bluuebunny/crossref_metadata_2025 huggingface dataset:
Disentangling associational effects: both resource density and resource frequency affect search behaviour in complex environments
Authors: Verschut Thomas A. , Becher Paul G. , Anderson Peter , Hambäck Peter A.
Published: April 2016

Neighbouring resources have been found to either decrease or increase the likelihood that a consumer organism attacks a focal resource. These phenomena are referred to as associational resistance (AR) and associational susceptibility (AS), respectively. While associational effects have been observed in various field studies, little is known on how resource heterogeneity can cause associational effects.

We used a laboratory approach in which we studied the effects of resource density and frequency in the search behaviour of Drosophila melanogaster as a model organism for olfactory‐guided behaviour in insects. We first determined whether D. melanogaster could discriminate between odour sources that differ quantitatively. Secondly, we determined what the effect of resource density and frequency was on the search behaviour of D. melanogaster by combining these resources into various patch arrangements. Finally, we used the outcome of our experiments to disentangle the role of resource density and frequency in associational effects.

We found that D. melanogaster has the ability to discriminate between quantitatively different resources, but that the attraction to resource density is constrained by an optimum after which attraction decreases. Furthermore, in heterogeneous environments, flies showed a strong preference towards the more apparent resource, leading to AS for the more apparent resources and AR for the less apparent resource. The strength of this interaction increased with a decreasing frequency of the more apparent resource.

These results imply that D. melanogaster mainly selects patches at the level of individual resources. Consequently, when a patch contains qualitatively different resources, the more apparent resource will attract a higher number of flies than the less apparent resource irrespective of the frequency of the apparent resource within the patch.

Our study shows that associational effects can be explained by determining the hierarchical level at which a consumer selects its resources. When a consumer selects resources at the individual level rather than at the patch level, our results can be used to explain the population dynamics of host plants and their associated consumers under field conditions.

A lay summary is available for this article.
Beyond plant–soil feedbacks: mechanisms driving plant community shifts due to land‐use legacies in post‐agricultural forests
Authors: de la Peña Eduardo , Baeten Lander , Steel Hanne , Viaene Nicole , De Sutter Nancy , De Schrijver An , Verheyen Kris
Published: April 2016

Although biotic legacies of past agricultural practices are widespread and increasing in contemporary ecosystems, our understanding of the mechanisms driving such legacies is still poor. Forest understories on former agricultural land show low frequencies and abundance of typical woodland species when compared with ancient forests.

These community shifts have been ascribed to the effects of dispersal limitation. A rarely considered mechanism is that post‐dispersal processes driven by plant‐associated communities determine the poor performance and recruitment of woodland indicators. Given the strong alterations in soil conditions due to former agricultural practices, we hypothesized that (abiotic) plant–soil feedbacks could be a major factor in community shifts.

We addressed this hypothesis by comparing plant‐associated communities in the soil and above the ground in ancient and post‐agricultural alluvial forests; then, we experimentally tested whether the changes in biotic and abiotic soil properties could affect above‐ground herbivore abundance and pressure and plant performance.

Ancient and post‐agricultural communities clearly differed in composition at different levels of the food web. Besides the plant community, we also observed the differences in the microbial and nematode community with increased abundance of root‐feeding nematodes in post‐agricultural soils. The composition of the above‐ground invertebrate community did not differ in ancient and post‐agricultural forest parcels; however, plants growing in post‐agricultural sites showed higher abundance of invertebrate herbivores and suffered more herbivory. Nutrient analyses of soil and plants showed that increased levels of phosphorus (and to a lesser extent, nitrogen) made plants more nutritious for insect herbivores. Laboratory experiments further pointed to this mechanism as an explanation of the poorer performance of woodland indicators in post‐agricultural woodlands.

Our results point to biotic and abiotic plant–soil feedbacks coupled with herbivory as a new mechanism to explain the legacy effects in temperate forests. The modification of the below‐ground community and soil abiotic characteristics by previous agricultural activity affects not only the plant growth but also the plant nutrient content in the compared understorey species, making them more susceptible to above‐ground herbivory. Our results provide one of the first examples of integrating plant–soil feedback and above‐ and below‐ground interactions to explain land‐use legacies.
Dietary niche constriction when invaders meet natives: evidence from freshwater decapods
Authors: Jackson Michelle C. , Grey Jonathan , Miller Katie , Britton J. Robert , Donohue Ian
Published: April 2016

Invasive species are a key driver of global environmental change, with frequently strong negative consequences for native biodiversity and ecosystem processes. Understanding competitive interactions between invaders and functionally similar native species provides an important benchmark for predicting the consequences of invasion. However, even though having a broad dietary niche is widely considered a key factor determining invasion success, little is known about the effects of competition with functionally similar native competitors on the dietary niche breadths of invasive species.

We used a combination of field experiments and field surveys to examine the impacts of competition with a functionally similar native crab species on the population densities, growth rates and diet of the globally widespread invasive red swamp crayfish in an African river ecosystem.

The presence of native crabs triggered significant dietary niche constriction within the invasive crayfish population. Further, growth rates of both species were reduced significantly, and by a similar extent, in the presence of one another. In spite of this, crayfish maintained positive growth rates in the presence of crabs, whereas crabs lost mass in the presence of crayfish. Consequently, over the 3‐year duration of the study, crab abundance declined at those sites invaded by the crayfish, becoming locally extinct at one.

The invasive crayfish had a dramatic effect on ecosystem structure and functioning, halving benthic invertebrate densities and increasing decomposition rates fourfold compared to the crabs. This indicates that replacement of native crabs by invasive crayfish likely alters the structure and functioning of African river ecosystems significantly.

This study provides a novel example of the constriction of the dietary niche of a successful invasive population in the presence of competition from a functionally similar native species. This finding highlights the importance of considering both environmental and ecological contexts in order to predict and manage the impacts of invasive species on ecosystems.
Good reasons to leave home: proximate dispersal cues in a social spider
Authors: Berger‐Tal Reut , Berner‐Aharon Na'ama , Aharon Shlomi , Tuni Cristina , Lubin Yael
Published: April 2016

Natal dispersal is a successful tactic under a range of conditions in spite of significant costs. Habitat quality is a frequent proximate cause of dispersal, and studies have shown that dispersal increases both when natal habitat quality is good or poor. In social species kin competition, favouring dispersal may be balanced by the benefits of group living, favouring philopatry.

We investigated the effect of changes in the local environment on natal dispersal of adult females in a social spider species,Stegodyphus dumicola(Araneae, Eresidae), with a flexible breeding system, where females can breed either within the colony or individually following dispersal.

We manipulated foraging opportunities in colonies by either removing the capture webs or by adding prey and recorded the number of dispersing females around each focal colony, and their survival and reproductive success. We predicted that increasing kin competition should increase dispersal of less‐competitive individuals, while reducing competition could cause either less dispersal (less competition) or more dispersal (a cue indicating better chances to establish a new colony).

Dispersal occurred earlier and at a higher rate in both food‐augmented and web‐removal colonies than in control colonies. Fewer dispersing females survived and reproduced in the web‐removal group than in the control or food‐augmented groups.

The results support our prediction that worsening conditions in web‐removal colonies favour dispersal, whereby increased kin competition and increased energy expenditure on web renewal cause females to leave the natal colony. By contrast, prey augmentation may serve as a habitat‐quality cue; when the surrounding habitat is expected to be of high quality, females assess the potential benefit of establishing a new colony to be greater than the costs of dispersal.
Cluniac Customs Beyond Cluny: Patterns of Use in the Southern Low Countries
Authors: Diehl J. , Vanderputten S.
Published: April 2016

This article examines the ways in which the customary of Cluny was used in monastic communities of the southern Low Countries. Through an examination of an unpublished and little‐known letter concerning liturgical practices that is preserved in a copy of the customary from the monastery of Saint‐Trond, it argues that there was no single use for the customary among monastic communities in the southern Low Countries. Rather, it was a flexible document whose use was dictated more by the local context in which it was deployed and the goals and traditions of particular communities. The letter and the manuscript it contains reveals two possible such uses for the customary: it could operate as an instrument of monastic authority or serve as an inspirational text for Benedictine identity.
A pilot study of the utility of choline PET–CT in prostate cancer biochemical relapse following radical prostatectomy
Authors: Tan Hendrick , Joseph David , Loh Nelson K , McCarthy Michael , Leong Eugene , Siew Teck , Segard Tatiana , Morandeau Laurence , Trevenen Michelle , Francis Roslyn J
Published: April 2016

Introduction

To evaluate the detection rate of positive choline PET–CT and its clinical role in assisting with management decisions and the correlation between positive choline PET–CT and clinical/pathological parameters in prostate cancer patients with biochemical relapse following radical prostatectomy.

Methods

This was a longitudinal observational pilot study of 34 patients who received choline PET–CT scans with biochemical relapse after radical prostatectomy. Variables including peak PSA, PSA doubling time (DT), Gleason score, age, initial PSA at diagnosis, use of ADT prior to PET and initial clinical staging were statistically analysed to assess for independent predictive factors for positive PET findings.

Results

Choline PET–CT was positive in 38.2% of patients (13/34). The only statistically significant predictor for positive PET–CT was the use of ADT prior to PET–CT, with OR 18.7 (95% CI, 2.87–122.45), P < 0.01. Mean peak PSA for patients with positive PET–CT was 5.5 ± 4.8 ng/mL. Patients with positive PET–CT had a mean PSA DT of 5.1 ± 3.8 months and mean total Gleason of 7.6 ± 0.8. Although these variables were not statistically significant, they showed a tendency towards significance. At Receiver Operator Characteristics (ROC) analysis, a peak PSA value of 1.65 ng/mL and PSA DT of 4.4 months were determined to be the optimal cut‐off values predicting positive PET–CT.

Conclusion

Choline PET–CT has its potential as a diagnostic modality enabling the detection of occult prostate cancer recurrence and to differentiate localised disease from systemic disease thus guiding management. Use of ADT prior to PET–CT is a significant predictor of positive PET–CT. Patients with a short PSA DT, high‐peak PSA and high Gleason score should also be considered for choline PET–CT.
Evolution and adaptation of SAR11 and Cyanobium in a saline Tibetan lake
Authors: Oh Seungdae , Zhang Rui , Wu Qinglong L. , Liu Wen‐Tso
Published: April 2016

Lake Qinghai is a unique lacustrine ecosystem located on the Tibetan Plateau and exhibits oligotrophic, alkaline, and saline conditions. Previous studies have focused on the community phylogenetic diversity of bacterioplankton in the ecosystem. This study aimed to address the ecotype diversity of bacterioplankton populations in the unique microbial habitat, using metagenomic sequencing and analysis. Phylogenetic analysis revealed two major bacterial populations: SAR11 IIIa (14% of the total) and Cyanobium (14%). Although the two populations shared high 16S rRNA gene sequence identity (> 98% identity) with their closest marine counterparts, they displayed substantial genomic divergence (≤ 80% average amino acid sequence identity). Comparative genomic analysis identified conservation of carbon and energy storage metabolism (biosynthesis of polyphosphate and polyhydroxyalkanoate) gene operons in the SAR11 IIIa and a cyanate (potential nitrogen source in alkaline conditions) transporter gene operon in the Cyanobium. We further identified genetic signature of positive selection acting on an exodeoxyribonuclease gene of the SAR11 IIIa population, which is potentially associated with DNA repair responsive to strong UV radiation on the high altitude mountain. Taken together, our results revealed the ecosystem‐specific gene content of the bacterioplankton populations and provided new insights into their adaptations unique to the Tibetan lake.
Variability in progeny production and virulence of cyanophages determined at the single‐cell level
Authors: Kirzner Shay , Barak Efrat , Lindell Debbie
Published: April 2016

Little information regarding viral progeny production (burst size) and host mortality (viral virulence) is currently available for environmentally relevant phages. This is partially due to the difficulty in accurately measuring these infection properties with existing methods. Here, we set up a simple system for determining viral virulence and burst size at the single‐cell level following flow cytometric separation of infected cells. We applied this assay to two distinct cyanomyoviruses, Syn9 and S‐TIM5, during infection of two marine Synechococcus strains each. We found that virulence ranged from 44%–82%, differing for the same phage on different hosts. Average burst sizes ranged from 21–43 infective viruses/cell, and differed with host for Syn9, whereas the burst size of S‐TIM5 was similar for both hosts. In addition, virulence and burst sizes were different for the two phages when infecting their common host. Furthermore, wide‐ranging cell‐to‐cell variability was found for single‐cell burst sizes in each of the four interactions, ranging from 2 to over 100 infective viruses/cell. This variability, discerned at both the population and single‐cell levels under controlled laboratory conditions, is likely to be much more complex in natural environments.
Varroa destructor and viruses association in honey bee colonies under different climatic conditions
Authors: Giacobino Agostina , Molineri Ana I. , Pacini Adriana , Fondevila Norberto , Pietronave Hernán , Rodríguez Graciela , Palacio Alejandra , Bulacio Cagnolo Natalia , Orellano Emanuel , Salto César E. , Signorini Marcelo L. , Merke Julieta
Published: April 2016

Honey bee colonies are threatened by multiple factors including complex interactions between environmental and diseases such as parasitic mites and viruses. We compared the presence of honeybee‐pathogenic viruses and Varroa infestation rate in four apiaries: commercial colonies that received treatment against Varroa and non‐treated colonies that did not received any treatment for the last 4 years located in temperate and subtropical climate. In addition, we evaluated the effect of climate and Varroa treatment on deformed wing virus (DWV) amounts. In both climates, DWV was the most prevalent virus, being the only present virus in subtropical colonies. Moreover, colonies from subtropical climate also showed reduced DWV amounts and lower Varroa infestation rates than colonies from temperate climate. Nevertheless, non‐treated colonies in both climate conditions are able to survive several years. Environment appears as a key factor interacting with local bee populations and influencing colony survival beyond Varroa and virus presence.
Mucosa‐attached bacterial community in Crohn's disease coheres with the clinical disease activity index
Authors: Schäffler Holger , Herlemann Daniel P. R. , Alberts Christian , Kaschitzki Annika , Bodammer Peggy , Bannert Karen , Köller Thomas , Warnke Philipp , Kreikemeyer Bernd , Lamprecht Georg
Published: April 2016

In inflammatory bowel diseases (IBD), microbial communities often become imbalanced suggesting abnormal microbial‐gut interactions. In this study, we analysed the mucosa‐attached gut microbiota from 26 Crohn's disease (CD) patients using 16S rRNA gene amplicon sequencing. The samples were stratified according to their disease activity (Crohn's disease activity index, CDAI). The different disease activity categories had a comparable bacterial richness. Bacterial communities of patients in remission and intermediate CDAI (0–220) were relatively similar and dominated by the genus Bacteroides (>40%). The bacterial composition of patients assigned to a high CDAI category was dominated by Pelomonas (25%) and Flavobacterium (13%) but had a low relative abundance of Bacteroidetes (4%). This indicates the presence of specific abundant bacterial taxa at different CDAI levels. In addition, bacterial communities were also significantly influenced when a tumour necrosis factor (TNF)‐α inhibitor was applied or by the local mucosal inflammation level. As a consequence, a shift of the microbial composition may also indicate a change of the disease activity in CD patients.
Listeria monocytogenes remodels the cell surface in the blood‐stage
Authors: Quereda Juan J. , García‐del Portillo Francisco , Pucciarelli M. Graciela
Published: April 2016

After crossing the intestinal barrier, the bacterial pathogen Listeria monocytogenes disseminates via the blood to the liver, spleen, brain and placenta. Transcriptomic studies have shown that L. monocytogenes changes expression of many genes during this blood‐stage. However, no comparable data at the protein level are known. As main interactors with the environment, we focused in surface proteins produced by L. monocytogenes in an ex vivo bovine blood model. Bacteria exposed to blood alter selectively the amount of several surface proteins compared with bacteria grown in laboratory media. Increased levels were detected for Lmo0514 and Internalin A, two surface proteins covalently bound to peptidoglycan, and the moonlighting protein alcohol‐acetaldehyde dehydrogenase, also known as Lap for ‘Listeria adhesion protein’. Lmo0514, induced by L. monocytogenes inside epithelial cells, is required for survival in plasma and for virulence in mice at early infection stages. Lmo0514 is also important to cope with low pH stress. By contrast, L. monocytogenes down‐regulates other surface proteins following exposure to blood and plasma such as Internalin I. These data provide evidence for remodelling of the L. monocytogenes cell surface during the blood‐stage, which it could facilitate pathogen dissemination to deep organs.
The association between meal timing and frequency with cardiometabolic profile in patients with bipolar disorder
Authors: Soreca I. , Wallace M. L. , Hall M. H. , Hasler B. P. , Frank E. , Kupfer D. J.
Published: April 2016

Objective

The goal of this study was to explore the association of timing of and frequency of meals with markers of cardiometabolic risk in patients with bipolar disorder in out‐patient maintenance treatment.

Methods

We used Pittsburgh Sleep Diary and actigraphy measures for individuals with bipolar I disorder. Linear and logistic regression analyses were used to determine whether dinnertime, instability of dinnertime, and/or interval between meals were associated with metabolic syndrome and its components.

Results

Later dinnertime was associated with greater waist circumference (β = 0.25, P = 0.02) after adjusting for age, sex, dinner‐to‐bed interval, and sleep duration. Longer breakfast‐to‐lunch intervals were also associated with greater waist circumferences (β =−.35, P = .002) after adjusting for age, sex, and sleep duration. Neither instability of dinnertime nor number of meals per day was associated with the metabolic syndrome or its components.

Conclusion

Weight gain is often perceived as inevitable side‐effect of medications. While patients often need to be on medication to function, a more careful lifestyle assessment with attention to social rhythms and timing of activities may be critical not only for mood stability, but also to reduce cardiovascular risk.
Ant megadiversity and its origins in arid Australia
Authors: Andersen Alan N
Published: April 2016

It is widely recognised that arid Australia (including semi‐ and seasonally arid regions) supports an extremely diverse ant fauna. However, the truly remarkable extent of its diversity is not well appreciated, even among myrmecologists, and the reasons for such diversity are poorly understood. The vast majority of ant species in arid Australia are undescribed, and I argue that a recognition of the true diversity of the fauna would re‐define the conventional understanding of global ant diversity patterns. For example,MonomoriumMayr andTetramoriumMayr are formally recognised as widespread but essentially Afrotropical genera, whereas the large majority of species actually occur in arid Australia. The Australian fauna includes many genera each with >100 arid‐adapted species, and several of these have >300 species.MelophorusLubbock is likely to have well over 1000 species, making it one of the world's richest ant genera despite being endemic to Australia. I estimate that the total size of the ant fauna of arid Australia is as much as 7500 species, which would make it rival, if not surpass, that of the Amazon basin. I argue that the phenomenal ant diversity of arid Australia is a product of its unique history of aridity and associated patterns of speciation and extinction over the past few million years. I propose that the Pleistocene glaciations that caused waves of mass extinctions throughout the northern hemisphere actually promoted speciation in Australia. Australia remained relatively warm during glacial periods, but there was massive movement of sand during these times of peak aridity, with up to 85% of the continent covered by desert dunes. This would have resulted in a highly fragmented biota confined to a very large number of isolated refugia, providing the perfect storm for speciation.
Serum lipid levels were related to socio‐demographic characteristics in a German population‐based child cohort
Authors: Dathan‐Stumpf Anne , Vogel Mandy , Rieger Kristin , Thiery Joachim , Hiemisch Andreas , Kiess Wieland
Published: April 2016

Aim

Socio‐demographic factors affect the development and lives of children and adolescents. We examined links between serum lipids and apolipoproteins and socio‐demographic factors in the Leipzig Research Centre for Civilization Diseases Child (LIFE Child) study.

Methods

The Winkler index and the Family Affluence Scale were used to define characteristics of the social status of 938 boys and 860 girls aged from birth to 19 years. We then used univariate and multivariate regression analyses to examine the socio‐demographic impact on total cholesterol, low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL), cholesterol triglycerides and apolipoproteins A1 (ApoA1) and B (ApoB).

Results

No significant influences on the Winkler index or the Family Affluence Scale were observed regarding the concentrations of serum lipids for total cholesterol or LDL cholesterol. However, and most importantly, children and adolescents with high social status and high family affluence showed significantly higher HDL cholesterol and ApoA1 levels than those with lower individual totals. A higher Winkler index was associated with significantly lower values for triglycerides and ApoB.

Conclusion

Adolescents with higher family wealth and social status showed a lower cardiovascular risk profile, as measured by the concentrations of HDL cholesterol and triglycerides as well as ApoA1 and B.
Muscle immobilization activates mitophagy and disrupts mitochondrial dynamics in mice
Authors: Kang C. , Yeo D. , Ji L. L.
Published: April 2016

Aim

Skeletal muscle atrophy following prolonged immobilization (IM) is a catabolic state characterized by increased proteolysis and functional deterioration. Previous research indicates that discord of mitochondrial homoeostasis plays a critical role in muscle atrophy. We hypothesized that muscle IM would activate the ubiquitin‐proteolysis, autophagy–lysosome (mitophagy) pathway, mitochondrial dynamics remodelling and apoptosis partially controlled by the FoxO signalling pathway.

Methods

Female FVB/N mice were randomly divided into five groups (n = 8 each): control (CON), IM with banding of one of the hindlimbs for 1, 2 and 3 weeks (1w‐, 2w‐ and 3w‐IM) and 2w‐IM followed by 1 week of remobilization (RM).

Results

Mitochondrial density and DNA copies in tibialis anterior (TA) muscle were reduced by approx. 80% (P < 0.05 for 2w‐IM; P < 0.01 for 3w‐IM), along with activation of FoxO3a, atrogin‐1 and MuRF1 following 2w‐ and 3w‐IM (P < 0.01). Protein markers of autophagy/mitophagy, such as beclin 1 (approx. 2.7‐fold; P < 0.01), LC3, ubiquitin‐binding adaptor (approx. 1.47‐fold; P < 0.01), Rheb (approx. 1.9‐fold; P < 0.05) and parkin (approx. 70%; P < 0.05), were all increased by IM and remained activated after RM, whereas BNIP3 and PINK1 levels were decreased by IM (P < 0.05), but elevated upon RM (P < 0.01). IM decreased Mfn2 expression (approx. 50%; P < 0.01) and increased Fis‐1 expression (approx. 2.4‐fold; P < 0.05). Muscle apoptosis indicator Bax/Bcl2 ratio was elevated at 2w‐ to 3w‐IM (approx. 3.7‐fold; P < 0.01), whereas caspase‐3 activity was five‐ to sixfold higher (P < 0.01) and remained threefold higher above CON (P < 0.05).

Conclusion

Our data indicate that IM‐induced mitochondrial deterioration is associated with altered protein expressions in the autophagic/mitophagic pathway, more fragmented mitochondrial network and activation of apoptosis partly under the influence of FoxO3 activation.
Heat shock transcription factor 1‐associated expression of slow myosin heavy chain in mouse soleus muscle in response to unloading with or without reloading
Authors: Yokoyama S. , Ohno Y. , Egawa T. , Yasuhara K. , Nakai A. , Sugiura T. , Ohira Y. , Yoshioka T. , Okita M. , Origuchi T. , Goto K.
Published: April 2016

Aim

The effects of heat shock transcription factor 1 (HSF1) deficiency on the fibre type composition and the expression level of nuclear factor of activated T cells (NFAT) family members (NFATc1, NFATc2, NFATc3 and NFATc4), phosphorylated glycogen synthase kinase 3α (p‐GSK3α) and p‐GSK3β, microRNA‐208b (miR‐208b), miR‐499 and slow myosin heavy chain (MyHC) mRNAs (Myh7 and Myh7b) of antigravitational soleus muscle in response to unloading with or without reloading were investigated.

Methods

HSF1‐null and wild‐type mice were subjected to continuous 2‐week hindlimb suspension followed by 2‐ or 4‐week ambulation recovery.

Results

In wild‐type mice, the relative population of slow type I fibres, the expression level of NFATc2, p‐GSK3 (α and β), miR‐208b, miR‐499 and slow MyHC mRNAs (Myh7 and Myh7b) were all decreased with hindlimb suspension, but recovered after it. Significant interactions between train and time (the relative population of slow type I fibres; P = 0.01, the expression level of NFATc2; P = 0.001, p‐GSKβ; P = 0.009, miR‐208b; P = 0.002, miR‐499; P = 0.04) suggested that these responses were suppressed in HSF1‐null mice.

Conclusion

HSF1 may be a molecule in the regulation of the expression of slow MyHC as well as miR‐208b, miR‐499, NFATc2 and p‐GSK3 (α and β) in mouse soleus muscle.
Population pharmacokinetic analysis to recommend the optimal dose of udenafil in patients with mild and moderate hepatic impairment
Authors: Kim Anhye , Lee Jongtae , Shin Donghoon , Jung Yong Jin , Bahng Mi Young , Cho Joo‐Youn , Jang In‐Jin
Published: April 2016

Aims

The aim of this study was to develop a population pharmacokinetic (PK) model of udenafil and its active metabolite, DA‐8164, in healthy subjects and patients with hepatic impairment (HI) and to estimate the optimal dosing recommendations for patients with HI.

Methods

An open label, three parallel group, age and weight matched control study was conducted in 18 volunteers, six healthy subjects (n = 6) and patients with mild (Child–Pugh class A, n = 6) and moderate HI (Child–Pugh class B, n = 6). Serial blood samples were collected for up to 72 h after a single administration of udenafil 100 mg. A population PK model was developed using non‐linear mixed effects modelling (nonmem, ver. 7.2). The simulated data from the final PK model and original data of healthy subjects were compared to identify the optimal dose for patients with HI.

Results

A two compartment model for both udenafil and DA‐8164 best described the data. Prothrombin time on metabolic clearance of udenafil to DA‐8164 was included in the final model as a covariate. Compared with the AUC(0,tlast) value after administration of udenafil 100 mg to healthy subjects, the geometric mean ratios (95% confidence interval) after 100 mg and 75 mg udenafil administration were 1.21 (1.10, 1.32) and 0.74 (0.67, 0.81) in patients with mild HI, respectively. Meanwhile, those were 1.55 (1.43, 1.67) and 1.02 (0.92, 1.12) in patients with moderate HI, respectively.

Conclusions

This study suggests that the recommended doses of udenafil are 100 mg and 75 mg in patients with mild and moderate HI, respectively.
Feasibility for active surveillance in biopsy Gleason 3 + 4 prostate cancer: an Australian radical prostatectomy cohort
Authors: Wong Lih‐Ming , Tang Vincent , Peters Justin , Costello Anthony , Corcoran Niall
Published: April 2016

Objective

To examine the feasibility of active surveillance for low volume Gleason sum (GS) 3 + 4 disease compared to GS 3 + 3 disease.

Patients and Methods

Retrospective review of 929 patients, with biopsy proven GS 3 + 3 and 3 + 4 PCa, undergoing upfront radical prostatectomy (RP) was performed. Suitability for AS was adapted from protocols by Royal Marsden Hospital, University of Toronto, and PRIAS by allowing Gleason 3 + 4 disease.

The outcomes assessed were adverse pathology at RP (upgrading ≥GS 4 + 3 and/or upstaging ≥pT3) and biochemical recurrence (BCR) after RP.

Results

Adverse pathology at RP was compared between GS 3 + 3 vs 3 + 4 groups. When selecting patients using Royal Marsden (n = 714) or University of Toronto (n = 699) protocols, there was statistically significantly more adverse pathology at RP in GS 3 + 4 group (21% vs 31%, P = 0.0028 and 19% vs 33%, P=<0.001 respectively). Using the more stringent PRIAS protocol (n = 198), there was no statistical significant difference in groups.

There was no difference in BCR survival between biopsy GS 3 + 3 and 3 + 4 groups, regardless of which AS protocol assessed. Pre‐operative PSA and clinical staging were the predictors for BCR.

Conclusion

Presence of Gleason 3 + 4 at biopsy, when compared to 3 + 3, increases the risk of adverse pathology being present at radical prostatectomy for less stringent selection criteria. When considering AS, a stricter protocol such as PRIAS, limiting PSA density and number of positive cores to ≤2, appears to decrease the risk of adverse pathology. No differences in BCR were seen between biopsy 3 + 3 and 3 + 4 disease, regardless of AS selection criteria.
Associations between chronic systemic diseases and primary open angle glaucoma: an epidemiological perspective
Authors: Tham Yih‐Chung , Cheng Ching‐Yu
Published: April 2016

Glaucoma is a leading cause of global irreversible blindness. Primary open angle glaucoma (POAG) is the most common form of glaucoma and affects 44.1 million individuals worldwide. Elevation of intraocular pressure and impairment of vascular supply to the optic nerve head are two key pathogenic processes in the development of POAG. In this regard, chronic systemic conditions such as hypertension, diabetes and obesity have been postulated to be correlated with these two pathogenic processes. Thus, it is plausible that chronic systemic diseases may act as risk factors for POAG. The aim of this review is to summarize the current evidence on the associations of chronic systemic diseases with POAG. These information will help to further ascertain the risk factors for POAG and improve the early detection of POAG.
The risk of bias of animal experiments in implant dentistry: a methodological study
Authors: Faggion Clovis Mariano , Diaz Karla Tatiana , Aranda Luisiana , Gabel Frank , Listl Stefan , Alarcón Marco Antonio
Published: April 2016

Objectives

To evaluate the risk of bias (ROB) in reports of randomised controlled trials (RCTs) of animal experiments published in implant dentistry, and to explore the association between animal experiment characteristics and ROB.

Material and methods

We searched the MEDLINE (via PubMed), SCOPUS and SciELO databases from 2010 to March 2015 for reports of RCTs of animal experiments published in implant dentistry. We evaluated independently and in duplicate the ROB of these experiments by the use of a tool specifically developed to evaluate ROB in animal studies, the SYRCLE's tool. ROB was judged as low, high or unclear (when there was not enough information to judge ROB). We used univariate and multivariate logistic regression analyses to evaluate the association of specific study characteristics and extent of ROB.

Results

We initially selected 850 publications and 161 reports of animal experiments were included. For a total of 1449 entries (records), 486 (34%) were rated as low ROB. High ROB was attributed to 80 (6%) of entries, and 883 (60%) entries were rated as unclear ROB. The characteristics “impact factor” (IF), reporting of standard error (SE) and reporting of confidence interval (CI) were significantly associated with low ROB in some SYRCLE domains.

Conclusions

A substantial number of items with unclear ROB were observed in this sample of animal experiments in implant dentistry. Furthermore, the present findings suggest that implant dentistry animal experiments published in journals with higher IF and better report of measures of precision; that is, CI and SE may have lower ROB than those not having these characteristics.
Adaptive conjoint analysis: A new approach to defining corporate governance
Authors: Adrian Christofer , Wright Sue , Kilgore Alan
Published: April 2016

Manuscript Type

Empirical

Research Question/Issue

The method introduced to the corporate governance literature by this paper captures the construct of corporate governance in a small number of attributes, using responses made by directors and shareholders to an adaptive conjoint analysis questionnaire.

Research Findings/Insights

We demonstrate how to identify the key attributes of corporate governance from directors' and shareholders' relative preferences among a set of corporate governance attributes. The dominance of CEO duality as a relatively more important attribute is a key finding.

Theoretical/Academic Implications

Adaptive conjoint analysis is a useful technique for research into governance issues characterized by constrained choice. For future researchers seeking to capture governance in a limited number of measures, we have identified four attributes considered by directors and shareholders to comprise effective corporate governance, with the single measure of CEO duality being the most important.

Practitioner/Policy Implications

This parsimonious set of attributes can guide the design of future corporate governance regulations, to avoid costly over‐regulation. We do not suggest that restrictions on multiple directorships or an appropriate board size should be added to current requirements, and the surprisingly low perceptions of audit partner tenure and audit committee size as important to good corporate governance suggest that these attributes could be excluded from future regulations.
Aortic Valve Disease and Vascular Mechanics: Two‐Dimensional Speckle Tracking Echocardiographic Analysis
Authors: Leite Luís , Teixeira Rogério , Oliveira‐Santos Manuel , Barbosa António , Martins Rui , Castro Graça , Gonçalves Lino , Pego Mariano
Published: April 2016

Purpose

Degenerative aortic valve disease (AVD) is a complex disorder that goes beyond valve itself, also undermining aortic wall. We aimed to assess the ascending aortic mechanics with two‐dimensional speckle tracking echocardiography (2DSTE) in patients with aortic regurgitation (AR) and hypothesized a relationship with degree of AR. Aortic mechanics were then compared with those of similarly studied healthy controls and patients with aortic stenosis (AS); finally, we aimed to assess the prognostic significance of vascular mechanics in AVD.

Methods

Overall, 73 patients with moderate‐to‐severe AR and 22 healthy subjects were enrolled, alongside a previously examined cohort (N = 45) with moderate‐to‐severe AS. Global circumferential ascending aortic strain (CAAS) and strain rate (CAASR) served as indices of aortic deformation; corrected CAAS was calculated as CAAS/pulse pressure (PP). Median clinical follow‐up was 438 days.

Results

In patients with severe (vs. moderate) AR, CAASR (1.53 ± 0.29/sec vs. 1.90 ± 0.62/sec, P < 0.05) and corrected CAAS (0.14 ± 0.06%/mmHg vs. 0.19 ± 0.08%/mmHg, P < 0.05) were significantly lower, whereas CAAS did not differ significantly. Measurers of aortic mechanics (CAAS, corrected CAAS, CAASR) differed significantly (all P < 0.01) in patients with AS and AR and in healthy subjects, with lower values seen in patients with AS. In follow‐up, survival rate of AVD patients with baseline CAASR >0.88/sec was significantly higher (log rank, 97.4% vs. 73.0%; P = 0.03).

Conclusions

Quantitative measures of aortic mechanics were lower for AS patients, suggesting a more significant derangement of aortic elastic properties. In the context of AVD, vascular mechanics assessment proved useful in gauging clinical prognosis.
Topical betamethasone butyrate propionate exacerbates pressure ulcers after cutaneous ischemia–reperfusion injury
Authors: Uchiyama Akihiko , Yamada Kazuya , Perera Buddhini , Ogino Sachiko , Yokoyama Yoko , Takeuchi Yuko , Ishikawa Osamu , Motegi Sei‐ichiro
Published: April 2016

Ischaemia–reperfusion (I/R) is involved in the development of various organ diseases. There has been increasing evidence that cutaneous I/R injury is associated with the pathogenesis of pressure ulcers (PUs), especially at the early stage presenting as non‐blanchable erythema. However, there is no evidence‐based treatment for early‐stage PUs. Our objective was to assess the effects of topical steroid on the development of PUs after cutaneous I/R injury in mice. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 h, followed by plate removal. Topical application of betamethasone butyrate propionate (BBP) in I/R areas significantly increased the size of PUs after I/R. The number of thromboses was increased, and CD31+ vessels were decreased in the I/R area treated with topical BBP. The number of oxidative stress‐associated DNA‐damaged cells and apoptotic cells in the I/R area was increased by topical BBP treatment. In addition, the mRNA level of NADPH oxidase 4 (Nox4), the essential enzyme that produces reactive oxygen species, was significantly increased and that of NF‐E2‐related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidant proteins, was inhibited in the I/R area treated by BBP. The number of CD68+ macrophages and the level of transforming growth factor‐beta in lesional skin were also decreased by BBP. These results suggest that a topical steroid might accelerate the formation of PUs induced by cutaneous I/R injury by aggravating oxidative stress‐induced tissue damage. Topical steroids might not be recommended for the treatment of acute‐phase decubitus ulcers.
Mania associated with ranitidine: a case report and review of literature
Authors: Mauran Audrey , Goze Tudi , Abadie Delphine , Bondon‐Guitton Emmanuelle , Chevrel Pauline , Schmitt Laurent , Montastruc Jean‐Louis , Montastruc François
Published: April 2016

H2 receptor antagonists can be associated with central adverse drug reactions (ADRs), like confusion, delirium, hallucinations, slurred speech or headaches. We report here a ‘serious’ case of severe mania leading to hospitalization in a 42‐year‐old alcohol‐dependent man, 4 days after ranitidine introduction. Review of literature showed that this ‘very rare’ ADR occurs mainly in patients with predisposing factors: age, decrease in renal and/or hepatic function, polymedication, alcohol. Knowledge of this ADR can be particularly important for these drugs widely used as self‐medication.
To eat, or NOt to eat: S‐nitrosylation signaling in autophagy
Authors: Montagna Costanza , Rizza Salvatore , Maiani Emiliano , Piredda Lucia , Filomeni Giuseppe , Cecconi Francesco
Published: April 2016

Autophagy is the main catabolic cellular process through which cells adapt their needs (e.g., growth and proliferation) to environmental availability of nutrients (e.g., amino acid and glucose) and growth factors. The rapid activation of the autophagy response essentially depends on protein post‐translational modifications (PTMs), which act as molecular switches triggering signaling cascades. Deregulation of autophagy contributes to pathological conditions, such as cancer and neurodegeneration. Therefore, understanding how PTMs affect the occurrence of autophagy is of the highest importance for clinical applications. Besides phosphorylation and ubiquitylation, which represent the best known examples of PTMs, redox‐based modifications are also emerging as contributing to the regulation of intracellular signaling. Of note, S‐nitrosylation of cysteine residues is a redox PTM and is the principal mechanism of nitric oxide‐based signaling. Results emerging in recent years suggest that NO has a role in modulating autophagy. However, the function of S‐nitrosylation in autophagy regulation remains still unveiled. By this review, we describe the upstream events regulating autophagy activation focusing on recently published evidence implying a S‐nitrosylation‐dependent regulation.
A small number of anadromous females drive reproduction in a brown trout (Salmo trutta) population in an English chalk stream
Authors: Goodwin Jill C. A. , Andrew King R. , Iwan Jones J. , Ibbotson Anton , Stevens Jamie R.
Published: April 2016

Brown trout,Salmo trutta, exhibit one of the most highly variable and polytypic life‐history strategies of all salmonids. Populations may be wholly freshwater‐resident or almost exclusively migratory (anadromous), or fish of a single population may exhibit varying proportions of the two life‐history strategies. Both anadromous and freshwater‐resident trout freely interbreed to produce fertile offspring.

We quantify maternal reproductive provisioning by anadromous and freshwater‐resident brown trout to their offspring and assess relative parental fitness (in terms of number, size and time of emergence of offspring). Newly emerged juvenile trout (fry) were sampled (n = 119) over the emergence period in March–April 2007 in a lowland English chalk stream; samples of adult trout [anadromous (6F : 12M) and freshwater‐resident (22F : 56M)], river‐resident trout parr and macroinvertebrate prey were also collected.

Using a novel combination of stable isotope analysis and microsatellite genotyping we demonstrate the overwhelming contribution of anadromous parents (both female and male) to fry production, despite the obvious presence and numerical dominance of resident adults. We unambiguously identify the maternal origins of 78% of juveniles sampled and show that maternal reproductive contribution to juvenile production in the river was higher for anadromous females (76%) than freshwater‐resident fish (2.5%). Offspring of anadromous females emerged earlier and at a larger body size than offspring of resident females. Similarly, while the relative contribution of resident males (37%) was higher than that of resident females, anadromous males sired considerably more offspring (63%) than resident males. This is the first study of its kind to accurately assess the reproductive contribution of anadromous male trout.

Overall, this study suggests that anadromous maternal traits provide offspring with an adaptive advantage and greater fitness in early ontogeny, and that a small number of anadromous females (six of 96 adults sampled) are the main drivers of reproduction in this system.
A time and motion study of junior doctor work patterns on the weekend: a potential contributor to the weekend effect?
Authors: Richardson L. C. , Lehnbom E. C. , Baysari M. T. , Walter S. R. , Day R. O. , Westbrook J. I.
Published: April 2016

Background

Patients admitted to hospital on weekends have a greater risk of mortality compared to patients admitted on weekdays. Junior medical officers (JMO) make up the majority of medical staff on weekends. No previous study has quantified JMO work patterns on weekends.

Aim

To describe and quantify JMO work patterns on weekends and compare them with patterns previously observed during the week.

Methods

Observational time and motion study of JMO working weekends using the Work Observation Method by Activity Timing (WOMBAT; Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia) software. Descriptive statistics were used to determine the proportion of total observed time spent in tasks.

Results

Weekend JMO predominately spent time in indirect care (32.0%), direct care (23.0%) and professional communication (22.1%). JMO spent 20.9% of time multitasking and were interrupted, on average, every 9 min. Weekend JMO spent significantly more time in direct care compared with weekdays (13.0%; P < 0.001) and nights (14.3%; P < 0.001). Weekend JMO spent significantly less time on breaks (8.5%), with less than 1 h in an 11‐h shift, compared with JMO during weekdays (16.4%; P = 0.004) and nights (27.6%; P = <0.001). Weekend JMO were interrupted at a higher rate (6.6/h) than on weekdays (rate ratio (RR) 2.9, 95% confidence intervals (CI) 2.6, 3.3) or nights (RR 5.1, 95% CI 4.2, 6.1). Multitasking on weekends (20.9%) was comparable to weekdays (18.9%; P = 0.19) but significantly higher than nights (6.4%; P = <0.001).

Conclusion

On weekends, JMO had few breaks, were interrupted frequently and engaged in high levels of multitasking. This pattern of JMO work could be a potential contributing factor to the weekend effect in terms of JMO abilities to respond safely and adequately to care demands.