bluuebunny/crossref_metadata_2025 huggingface dataset:
Caspofungin‐induced in‐vitro post‐antifungal effect and its impact on adhesion related traits of oral Candida dubliniensis and Candida albicans isolates
Authors: Ellepola Arjuna Nishantha Bandara , Chandy Rachel , Khan Zia Uddin , Samaranayake Lakshman Perera
Published: February 2016

Adhesion to buccal epithelial cells (BEC) and denture acrylic surfaces (DAS), germ tube (GT) formation and cell surface hydrophobicity (CSH) are all virulence traits involved in the pathogenicity of Candida. Post‐antifungal effect (PAFE) also have a bearing on pathogenicity and virulence of Candida. Candida dubliniensis is associated with oral and systemic candidosis, which can be managed with caspofungin. There is no published information on caspofungin‐induced PAFE and its impact on adhesion traits of C. dubliniensis isolates. Thus, the purpose of this investigation was to determine the in vitro duration of PAFE on 20 C. dubliniensis isolates following transient exposure to caspofungin. Furthermore the impacts of caspofungin‐induced PAFE on adhesion to BEC and DAS, GT formation and CSH of these isolates were also determined. After establishing the minimum inhibitory concentration (MIC) of caspofungin, C. dubliniensis isolates were exposed to sub‐lethal concentrations (×3 MIC) of caspofungin for 1 hr. Thereafter the duration of PAFE, adhesion to BEC and DAS, GT formation and CSH were determined by previously described in‐vitro assays. MIC (μg/mL) of C. dubliniensis isolates to caspofungin ranged from 0.004 to 0.19. Caspofungin‐induced mean PAFE on C. dubliniensis isolates was 2.17 hr. Exposure to caspofungin suppressed the ability of C. dubliniensis isolates to adhere to BEC and DAS, form GT and CSH by 69.97%, 71.95%, 90.06% and 32.29% (P < 0.001 for all), respectively. Thus, transient exposure of C. dubliniensis isolates to caspofungin produces an antifungal effect not only by suppressing its growth but also by altering its adhesion traits.
Density‐dependent population dynamics in Aedes aegypti slow the spread of wMel Wolbachia
Authors: Hancock Penelope A. , White Vanessa L. , Callahan Ashley G. , Godfray Charles H. J. , Hoffmann Ary A. , Ritchie Scott A.
Published: February 2016

Field release of endosymbiotic Wolbachia bacteria into wild Aedes aegypti mosquito populations is a promising strategy for biocontrol of dengue. This strategy requires successful Wolbachia invasion through the mosquito vector population. Natural variation in mosquito fitness due to density‐dependent competition for limited food resources may influence Wolbachia invasion. We know little about these effects, largely because our understanding of density‐dependent dynamics in mosquito populations is limited.

We developed an empirical model of A. aegypti–Wolbachia dynamics where food resources available to the developing larvae are limited. We assessed the extent of density‐dependent regulation in our A. aegypti population using a Bayesian statistical model that estimates the temporal variation in mosquito fitness components. We monitored the spread of Wolbachia and assessed the effect of the bacteria on larval fitness components.

We demonstrate that mosquito population growth is regulated by strong larval density‐dependent variation in mosquito fitness components. Wolbachia spread was slowed by this heterogeneity in mosquito fitness, which reduces the capacity of the bacteria to invade. However, we found no evidence that Wolbachia affects larval fitness components.

Synthesis and applications. We demonstrate that the extent and form of density‐dependent dynamics in the host population can have a major influence on Wolbachia invasion. These findings help explain slow Wolbachia invasion rates and indicate that the success of field release strategies for dengue control can depend on attaining high Wolbachia frequencies in the mosquito population.
Walking as a social practice: dispersed walking and the organisation of everyday practices
Authors: Harries Tim , Rettie Ruth
Published: February 2016

This paper uses social practice theory to study the interweaving of walking into everyday practices and considers how greater awareness of everyday walking can influence its position within the organisation and scheduling of everyday life. Walking is of policy interest because of its perceived benefits for health. This paper asserts that increased awareness of everyday walking allows users to become more active without having to reschedule existing activities. Using Schatzki's distinction between dispersed and integrative practices, it argues that increasing awareness of dispersed walking can enlist walking into the teleoaffective organisation of some social practices and prompt the performance of new ‘health practices’ within everyday domains of life such as shopping and employment. While this analysis offers useful insights for the design of behaviour change strategies, it also points to some unintended consequences of using digital feedback to increase walking awareness. In directing the gaze of participants at one particular element of their daily practices, the paper suggests, digital walking feedback provides a ‘partial’ view of practices: by highlighting the exercise value of walking at the expense of other values it can prompt feedback recipients to pass moral judgements on themselves based on this partial view.

A Virtual Abstract of this paper can be found at: https://youtu.be/WV7DUnKD5Mw
Influence of Water Activity on Thermal Resistance of Microorganisms in Low‐Moisture Foods: A Review
Authors: Syamaladevi Roopesh M. , Tang Juming , Villa‐Rojas Rossana , Sablani Shyam , Carter Brady , Campbell Gaylon
Published: February 2016

A number of recent outbreaks related to pathogens in low‐moisture foods have created urgency for studies to understand the possible causes and identify potential treatments to improve low‐moisture food safety. Thermal processing holds the potential to eliminate pathogens such as Salmonella in low‐moisture foods. Water activity (aw) has been recognized as one of the primary factors influencing the thermal resistance of pathogens in low‐moisture foods. But most of the reported studies relate thermal resistance of pathogens to aw of low‐moisture foods at room temperature. Water activity is a thermodynamic property that varies significantly with temperature and the direction of variation is dependent on the product component. Accurate methods to determine aw at elevated temperatures are needed in related research activities and industrial operations. Adequate design of commercial thermal treatments to control target pathogens in low‐moisture products requires knowledge on how aw values change in different foods at elevated temperatures. This paper presents an overview of the factors influencing the thermal resistance of pathogens in low‐moisture foods. This review focuses on understanding the influence of water activity and its variation at thermal processing temperature on thermal resistance of pathogens in different low‐moisture matrices. It also discusses the research needs to relate thermal resistance of foodborne pathogens to aw value in those foods at elevated temperatures.
Development of oligonucleotide microarrays for simultaneous multi‐species identification of Phellinus tree‐pathogenic fungi
Authors: Tzean Yuh , Shu Po‐Yao , Liou Ruey‐Fen , Tzean Shean‐Shong
Published: February 2016

Polyporoid Phellinus fungi are ubiquitously present in the environment and play an important role in shaping forest ecology. Several species of Phellinus are notorious pathogens that can affect a broad variety of tree species in forest, plantation, orchard and urban habitats; however, current detection methods are overly complex and lack the sensitivity required to identify these pathogens at the species level in a timely fashion for effective infestation control. Here, we describe eight oligonucleotide microarray platforms for the simultaneous and specific detection of 17 important Phellinus species, using probes generated from the internal transcribed spacer regions unique to each species. The sensitivity, robustness and efficiency of this Phellinus microarray system was subsequently confirmed against template DNA from two key Phellinus species, as well as field samples collected from tree roots, trunks and surrounding soil. This system can provide early, specific and convenient detection of Phellinus species for forestry, arboriculture and quarantine inspection, and could potentially help to mitigate the environmental and economic impact of Phellinus‐related diseases.
Towards the development of multifunctional molecular indicators combining soil biogeochemical and microbiological variables to predict the ecological integrity of silvicultural practices
Authors: Peck Vincent , Quiza Liliana , Buffet Jean‐Philippe , Khdhiri Mondher , Durand Audrey‐Anne , Paquette Alain , Thiffault Nelson , Messier Christian , Beaulieu Nadyre , Guertin Claude , Constant Philippe
Published: February 2016

The impact of mechanical site preparation (MSP) on soil biogeochemical structure in young larch plantations was investigated. Soil samples were collected in replicated plots comprising simple trenching, double trenching, mounding and inverting site preparation. Unlogged natural mixed forest areas were used as a reference. Analysis of soil nutrients, abundance of bacteria and gas exchanges unveiled no significant difference among the plots. However, inverting site preparation resulted in higher variations of gas exchanges when compared with trenching, mounding and unlogged natural forest. A combination of the biological and physicochemical variables was used to define a multifunctional classification of the soil samples into four distinct groups categorized as a function of their deviation from baseline ecological conditions. According to this classification model, simple trenching was the approach that represented the lowest ecological risk potential at the microsite level. No relationship was observed between MSP method and soil bacterial community structure as assessed by high‐throughput sequencing of bacterial 16S rRNA gene; however, indicator genotypes were identified for each multifunctional soil class. This is the first identification of multifunctional molecular indicators for baseline and disturbed ecological conditions in soil, demonstrating the potential of applied microbial ecology to guide silvicultural practices and ecological risk assessment.
pophelper: an R package and web app to analyse and visualize population structure
Authors: Francis R. M.
Published: February 2016

Thepophelper rpackage and web app are software tools to aid in population structure analyses. They can be used for the analyses and visualization of output generated from population assignment programs such asadmixture,structureandtess. Some of the functions include parsing output run files to tabulate data, estimatingKusing the Evanno method, generating files forclumppand functionality to create barplots. These functions can be streamlined into standardranalysis workflows. The latest version of the package is available ongithub(https://github.com/royfrancis/pophelper). An interactive web version of thepophelperpackage is available which covers the same functionalities as therpackage version with features such as interactive plots, cluster alignment during plotting, sorting individuals and ordering of population groups. The interactive version is available athttp://pophelper.com/.
Direct Versus Video Laryngoscopy Using the C‐MAC for Tracheal Intubation in the Emergency Department, a Randomized Controlled Trial
Authors: Driver Brian E. , Prekker Matthew E. , Moore Johanna C. , Schick Alexandra L. , Reardon Robert F. , Miner James R.
Published: February 2016

Background

Direct laryngoscopy (DL) has long been the most common approach for emergency endotracheal intubation, although the use of video laryngoscopy (VL) is becoming more widespread. Current observational data suggest that VL has higher first‐pass success, although randomized trials are lacking.

Objectives

The objective was to compare first‐pass success in patients undergoing emergency intubation with DL or VL using a C‐MAC device.

Methods

This was an open‐label, prospective, randomized, controlled trial in an academic emergency department of patients undergoing emergency intubation with a plan of DL for the first attempt. Patients were randomly assigned in a 1:1 ratio to either DL or VL using a C‐MAC device for the first intubation attempt. The primary outcome was first‐pass success. Secondary outcomes included time to intubation, development of aspiration pneumonia, and hospital length of stay (LOS). The study was registered at Clinicaltrials.gov, number NCT01710891.

Results

A total of 198 patients were enrolled and intubated with either DL (n = 95) or VL (n = 103). First‐attempt success was 86 and 92% for the DL and VL groups, respectively (difference = −5.9%, 95% confidence interval = −14.5% to 2.7%, p = 0.18). Time to intubation, rates of aspiration pneumonia, and hospital LOS were not different between the two groups.

Conclusions

In patients undergoing emergency intubation in whom DL was planned for the first attempt, we did not detect a difference between VL or DL using the C‐MAC device in first‐pass success, duration of intubation attempt, aspiration pneumonia, or hospital LOS.
Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice
Authors: Frei R. B. , Luschnig P. , Parzmair G. P. , Peinhaupt M. , Schranz S. , Fauland A. , Wheelock C. E. , Heinemann A. , Sturm E. M.
Published: February 2016

Background

Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2‐arachidonoylglycerol (2‐AG) has been proposed to elicit eosinophil migration in a CB2 receptor/Gi/o‐dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2‐AG into eicosanoids. Here, we explored the direct contribution of specific CB2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo.

Methods

In vitro studies including CB2 expression, adhesion and migratory responsiveness, respiratory burst, degranulation, and calcium mobilization were conducted in human peripheral blood eosinophils and mouse bone marrow‐derived eosinophils. Allergic airway inflammation was assessed in mouse models of acute OVA‐induced asthma and directed eosinophil migration.

Results

CB2 expression was significantly higher in eosinophils from symptomatic allergic donors. The selective CB2 receptor agonist JWH‐133 induced a moderate migratory response in eosinophils. However, short‐term exposure to JWH‐133 potently enhanced chemoattractant‐induced eosinophil shape change, chemotaxis, CD11b surface expression, and adhesion as well as production of reactive oxygen species. Receptor specificity of the observed effects was confirmed in eosinophils from CB2 knockout mice and by using the selective CB2 antagonist SR144528. Of note, systemic application of JWH‐133 clearly primed eosinophil‐directed migration in vivo and aggravated both AHR and eosinophil influx into the airways in a CB2‐specific manner. This effect was completely absent in eosinophil‐deficient ∆dblGATA mice.

Conclusion

Our data indicate that CB2 may directly contribute to the pathogenesis of eosinophil‐driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB2‐mediated priming of eosinophils. Hence, antagonism of CB2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.
Efficacy of a therapeutic treatment using gas‐filled microbubble‐associated phospholipase A2 in a mouse model of honeybee venom allergy
Authors: Corthésy B. , Lassus A. , Terrettaz J. , Tranquart F. , Bioley G.
Published: February 2016

Background

Venom immunotherapy is efficient to desensitize people suffering from insect sting allergies. However, the numerous injections required over several years and important risks of severe side reactions complicate the widespread use of immunotherapy. In the search for novel approaches to blunt the overwhelming pro‐allergic Th2 response, we evaluated the therapeutic efficacy of a treatment based on a denatured form of the major allergen, phospholipase A2, associated with microbubbles (PLA2denat‐MB) in a mouse model of honeybee venom allergy.

Methods

Antibodies measured by ELISA, T‐cell responses assessed by CFSE‐based proliferation assays and ELISA, and basophil degranulation were examined after PLA2denat‐MB‐based therapeutic treatment of sensitized mice. Mice were challenged with a lethal dose of PLA2 to evaluate protection against anaphylaxis.

Results

Therapeutic subcutaneous administration of two different PLA2denat‐MB formulations, in contrast to PLA2denat alone, reduced allergic symptoms and protected all mice from anaphylaxis‐mediated death after allergen challenge. At the functional level, the use of PLA2denat decreased IgE‐mediated basophil degranulation as compared to the native form of the allergen. In comparison with PLA2denat alone, both PLA2denat‐MB formulations decreased allergen‐specific Th2 CD4 T‐cell reactivity. At the mechanistic level, PLA2denat‐MB containing 20% palmitic acid and PEG induced PLA2‐specific IgA and increased Foxp3+ Treg frequencies and TGF‐β production, whereas the formulation bearing 80% palmitic acid triggered the production of IFN‐γ, IgG2a, and IgG3.

Conclusions

In contrast to conventional PLA2 subcutaneous immunotherapy, the therapeutic administration of PLA2‐MB treatment to mice that already had established allergy to PLA2 protects all subsequently challenged animals.
Preclinical and first‐in‐human phase I studies of KW‐2450, an oral tyrosine kinase inhibitor with insulin‐like growth factor receptor‐1/insulin receptor selectivity
Authors: Schwartz Gary K. , Dickson Mark A. , LoRusso Patricia M. , Sausville Edward A. , Maekawa Yoshimi , Watanabe Yasuo , Kashima Naomi , Nakashima Daisuke , Akinaga Shiro
Published: February 2016

Numerous solid tumors overexpress or have excessively activated insulin‐like growth factor receptor‐1 (IGF‐1R). We summarize preclinical studies and the first‐in‐human study of KW‐2450, an oral tyrosine kinase inhibitor with IGF‐1R and insulin receptor (IR) inhibitory activity. Preclinical activity of KW‐2450 was evaluated in various in vitro and in vivo models. It was then evaluated in a phase I clinical trial in 13 patients with advanced solid tumors (NCT00921336). In vitro, KW‐2450 inhibited human IGF‐1R and IR kinases (IC50 7.39 and 5.64 nmol/L, respectively) and the growth of various human malignant cell lines. KW‐2450 40 mg/kg showed modest growth inhibitory activity and inhibited IGF‐1‐induced signal transduction in the murine HT‐29/GFP colon carcinoma xenograft model. The maximum tolerated dose of KW‐2450 was 37.5 mg once daily continuously; dose‐limiting toxicity occurred in two of six patients at 50 mg/day (both grade 3 hyperglycemia) and in one of seven patients at 37.5 mg/day (grade 3 rash). Four of 10 evaluable patients showed stable disease. Single‐agent KW‐2450 was associated with modest antitumor activity in heavily pretreated patients with solid tumors and is being further investigated in combination therapy with lapatinib/letrozole in patients with human epidermal growth factor receptor 2‐postive metastatic breast cancer.
Efficient Synthesis and Biological Evaluation of a Novel Series of 1,5‐Benzodiazepine Derivatives as Potential Antimicrobial Agents
Authors: An Ying‐shuang , Hao Zhen‐fang , Zhang Xiu‐jun , Wang Lan‐zhi
Published: February 2016

A series of novel 1,5‐benzodiazepine derivatives were rationally designed and synthesized following the principle of the superposition of bioactive substructures by the combination of 1,5‐benzodiazepine, pyridine (phenyl), and an ester group. The structures of the target compounds were determined by 1H NMR, 13C NMR, MS, IR, and elemental analysis. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi C. neoformans, C. neoformans clinical isolates (ATCC 32264), C. albicans (ATCC 10231), Gram‐negative bacterium E. coli (ATCC 44752), and Gram‐positive bacterium S. aureus (ATCC 25923). The results of the bioactive assay demonstrated that most of the tested compounds exhibited variable inhibitory effects on the growth of the tested microorganisms. All the active compounds showed better antifungal activity than antibacterial activity. Notably, compound 2b displayed the highest activity (MIC = 30 μg/mL) against C. neoformans and (MIC = 31 μg/mL) against C. neoformans clinical isolates. In addition, compound 2a also showed excellent activity against C. neoformans and C. neoformans clinical isolates with minimum inhibitory concentration of 35 and 36 μg/mL, respectively. Compounds 2a and 2b were further studied by evaluating their cytotoxicities, and the results showed that they have relatively low level cytotoxicity for BV2 and 293T cell. Preliminary structure‐activity relationship study on three diverse sets (C‐2, C‐3, and C‐8 positions) of 1,5‐benzodiazepines was performed. The results revealed that the presence of a ‐CH3 group at the C‐8 position had a positive effect on the inhibitory activity of these compounds. Additionally, the 2‐pyridyl group at the C‐2 position may be a pharmacophore and ‐COOC2H5 at C‐3 position is the best substituent for the maintenance of antimicrobial activities.
Structural and Functional Characterization of Hirudin P6 Derived Novel Bivalent Thrombin Inhibitors – Studying the Effect of Linker Length and Glycosylation on Their Function
Authors: Shabareesh PRV , Kaur Kanwal J.
Published: February 2016

HirudinP6 is a glycosylated and sulfated high affinity thrombin inhibitory protein isolated from Hirudineria manillensis. In this study, designing of novel bivalent thrombin inhibitory peptides based on this hirudin isoform is described. The structural and functional impact of varying linker length and glycosylation on their inhibitory potencies and binding kinetics were assessed. The bivalent peptides were obtained by tethering an active site blocking fPRP motif with the carboxy terminal 22 residue segment of hirudin P6 (HP642–63) by varying number of glycine residues in the linker region. Among them, analog BiG1‐HP6 inhibited thrombin with a Ki of 5.12 nm which was comparable to that of glycosylated (disaccharide bearing) and non‐sulfated full length hirudin P6 protein (Ki = 6.38 nm). Binding kinetics studies revealed increasing linker length can decrease the association rates of peptide─thrombin interactions. Similarly, glycosylation was found to negatively modulate the inhibitory potencies of these peptides by decreasing their rates of association with thrombin. Molecular docking studies revealed that increasing linker length can compromise the electrostatic interactions with the prime subsite residues of thrombin and provided structural explanation for the observed effect of linker length on association rates. These findings thus enhance our understanding of thrombin─(glyco)peptide interactions and provide key insights into the designing of efficient thrombin inhibitors and allosteric modulators of therapeutic potential.
Computational Study and Modified Design of Selective Dopamine D3 Receptor Agonists
Authors: Duan Xinli , Zhang Xin , Xu Binglin , Wang Fang , Lei Ming
Published: February 2016

Dopamine D3 receptor (D3R) is considered as a potential target for the treatment of nervous system disorders, such as Parkinson's disease. Current research interests primarily focus on the discovery and design of potent D3 agonists. In this work, we selected 40 D3R agonists as the research system. Comparative molecular field analysis (CoMFA) of three‐dimensional quantitative structure–activity relationship (3D‐QSAR), structure–selectivity relationship (3D‐QSSR), and molecular docking was performed on D3 receptor agonists to obtain the details at atomic level. The results indicated that both the CoMFA model (r2 = 0.982, q2 = 0.503, = 0.893, SEE  = 0.057, F = 166.308) for structure–activity and (r2 = 0.876, q2 = 0.436, = 0.828, F = 52.645) for structure–selectivity have good predictive capabilities. Furthermore, docking studies on three compounds binding to D3 receptor were performed to analyze the binding modes and interactions. The results elucidate that agonists formed hydrogen bond and hydrophobic interactions with key residues. Finally, we designed six molecules under the guidance of 3D‐QSAR/QSSR models. The activity and selectivity of designed molecules have been improved, and ADMET properties demonstrate they have low probability of hepatotoxicity (<0.5). These results from 3D‐QSAR/QSSR and docking studies have great significance for designing novel dopamine D3 selective agonists in the future.
The challenge of measuring IL‐33 in serum using commercial ELISA: lessons from asthma
Authors: Ketelaar M. E. , Nawijn M. C. , Shaw D. E. , Koppelman G. H. , Sayers I.
Published: February 2016

Background

Interleukin‐33 (IL‐33) has been subject of extensive study in the context of inflammatory disorders, particularly in asthma. Many human biological samples, including serum, have been used to determine the protein levels of IL‐33, aiming to investigate its involvement in asthma. Reliable methods are required to study the association of IL‐33 with disease, especially considering the complex nature of serum samples.

Objective

We evaluated four IL‐33 ELISA kits, aiming to determine a robust and reproducible approach to quantifying IL‐33 in human serum from asthma patients.

Methods

IL‐33 levels were investigated in serum of well‐defined asthma patients by the Quantikine, DuoSet (both R&D systems), ADI‐900‐201 (Enzo Life Sciences), and SKR038 (GenWay Biotech Inc San Diego USA) immunoassays, as well as spiking experiments were performed using recombinant IL‐33 and its soluble receptor IL‐1RL1‐a.

Results

We show that 1) IL‐33 is difficult to detect by ELISA in human serum, due to lack of sensitivity and specificity of currently available assays; 2) human serum interferes with IL‐33 quantification, in part through IL‐1RL1‐a; and 3) using non‐serum certified kits may lead to spurious findings.

Conclusion and Clinical Relevance

If IL‐33 is to be studied in the serum of asthma patients and other diseases, a more sensitive and specific assay method is required, which will be vital for further understanding and targeting of the IL‐33/IL‐1RL1 axis in human disease.
Acylated and unacylated ghrelin during OGTT in Prader‐Willi syndrome: support for normal response to food intake
Authors: Kuppens R.J. , Delhanty P.J.D. , Huisman T.M. , van der Lely A.J. , Hokken‐Koelega A.C.S.
Published: February 2016

Background

Prader‐Willi syndrome (PWS) is characterized by hyperphagia with impaired satiety. PWS patients have very high acylated ghrelin (AG) with normal unacylated ghrelin (UAG) levels, resulting in an elevated AG/UAG ratio, suggesting an intrinsic defect in the ghrelin regulation. Normally, food intake induces satiety and a drop in AG and UAG levels, but it is unknown if these levels also decline in PWS.

Objective

To evaluate whether the high AG levels in PWS decline in response to glucose intake during an oral glucose tolerance test (OGTT), and to investigate the effects of growth hormone (GH) treatment on this response.

Method

Serum levels of AG, UAG and AG/UAG ratio during an OGTT were determined in 24 GH‐treated patients with PWS (median age 19·0, range 14·2–25·9 years) and in 10 GH‐stop patients (of whom five were in GH‐treated group; 18·5, 14·5–20·3 years).

Results

In GH‐treated and GH‐stop young adults with PWS, there was a sharp decline of AG levels and a decrease of UAG levels in the first 30 min after the glucose load, which resulted in a lower AG/UAG ratio. GH‐treated patients had significantly lower AG levels than GH‐stop patients at baseline and during the OGTT. All UAG levels and AG/UAG ratios were lower in the GH‐treated patients, although not significantly.

Conclusions

In young adults with PWS, an oral glucose load significantly reduces AG and UAG levels, suggesting normal regulation of the ghrelin axis by food intake. GH treatment results in lower AG levels at baseline and during OGTT, suggesting a more favourable metabolic profile. Our findings might suggest that the impaired satiety is not the result of an abnormal response of the orexigenic ghrelin to food intake.
Serum thyroglobulin as a biomarker of iodine deficiency in adult populations
Authors: Krejbjerg Anne , Bjergved Lena , Bülow Pedersen Inge , Carlé Allan , Knudsen Nils , Perrild Hans , Ovesen Lars , Banke Rasmussen Lone , Laurberg Peter
Published: February 2016

Objective

To clarify which factors may influence the serum Tg level in an adult population and how this may affect Tg as a biomarker of iodine deficiency (ID).

Design and methods

Two identical cross‐sectional studies were performed before (C1a: 1997–98, n = 4649) and after (C2: 2004–05, n = 3570) the Danish mandatory iodine fortification (IF) of salt (2000). Additionally, a follow‐up study of C1a was performed after IF (C1b: 2008–10, n = 2465). The studies took place in two regions with mild (Copenhagen) and moderate (Aalborg) ID before IF. Serum Tg was measured by immunoradiometric method and investigated as outcome variable in multivariate models.

Results

Multiple factors were associated with serum Tg. Some were directly related to iodine intake (cohort, urinary iodine concentration (UIC) level and region), and some were likely mediators of iodine intake effects on Tg (thyroid nodularity, thyroid size and autonomy with low TSH). Others were caused by Tg assay interference (Tg‐Ab positivity), aggravation of ID (childbirths and smoking) or TSH stimulation of the thyroid. Estimated 24‐h urinary iodine excretion was a more sensitive predictor of Tg than UIC. Iodine supplement users had low median Tg values compared with nonusers both before and after IF.

Conclusions

Multiple factors should be taken into consideration when evaluating Tg as a marker of ID in adult populations, and the Tg results may depend on the assay used. Still, Tg is a sensitive marker of ID. We suggest including a reference population with known sufficient iodine intake when Tg is used to evaluate ID.
Survival following salvage abdominoperineal resection for persistent and recurrent squamous cell carcinoma of the anus: do these disease categories affect survival?
Authors: Severino N. P. , Chadi S. A. , Rosen L. , Coiro S. , Choman E. , Berho M. , Wexner S. D.
Published: February 2016

Aim

This study aimed to investigate the results of salvage abdominoperineal excision (APR) in patients with persistent or recurrent squamous cell carcinoma of the anus (SCCA).

Method

Patients with anal neoplasia were identified from a prospective database. Patients with invasive SCCA with demonstrated failure of chemoradiation therapy (CRT) who underwent salvage APR for one of three disease categories (persistent, < 6 months post‐CRT; early recurrent, 6–24 months post‐CRT; late recurrent, > 24 months post‐CRT) were included. The primary outcome was overall survival after salvage APR. Tumour size, metastatic lymph nodes (LN), circumferential resection margin positivity (CRM) and neurolymphovascular invasion (NLVI) were correlated with the outcome.

Results

Thirty‐six patients with a median 3‐year overall survival of 46% (median follow‐up 24 months) underwent salvage APR due to persistent or recurrent SCCA (14 men, mean age 59 years). Eleven (31%) patients were diagnosed with persistent disease, 17 (47%) with early and 8 (22%) with late recurrence. Two‐year overall survival of Stage 0/I/II and III/IV disease was 81.5% and 33.74%, respectively (P = 0.022). Overall disease stage was associated with disease categorization (P = 0.009): patients with persistent disease or early recurrence had a significantly higher disease stage than patients with late recurrence (OR = 20.9 and 17.2). Despite apparently improved survival in patients with late disease recurrence on live table analysis, no significant difference was identified in overall survival when stratified by disease category on log‐rank test analysis.

Conclusion

Persistent and recurrent disease does not show any significant difference in survival, but patients with late recurrence may have a better prognosis.
Differences in screening vs non‐screening colonoscopy: scope for improvement?
Authors: Ahmed S. , Naumann D. N. , Karandikar S.
Published: February 2016

Aim

Colonoscopy performed as part of the NHS Bowel Cancer Screening Programme (BCSP) is of high standard as measured using global rating scale (GRS) criteria. Screening practitioners also provide a non‐screening colonoscopy service. The current study compares colonoscopy quality indicators between screening and non‐screening groups performed by a single practitioner using the GRS.

Method

Patient details were obtained for all consecutive colonoscopies between 2007 and 2014 performed by a single screening practitioner. Data were collected retrospectively from electronic patient records; BCSP Exeter database and non‐screening colonoscopies were compared. Data included patient demographics (age, gender), sedation, and the GRS data including caecal intubation, adenoma and neoplasia detection rates.

Results

In all, 1961 colonoscopy procedures (1067 screening and 894 non‐screening) were identified; 57% were men. Mean (SD) age for all patients was 64 (± 10.4) years. Non‐screening patients were younger [62 (± 14) vs 66 (± 4.8) years; P < 0.05] and were less likely to be men (51.5% vs 61.9%; P < 0.05) than their screening counterparts. Caecal intubation was more successful in screening patients [1027/1067 (96.3%)] than non‐screening patients [805/894 (90%)]; P < 0.05. Adenoma detection rate was higher in the screening (46.8 ± 4.4) than non‐screening (26.3 ± 11.8) group; P < 0.05. There were no differences in neoplasia detection. Polypectomy was more likely (55.5% vs 30.2%) and polyp retrieval more successful (97.5% vs 86.7%) in the screening group.

Conclusion

Screening and non‐screening colonoscopy differ in the GRS domains of completion and pathology detection. These differences need to be acknowledged when comparing screeners and non‐screeners using GRS within units.
Transanal completion proctectomy after total colectomy and ileal pouch‐anal anastomosis for ulcerative colitis: a modified single stapled technique
Authors: de Buck van Overstraeten A. , Wolthuis A. M. , D'Hoore A.
Published: February 2016

Aim

Minimally invasive surgery has proved its efficacy for the surgical treatment of ulcerative colitis (UC). The recent evolution in single port (SP) surgery together with transanal rectal surgery could further facilitate minimally invasive surgery in UC patients. This technical note describes a technical modification for single stapled anastomoses in patients undergoing transanal completion proctectomy and ileal pouch‐anal anastomosis (ta‐IPAA) for UC.

Methods

A step‐by‐step approach of the ta‐IPAA in UC is described, including pictures and a video illustration.

Results

We describe a ta‐IPAA with SP laparoscopy at the ileostomy site. All patients underwent a total colectomy with end‐ileostomy for therapy refractory UC in a first step. Colectomy was done by multiport laparoscopy in six patients, while the ileostomy site was used as single port access in five patients. In all 11 patients the stoma site was used for SP mobilization of the mesenteric root and fashioning of the J‐pouch. Completion proctectomy was done using a transanal approach. A single stapled anastomosis was performed in all patients. An 18 French catheter was used to approximate the pouch to the rectal cuff.

Conclusion

A technical modification of the single stapled anastomosis facilitates the formation of the ta‐IPAA, further reducing invasiveness in UC patients.
Impact of EGF,IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study
Authors: Mueller Jessica L. , King Lindsay Y. , Johnson Kara B. , Gao Tian , Nephew Lauren D. , Kothari Darshan , Simpson Mary Ann , Zheng Hui , Wei Lan , Corey Kathleen E. , Misdraji Joseph , Lee Joon Hyoek , Lin M. Valerie , Gogela Neliswa A. , Fuchs Bryan C. , Tanabe Kenneth K. , Gordon Fredric D. , Curry Michael P. , Chung Raymond T.
Published: February 2016

Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non‐transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver‐related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow‐up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non‐AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93–4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R‐CC/D‐CC 8/12[67%], R‐non‐CC/D‐CC or R‐CC/D‐non‐CC 23/52[44%], R‐non‐CC/D‐non‐CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.
Fatal outcome of human coronavirus NL63 infection despite successful viral elimination by IFN‐alpha in a patient with newly diagnosed ALL
Authors: Mayer Karin , Nellessen Cordula , Hahn‐Ast Corinna , Schumacher Martin , Pietzonka Sandra , Eis‐Hübinger Anna M. , Drosten Christian , Brossart Peter , Wolf Dominik
Published: February 2016

Introduction

Human coronavirus NL63 (HCoV‐NL63) is one of four common human respiratory coronaviruses. Despite high incidence, HCoV infections are grossly understudied. We here report a case of HCoV infection in a leukemia patient with fatal ARDS despite successful virus elimination by pegylated interferon‐alpha (PEG‐IFN‐α).

Case

The 27‐year‐old female pre‐T‐ALL patient was treated according to the German‐Multicenter Trial for Adult ALL protocol. No relevant infectious complications were seen until day 35 when the neutropenic patient developed fever without any clinical focus. Antibiotic prophylaxis was switched to meropenem. The patient deteriorated rapidly with respiratory failure due to ARDS. Anti‐infectious therapy was escalated to additional linezolid and liposomal amphotericine‐B. BAL revealed a significant viral load of HCoV‐NL63. Based on successful application of PEG‐IFN against the related SARS coronavirus in animal experiments, a single injection of 180 μg PEG‐IFN‐α2b was applied. Despite immediate initiation of treatment and elimination of virus in subsequent tests, the progressive lung failure led to death 7 d after onset of fever with massive lung bleeding as a consequence of diffuse alveolar hemorrhage.

Conclusion

This report emphasizes the fatal consequences of common respiratory virus infections in immunocompromised patients. HCoV‐NL63 replication can be reduced by treatment with peg‐IFN if diagnosed early.
Neurothrombectomy in acute ischaemic stroke: a prospective single‐centre study and comparison with randomized controlled trials
Authors: Nikoubashman O. , Jungbluth M. , Schürmann K. , Müller M. , Falkenburger B. , Tauber S. C. , Wiesmann M. , Schulz J. B. , Reich A.
Published: February 2016

Background and purpose

In the last few months five multicentre, randomized controlled trials (RCTs) unequivocally showed the superiority of mechanical thrombectomy in large vessel occlusion acute ischaemic stroke compared to systemic thrombolysis. Despite varying inclusion criteria and time intervals from onset to revascularization overall increases of good functional outcome between 55% and 81% were reported. However, only a minority of screened patients (approximately 1%) were eligible for intra‐arterial (IA) therapy.

Methods

An investigator‐initiated, single‐centre, prospective and blinded end‐point analysis was performed of 3123 consecutive patients with acute ischaemic stroke presenting between February 2010 and December 2014.

Results

One hundred and fifty‐four patients [4.9%, age (years) mean (SD), median (interquartile range) 71.2 (±14), 74.7 (65.9–81.4)] met the inclusion criteria of sparse early ischaemic signs on initial standard cranial computed tomography (CT) (ASPECT score ≥7), large vessel occlusion in the anterior circulation on CT angiography and start of treatment within 6 h of onset of symptoms. After consensual interdisciplinary treatment decisions 130 patients (4.2%) received IA treatment – in the majority stent‐assisted thrombectomy in combination with intravenous (IV) recombinant tissue plasminogen activator – and 24 patients (0.7%) standard IV thrombolysis. On 3 months’ follow‐up an overall significant improvement of disability (P = 0.05) as measured by the modified Rankin Scale was shown in favour of the IA treatment group. Good functional outcome was achieved in about twice as many patients (IA vs. IV, 41.2% vs. 21.2%; P = 0.078).

Conclusion

By choosing pragmatic inclusion criteria state‐of‐the‐art IA therapy of a specialized tertiary stroke centre can be safely applied under real‐world conditions to a higher percentage of patients with similar success to the recently published RCTs.
Septic peritonitis in a Percheron mare associated withClostridium haemolyticum
Authors: Hepworth‐Warren K. L. , Hay Kraus B. L. , Wong D. M. , Krull A. C. , Metcalf G. L.
Published: February 2016

This report describes an 11‐year‐old Percheron mare that presented with signs of colic and was ultimately diagnosed with bacterial peritonitis of unknown origin. Bacterial culture of a peritoneal fluid sample isolated 2 Clostridial species, one of which was strongly suspected to beClostridium haemolyticum. The horse was markedly hypoalbuminaemic at presentation, leading to the development of low oncotic pressure and ventral oedema. The mare was administered a low molecular weight/low molar substitution hydroxyethyl starch solution in conjunction with other therapies that resulted in marked improvement of clinical signs. The purpose of this report is to describe the clinical findings associated with equine peritonitis associated withC. haemolyticum, a rarely identified pathogen in the horse. Secondly, this report serves to describe the beneficial effects of tetrastarch administration in a clinical case with severe hypoalbuminaemia and ventral oedema.
A comparative review of fisheries management experiences in the European Union and in other countries worldwide: Iceland, Australia, and New Zealand
Authors: Marchal Paul , Andersen Jesper Levring , Aranda Martin , Fitzpatrick Mike , Goti Leyre , Guyader Olivier , Haraldsson Gunnar , Hatcher Aaron , Hegland Troels Jacob , Le Floc'h Pascal , Macher Claire , Malvarosa Loretta , Maravelias Christos D , Mardle Simon , Murillas Arantza , Nielsen J Rasmus , Sabatella Rosaria , Smith Anthony D M , Stokes Kevin , Thoegersen Thomas , Ulrich Clara
Published: February 2016

This study compares the details and performance of fisheries management between the EU and a selection of other countries worldwide: Iceland, New Zealand, and Australia, which are considered in many respects to be among the most advanced in the world in fisheries management. Fisheries management in the EU, Iceland, Australia, and New Zealand has developed following different paths, despite being based on similar instruments and principles. Iceland, Australia, and New Zealand have been at the forefront of developing management practices such as stakeholder involvement, legally binding management targets (Australia, New Zealand), individual transferable quotas, and discard bans (Iceland, New Zealand). The EU has since the beginning of the 21st century taken significant steps to better involve stakeholders and establish quantitative targets through management plans, and a landing obligation is gradually being implemented from 2015 onward. The management of domestic fisheries resources in Australia, New Zealand, and Iceland has, overall, performed better than in the EU, in terms of conservation and economic efficiency. It should, however, be stressed that, compared to Australia, New Zealand, and Iceland, (i) initial over‐capacity was more of an issue in the EU when management measures became legally binding and also that (ii) EU has been progressive in developing common enforcement standards, on stocks shared by sovereign nations. The situation of EU fisheries has substantially improved over the period 2004–2013 in the northeast Atlantic, with fishery status getting close to that in the other jurisdictions, but the lack of recovery for Mediterranean fish stocks remains a concern.
Treatment of anxiety and depression: medicinal plants in retrospect
Authors: Fajemiroye James O. , da Silva Dayane M. , de Oliveira Danillo R. , Costa Elson A.
Published: February 2016

Anxiety and depression are complex heterogeneous psychiatric disorders and leading causes of disability worldwide. This review summarizes reports on the fundamentals, prevalence, diagnosis, neurobiology, advancement in treatment of these diseases and preclinical assessment of botanicals. This review was conducted through bibliographic investigation of scientific journals, books, electronic sources, unpublished theses and electronic medium such as ScienceDirect and PubMed. A number of the first‐line drugs (benzodiazepine, azapirone, antidepressant tricyclics, monoamine oxidase inhibitors, serotonin selective reuptake inhibitors, noradrenaline reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, etc.) for the treatment of these psychiatric disorders are products of serendipitous discoveries. Inspite of the numerous classes of drugs that are available for the treatment of anxiety and depression, full remission has remained elusive. The emerging clinical cases have shown increasing interests among health practitioners and patients in phytomedicine. The development of anxiolytic and antidepressant drugs of plant origin takes advantage of multidisciplinary approach including but not limited to ethnopharmacological survey (careful investigation of folkloric application of medicinal plant), phytochemical and pharmacological studies. The selection of a suitable plant for a pharmacological study is a basic and very important step. Relevant clues to achieving this step include traditional use, chemical composition, toxicity, randomized selection or a combination of several criteria. Medicinal plants have been and continue to be a rich source of biomolecule with therapeutic values for the treatment of anxiety and depression.