKo 39, JaKo 40) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman‐poisoned mice was evaluated and compared. No reversible inhibitor of acetylcholinesterase studied was able to decrease the LD50 value of soman in mice. Thus, the pharmacological pre‐treatment with pyridostigmine or newly synthesized inhibitors of acetylcholinesterase was not able to significantly protect mice against soman‐induced lethal acute toxicity. In addition, neither pyridostigmine nor new reversible inhibitors of acetylcholinesterase was able to increase the efficacy of antidotal treatment (the oxime HI‐6 in combination with atropine) of soman‐poisoned mice. These findings demonstrate that pharmacological pre‐treatment of soman‐poisoned mice with tested reversible inhibitors of acetylcholinesterase is not promising.
Silencing histone deacetylase 2 using small hairpin RNA induces regression of fibrotic plaque in a rat model of Peyronie's disease
Authors: Kwon Ki‐Dong , Choi Min Ji , Park Jin‐Mi , Song Kang‐Moon , Kwon Mi‐Hye , Batbold Dulguun , Yin Guo Nan , Kim Woo Jean , Ryu Ji‐Kan , Suh Jun‐Kyu
Published: May 2014

Objectives

To examine the therapeutic effect of adenovirus encoding histone deacetylase 2 (HDAC2) small hairpin RNA (Ad‐HDAC2 shRNA) in a rat model of Peyronie's disease (PD) and to determine the mechanisms by which HDAC2 knockdown ameliorates fibrotic responses in primary fibroblasts derived from human PD plaque.

Materials and Methods

Rats were distributed into four groups (n = 6 per group): age‐matched controls without treatment; rats in which PD has been induced (PD rats) without treatment; PD rats receiving a single injection of control adenovirus encoding scrambled small hairpin RNA (Ad‐shRNA) (day 15; 1 × 108 pfu/0.1 mL phosphate‐buffered saline [PBS]); and PD rats receiving a single injection of Ad‐HDAC2 shRNA (day 15; 1 × 108 pfu/0.1 mL PBS) into the lesion. PD‐like plaque was induced by repeated intratunical injections of 100 μL each of human fibrin and thrombin solutions on days 0 and 5. On day 30, the penis was harvested for histological examination. Fibroblasts isolated from human PD plaque were pretreated with HDAC2 small interfering (si)RNA (100 pmoL) and then stimulated with transforming growth factor (TGF)‐β1 (10 ng/mL) to determine hydroxyproline levels, procollagen mRNA, apoptosis and protein expression of poly(ADP‐ribose) polymerase 1 (PARP1) and cyclin D1.

Results

We observed that Ad‐HDAC2 shRNA decreased inflammatory cell infiltration, reduced transnuclear expression of phospho‐Smad3 and regressed fibrotic plaque of the tunica albuginea in PD rats in vivo. siRNA‐mediated silencing of HDAC2 significantly decreased the TGF‐β1‐induced transdifferentiation of fibroblasts into myofibroblasts and collagen production, and induced apoptosis by downregulating the expression of PARP1, and decreased the expression of cyclin D1 (a positive cell‐cycle regulator) in primary cultured fibroblasts derived from human PD plaque in vitro.

Conclusion

Specific inhibition of HDAC2 with RNA interference may represent a novel targeted therapy for PD.
Coating doxorubicin‐loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1‐type immune responses
Authors: Kansal S , Tandon R , Verma A , Misra P , Choudhary A K , Verma R , Verma P R P , Dube A , Mishra P R
Published: May 2014

Background and Purpose

The aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate‐(SA) coated nanocapsule (NCs) loaded with doxorubicin (SA‐NCs‐DOX) against visceral leishmaniasis in comparison with nano‐emulsions containing doxorubicin (NE‐DOX).

Experimental Approach

NE‐DOX was prepared using low‐energy emulsification methods. Stepwise addition of protamine sulphate and SA in a layer‐by‐layer manner was used to form SA‐NCs‐DOX. SA‐NCs‐DOX, NE‐DOX and Free DOX were compared for their cytotoxicity against Leishmania donovani‐infected macrophages in vitro and generation of T‐cell responses in infected hamsters in vivo.

Key Results

Size and ζ potential of the NE‐DOX and SA‐NCs‐DOX formulations were 310 ± 2.1 nm and (−)32.6 ± 2.1 mV, 342 ± 4.1 nm and (−)29.3 ± 1.2 mV respectively. SA‐NCs‐DOX was better (1.5 times) taken up by J774A.1 macrophages compared with NE‐DOX. SA‐NCs ‐DOX showed greater efficacy than NE‐DOX against intramacrophagic amastigotes. SA‐NCs‐DOX treatment exhibited enhanced apoptotic efficiency than NE‐DOX and free DOX as evident by cell cycle analysis, decrease in mitochondrial membrane potential, ROS and NO production. T‐cell responses, when assessed through lymphoproliferative responses, NO production along with enhanced levels of iNOS, TNF‐α, IFN‐γ and IL‐12 were found to be up‐regulated after SA‐NCs‐DOX, compared with responses to NE‐DOX in vivo. Parasitic burden was decreased in Leishmania‐infected hamsters treated with SA‐NCs‐DOX, compared with NE‐DOX.

Conclusions and Implications

Our results provide insights into the development of an alternative approach to improved management of leishmaniasis through a combination of chemotherapy with stimulation of the innate immune system.
Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders
Authors: Bukalo Olena , Pinard Courtney R , Holmes Andrew
Published: May 2014

The burden of anxiety disorders is growing, but the efficacy of available anxiolytic treatments remains inadequate. Cognitive behavioural therapy for anxiety disorders focuses on identifying and modifying maladaptive patterns of thinking and behaving, and has a testable analogue in rodents in the form of fear extinction. A large preclinical literature has amassed in recent years describing the neural and molecular basis of fear extinction in rodents. In this review, we discuss how this work is being harnessed to foster translational research on anxiety disorders and facilitate the search for new anxiolytic treatments. We begin by summarizing the anatomical and functional connectivity of a medial prefrontal cortex (mPFC)–amygdala circuit that subserves fear extinction, including new insights from optogenetics. We then cover some of the approaches that have been taken to model impaired fear extinction and associated impairments with mPFC–amygdala dysfunction. The principal goal of the review is to evaluate evidence that various neurotransmitter and neuromodulator systems mediate fear extinction by modulating the mPFC–amygdala circuitry. To that end, we describe studies that have tested how fear extinction is impaired or facilitated by pharmacological manipulations of dopamine, noradrenaline, 5‐HT, GABA, glutamate, neuropeptides, endocannabinoids and various other systems, which either directly target the mPFC–amygdala circuit, or produce behavioural effects that are coincident with functional changes in the circuit. We conclude that there are good grounds to be optimistic that the progress in defining the molecular substrates of mPFC–amygdala circuit function can be effectively leveraged to identify plausible candidates for extinction‐promoting therapies for anxiety disorders.

Linked Articles

This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐20
Ulinastatin activates haem oxygenase 1 antioxidant pathway and attenuates allergic inflammation
Authors: Song Dongmei , Song Geng , Niu Yinghao , Song Wei , Wang Jiantao , Yu Lei , Yang Jianwang , Lv Xin , Steinberg Harry , Liu Shu Fang , Wang Baoshan
Published: May 2014

Background and Purpose

Ulinastatin (UTI), a serine protease inhibitor, was recently found to have an anti‐inflammatory action. However, the mechanisms mediating this anti‐inflammatory effect are not well understood. This study tested the hypothesis that UTI suppresses allergic inflammation by inducing the expression of haem oxygenase 1 (HO1).

Experimental Approach

Control mice and mice sensitized (on days 1, 9 and 14) and challenged (on days 21 to 27) with ovalbumin (OVA) were treated with UTI. The effects of UTI on basal expression of HO1 and that induced by OVA challenge were examined. The involvement of UTI‐induced HO1 expression in anti‐inflammatory and antioxidant effects of UTI was also evaluated.

Key Results

UTI markedly increased basal HO1 protein expression in lungs of control mice in a time‐ and dose‐dependent manner, and augmented HO1 protein expression induced by OVA. The up‐regulation of HO1 mediated by UTI in sensitized and OVA‐challenged mice was associated with reduced airway inflammation, alleviated tissue injury, reduced oxidant stress and enhanced antioxidant enzyme activities. Inhibition of HO1 activity using HO1 inhibitor, zinc protoporphyrin, attenuated inhibitory effects of UTI on inflammation and oxidant stress, and its stimulant effects on antioxidant enzyme activities. Mechanistic analysis showed that UTI increased nuclear translocation of nuclear factor erythroid 2‐related factor 2 (Nrf2), stimulated Nrf2 DNA binding activity and concomitantly up‐regulated HO1 mRNA expression.

Conclusions and Implications

UTI is a potent and naturally occurring inducer of HO1 expression. HO1 up‐regulation contributes significantly to the anti‐inflammatory and organ‐protective effects of UTI, which has important research and therapeutic implications.
Accuracy of a novel prototype dynamic computer‐assisted surgery system
Authors: Somogyi‐Ganss Eszter , Holmes Howard I. , Jokstad Asbjørn
Published: May 2014

Objectives

To implement and evaluate the accuracy of a prototype dynamic computer‐assisted surgery (CAS) system for implant osteotomy preparation and compare its accuracy vs. three commercial static CAS systems and the use of an acrylic stent.

Material and methods

Eight osteotomies were prepared in radiopaque partially edentulous mandible and maxilla typodonts. After cone‐beam CT acquisition, DICOM files were imported into a prototype dynamic, and three static CAS systems (NobelClinician, Simplant, and CoDiagnostiX). Implant placements were planned to replicate the existing osteotomies and respective guides were requisitioned, along with one laboratory‐made acrylic guide. The eight osteotomies per jaw were transferred to one typodont pair mounted in a manikin in a clinical setting and the process was repeated for four additional pairs. The 80 (two jaws × eight holes × five pairs) osteotomies were filled with radiopaque cement in‐between the testing series. Three clinicians experienced with the use of the static CAS softwares used in this study prepared each 400 (80 holes × five modalities) osteotomies. One clinician repeated the experiment twice, resulting in a total of 2000 (five clinicians × 400) osteotomies. The lateral, vertical, total, and angular deviations of the actual vs. the original osteotomies in the master typodonts were measured using stereo optical tracking cameras. Linear regression statistics using generalized estimating equations were used for comparisons between the five modalities and omnibus chi‐square tests applied to assess statistical significance of differences.

Results

The prototype dynamic CAS system was as accurate as other implant surgery planning and transfer modalities. The dynamic and static CAS systems provide superior accuracy vs. a laboratory‐made acrylic guide, except vertically. Both dynamic and static CAS systems show on average <2 mm and 5 degrees error. Large deviations between planned and actual osteotomies were occasionally observed, which needs to be considered in clinical practice.

Conclusions

The prototype dynamic CAS system was comparably accurate to static CAS systems.
Impact of chronic kidney disease on postoperative outcome following colorectal cancer surgery
Authors: Currie A. , Malietzis G. , Askari A. , Nachiappan S. , Swift P. , Jenkins J. T. , Faiz O. D. , Kennedy R. H.
Published: May 2014

Aim

Chronic kidney disease (CKD) is increasing in prevalence and is associated with cardiovascular events and mortality in asymptomatic and vascular surgery populations. This study aimed to determine the role of CKD in stratifying peri‐ and postoperative risk for colorectal cancer (CRC) patients with nonmetastatic disease undergoing elective curative resection.

Method

Patients diagnosed with nonmetastatic colorectal adenocarcinoma and undergoing surgical resection between 2006 and 2011 were identified from a prospectively collated database. Further information on survival and cause of death was gathered from a regional cancer registry. Estimated glomerular filtration rates were calculated using the Modification of Diet in Renal Disease (MDRD) equation. Kaplan–Meier survival curves were constructed for disease‐free and overall survival. Multivariate Cox regression models were used to determine the role of CKD after stratification by several clinicopathological factors.

Results

Seven‐hundred and eight colorectal resections were studied [median follow up: 45 (interquartile range, 21–65) months). Overall postoperative complications were similar, but patients with CKD were more likely to develop cardiovascular morbidity (P < 0.001) and 30‐day mortality [4.8% (six of 124) in the CKD group vs 2.1% (12/580) in the non‐CKD group]. Kaplan–Meier analysis revealed poorer overall survival for localized (Stage I–II; P = 0.019) and Stage III (P = 0.001) CRC in the CKD population. Multivariate Cox regression analysis identified CKD as an independent prognostic factor for noncancer death [hazard ratio (HR) = 1.82 (95% CI: 1.07–3.10); P = 0.027] but not for overall survival [HR = 1.21 (95% CI: 0.90–1.47); P = 0.116].

Conclusion

Patients with CKD may be more likely to develop cardiovascular complications following CRC resection and have an increased risk of a noncancer death. Future research should explore the interaction of CKD in competing mortality risks following CRC surgery.
Long‐term outcome of stenting as a bridge to surgery for acute left‐sided malignant colonic obstruction
Authors: Quereshy F. A. , Poon J. T. C. , Law W. L.
Published: May 2014

Aim

This study aimed to evaluate both the short‐ and long‐term outcomes associated with colonic stenting as a bridge to surgery in patients with obstructing adenocarcinoma of the colon.

Method

Patients with potentially curable acute left‐sided colonic obstruction treated with stenting as a bridge to surgery (n = 28) or with emergency surgical resection (n = 39) from January 1998 to December 2008 were identified from a prospectively maintained database. Short‐term data on postoperative mortality, morbidity, necessity of intensive care and length of hospital stay were compared. Overall survival and disease‐free survival were also analysed.

Results

Patients in the two study arms had similar demographic profiles. Those receiving preoperative stenting had a higher likelihood of a laparoscopic resection (P < 0.001). The emergency surgery group had a higher rate of postoperative complications (P = 0.024), rate of intensive care unit admission (P = 0.013) and longer total length of hospital stay (9 vs 12 days, P = 0.001). With a median follow‐up of 26.5 and 31.3 months for the stenting and surgical resection groups, there was no difference in overall and disease‐free survival (overall survival 30 vs 31 months, P = 0.858; disease‐free survival 13 vs 12 months, P = 0.989). There was no difference in the rate of systemic recurrence (8 vs 13, P = 0.991).

Conclusion

Stenting as a bridge to surgery is a safe strategy for acute left‐sided colonic obstruction with improved short‐term outcome and comparable long‐term oncological results.