bluuebunny/crossref_metadata_2025 huggingface dataset:
Mislocalization of phosphotransferase as a cause of mucolipidosis III αβ
Authors: van Meel Eline , Qian Yi , Kornfeld Stuart A.
Published: February 2014

Significance

Most disease-causing mutations in genes encoding enzymes impair the folding or catalytic function of the affected protein. Here we report that two missense mutations in the N-terminal cytoplasmic tail of a Golgi-localized enzyme result in the failure of the enzyme to be retained in the Golgi, with subsequent degradation in lysosomes/release from the cells. This mislocalization of catalytically active phosphotransferase represents the basis of the lysosomal storage disorder present in patients with these mutations. In addition, these findings provide a clue to the signals that retain this enzyme, and perhaps other Golgi-resident enzymes, in the Golgi complex.
Direct Aorta Ascending Approach in Transcatheter Aortic Valve Implantation
Authors: Dahle Gry , Rein Kjell-Arne
Published: February 2014

Objective

Direct aorta ascending approach [transaortic approach (TAo)] is a new access way for transcatheter aortic valve implantation (TAVI) to be used in patients with peripheral vascular disease and as an alternative to transapical approach.

Methods

Both the Edwards SAPIEN and CoreValve systems were used. Depending on the position of the ascending aorta, the relation to the sternum, the brachiocephalic vein, vein grafts, and left and right internal mammary artery grafts from previous heart surgery, either right minithoracotomy or left ministernotomy was selected. Computed tomographic scan with reconstruction was applied for this decision making. A hybrid operating room was used with echocardiographic and fluoroscopy guidance.

Results

We have done 30 procedures via the aorta ascendens. The mean age of the patients was 80 years, and 18 were men. The mean Logistic EuroSCORE of 33 reflects the comorbidities. More than half of the patients had coronary vessel disease and had undergone coronary artery bypass graft; 20% had abdominal aortic aneurysm. The mean ejection fraction was 41%, and the patients were in New York Heart Association class III to IV. The mean gradient was 50 mm Hg, and the mean valve area was 0.7 cm2. The mean valve size was 28 mm. The use of Edwards SAPIEN versus CoreValve was 50%/50%, and thoracotomy versus sternotomy was 9 versus 21. All procedures were done successfully, but one patient had a periprocedural valve-in-valve implantation. Twenty-two patients were extubated in the operation room. The patients stayed in the intensive care unit for one night. Six patients were reoperated on. One patient had a postoperative balloon aortic valvuloplasty. The overall survival was 81% (follow up, 1–18 months).

Conclusions

Access design is an important issue in TAVI. When central approach is needed, TAVI-TAo is safe. For patients with low ejection fraction, the TAVI-TAo is preferred to the TAVI-transapical. The cannulation technique of the aorta is well known for cardiothoracic surgeons, and the method is feasible both for the Medtronic CoreValve and the Edwards SAPIEN valve, either via right minithoracotomy or ministernotomy to obtain the best coaxial alignment. It seems easier to position the bigger valves more precisely via this central approach.
Defining the Role of Chest Radiography in Determining Candidacy for Pectus Excavatum Repair
Authors: Poston Patrick M. , Patel Sonali S. , Rajput Maheen , Rossi Nicholas O. , Davis James E. , Turek Joseph W.
Published: February 2014

Objective

The Haller index (HI), derived from computed tomography (CT) of the chest, remains the standard for determining pectus excavatum (PE) severity. The ability to accurately determine PE severity from chest radiography (CXR) may provide substantial benefits. This study proposes to establish data-driven criteria for the use of CXR as a diagnostic modality in the preoperative evaluation of patients with PE.

Methods

A database of 77 patients with PE receiving preoperative CXR and CT was created. Haller indices were obtained from CT scans. Two cardiothoracic surgeons, blinded to the CT HI scores, independently calculated CXR HIs. Interrater reliability, correlations, sensitivity, specificity, and accuracy were calculated.

Results

A significant correlation was found between CXR HI estimates of the two observers, r = 0.84. Computed tomography HIs were used as the standard for identifying patients meeting surgical criteria (CT HI ≥3.2). From this, sensitivities, specificities, and accuracies were calculated for the corresponding CXR HIs determined by each observer. Observer CXR HI estimates had a sensitivity of 0.94 and 0.92, specificity of 0.77 and 0.42, and accuracy of 0.88 and 0.75.

Conclusions

We found a strong correlation between HIs calculated with each modality. In addition, CXR HIs demonstrated good interrater reliability. Although the sensitivity of CXR in diagnosing severe PE (CT HI ≥3.2) was high, specificity was less convincing. However, when using a cutoff of CXR HIs of 3.75 or greater, combined specificity was quite high (0.96). We recommend replacing CT with CXR in the pre-operative evaluation for PE. Computed tomography should be used as a confirmatory test for CXR HIs between 3.2 and 3.75.
Dark-field hyperspectral X-ray imaging
Authors: Egan Christopher K. , Jacques Simon D. M. , Connolley Thomas , Wilson Matthew D. , Veale Matthew C. , Seller Paul , Cernik Robert J.
Published: February 2014

In recent times, there has been a drive to develop non-destructive X-ray imaging techniques that provide chemical or physical insight. To date, these methods have generally been limited; either requiring raster scanning of pencil beams, using narrow bandwidth radiation and/or limited to small samples. We have developed a novel full-field radiographic imaging technique that enables the entire physio-chemical state of an object to be imaged in a single snapshot. The method is sensitive to emitted and scattered radiation, using a spectral imaging detector and polychromatic hard X-radiation, making it particularly useful for studying large dense samples for materials science and engineering applications. The method and its extension to three-dimensional imaging is validated with a series of test objects and demonstrated to directly image the crystallographic preferred orientation and formed precipitates across an aluminium alloy friction stir weld section.
Genetic connectivity for two bear species at wildlife crossing structures in Banff National Park
Authors: Sawaya Michael A. , Kalinowski Steven T. , Clevenger Anthony P.
Published: February 2014

Roads can fragment and isolate wildlife populations, which will eventually decrease genetic diversity within populations. Wildlife crossing structures may counteract these impacts, but most crossings are relatively new, and there is little evidence that they facilitate gene flow. We conducted a three-year research project in Banff National Park, Alberta, to evaluate the effectiveness of wildlife crossings to provide genetic connectivity. Our main objective was to determine how the Trans-Canada Highway and crossing structures along it affect gene flow in grizzly (Ursus arctos) and black bears (Ursus americanus). We compared genetic data generated from wildlife crossings with data collected from greater bear populations. We detected a genetic discontinuity at the highway in grizzly bears but not in black bears. We assigned grizzly bears that used crossings to populations north and south of the highway, providing evidence of bidirectional gene flow and genetic admixture. Parentage tests showed that 47% of black bears and 27% of grizzly bears that used crossings successfully bred, including multiple males and females of both species. Differentiating between dispersal and gene flow is difficult, but we documented gene flow by showing migration, reproduction and genetic admixture. We conclude that wildlife crossings allow sufficient gene flow to prevent genetic isolation.
Brood parasitism: a good strategy in our changing world?
Authors: Ducatez Simon
Published: February 2014

The original life-history strategy of brood-parasitic birds has been the focus of a large number of studies in ecology and evolution. Whether species adopting such a strategy differ in their response to global changes remains, however, unknown. Both the absence of investment in parental care and the capacity to spread nesting failure by laying eggs in several nests might help brood parasites in dealing with environmental changes. Alternatively, brood parasites might cumulate the negative effects of environmental changes on their own environment and on their hosts’ environment. Here, I tested whether brood parasites’ extinction risk and population trend differed from those of species with parental care. Focusing on the five bird families containing brood parasite species, I show that brood parasites are less at risk of extinction, and have a more stable population trend than species with parental care. In addition, I found that brood parasites with a higher host diversity were more likely to be increasing than those with fewer hosts. The bet-hedging strategy of brood parasites, by allowing them to spread nesting failure risks associated with environmental changes, is likely to help them resist current global changes.
The spectral transmission of ocular media suggests ultraviolet sensitivity is widespread among mammals
Authors: Douglas R. H. , Jeffery G.
Published: February 2014

Although ultraviolet (UV) sensitivity is widespread among animals it is considered rare in mammals, being restricted to the few species that have a visual pigment maximally sensitive (λmax) below 400 nm. However, even animals without such a pigment will be UV-sensitive if they have ocular media that transmit these wavelengths, as all visual pigments absorb significant amounts of UV if the energy level is sufficient. Although it is known that lenses of diurnal sciurid rodents, tree shrews and primates prevent UV from reaching the retina, the degree of UV transmission by ocular media of most other mammals without a visual pigment withλmaxin the UV is unknown. We examined lenses of 38 mammalian species from 25 families in nine orders and observed large diversity in the degree of short-wavelength transmission. All species whose lenses removed short wavelengths had retinae specialized for high spatial resolution and relatively high cone numbers, suggesting that UV removal is primarily linked to increased acuity. Other mammals, however, such as hedgehogs, dogs, cats, ferrets and okapis had lenses transmitting significant amounts of UVA (315–400 nm), suggesting that they will be UV-sensitive even without a specific UV visual pigment.
Multifarious selection through environmental change: acidity and predator-mediated adaptive divergence in the moor frog (Rana arvalis)
Authors: Egea-Serrano Andrés , Hangartner Sandra , Laurila Anssi , Räsänen Katja
Published: February 2014

Environmental change can simultaneously cause abiotic stress and alter biological communities, yet adaptation of natural populations to co-changing environmental factors is poorly understood. We studied adaptation to acid and predator stress in six moor frog (Rana arvalis) populations along an acidification gradient, where abundance of invertebrate predators increases with increasing acidity ofR. arvalisbreeding ponds. First, we quantified divergence among the populations in anti-predator traits (behaviour and morphology) at different rearing conditions in the laboratory (factorial combinations of acid or neutral pH and the presence or the absence of a caged predator). Second, we evaluated relative fitness (survival) of the populations by exposing tadpoles from the different rearing conditions to predation by free-ranging dragonfly larvae. We found that morphological defences (relative tail depth) as well as survival of tadpoles under predation increased with increasing pond acidity (under most experimental conditions). Tail depth and larval size mediated survival differences among populations, but the contribution of trait divergence to survival was strongly dependent on prior rearing conditions. Our results indicate thatR. arvalispopulations are adapted to the elevated predator pressure in acidified ponds and emphasize the importance of multifarious selection via both direct (here: pH) and indirect (here: predators) environmental changes.
Can the Cyanobacterial Carbon-Concentrating Mechanism Increase Photosynthesis in Crop Species? A Theoretical Analysis
Authors: McGrath Justin M. , Long Stephen P.
Published: February 2014

Experimental elevation of [CO2] around C3 crops in the field has been shown to increase yields by suppressing the Rubisco oxygenase reaction and, in turn, photorespiration. Bioengineering a cyanobacterial carbon-concentrating mechanism (CCM) into C3 crop species provides a potential means of elevating [CO2] at Rubisco, thereby decreasing photorespiration and increasing photosynthetic efficiency and yield. The cyanobacterial CCM is an attractive alternative relative to other CCMs, because its features do not require anatomical changes to leaf tissue. However, the potential benefits of engineering the entire CCM into a C3 leaf are unexamined. Here, a CO2 and HCO3  − diffusion-reaction model is developed to examine how components of the cyanobacterial CCM affect leaf light-saturated CO2 uptake (A  sat) and to determine whether a different Rubisco isoform would perform better in a leaf with a cyanobacterial CCM. The results show that the addition of carboxysomes without other CCM components substantially decreases A  sat and that the best first step is the addition of HCO3  − transporters, as a single HCO3  − transporter increased modeled A  sat by 9%. Addition of all major CCM components increased A  sat from 24 to 38 µmol m−2 s−1. Several Rubisco isoforms were compared in the model, and increasing ribulose bisphosphate regeneration rate will allow for further improvements by using a Rubisco isoform adapted to high [CO2]. Results from field studies that artificially raise [CO2] suggest that this 60% increase in A  sat could result in a 36% to 60% increase in yield.
Apyrase Suppression Raises Extracellular ATP Levels and Induces Gene Expression and Cell Wall Changes Characteristic of Stress Responses
Authors: Lim Min Hui , Wu Jian , Yao Jianchao , Gallardo Ignacio F. , Dugger Jason W. , Webb Lauren J. , Huang James , Salmi Mari L. , Song Jawon , Clark Greg , Roux Stanley J.
Published: February 2014

Plant cells release ATP into their extracellular matrix as they grow, and extracellular ATP (eATP) can modulate the rate of cell growth in diverse tissues. Two closely related apyrases (APYs) in Arabidopsis (Arabidopsis thaliana), APY1 and APY2, function, in part, to control the concentration of eATP. The expression of APY1/APY2 can be inhibited by RNA interference, and this suppression leads to an increase in the concentration of eATP in the extracellular medium and severely reduces growth. To clarify how the suppression of APY1 and APY2 is linked to growth inhibition, the gene expression changes that occur in seedlings when apyrase expression is suppressed were assayed by microarray and quantitative real-time-PCR analyses. The most significant gene expression changes induced by APY suppression were in genes involved in biotic stress responses, which include those genes regulating wall composition and extensibility. These expression changes predicted specific chemical changes in the walls of mutant seedlings, and two of these changes, wall lignification and decreased methyl ester bonds, were verified by direct analyses. Taken together, the results are consistent with the hypothesis that APY1, APY2, and eATP play important roles in the signaling steps that link biotic stresses to plant defense responses and growth changes.
Additional Amphivasal Bundles in Pedicel Pith Exacerbate Central Fruit Dominance and Induce Self-Thinning of Lateral Fruitlets in Apple
Authors: Celton Jean-Marc , Dheilly Emmanuelle , Guillou Marie-Charlotte , Simonneau Fabienne , Juchaux Marjorie , Costes Evelyne , Laurens François , Renou Jean-Pierre
Published: February 2014

Apple (Malus × domestica) trees naturally produce an excess of fruitlets that negatively affect the commercial value of fruits brought to maturity and impact their capacity to develop flower buds the following season. Therefore, chemical thinning has become an important cultural practice, allowing the selective removal of unwanted fruitlets. As the public pressure to limit the use of chemical agents increases, the control of thinning becomes a major issue. Here, we characterized the self-thinning capacity of an apple hybrid genotype from the tree scale to the molecular level. Additional amphivasal vascular bundles were identified in the pith of pedicels supporting the fruitlets with the lowest abscission potential (central fruitlet), indicating that these bundles might have a role in the acquisition of dominance over lateral fruitlets. Sugar content analysis revealed that central fruitlets were better supplied in sorbitol than lateral fruitlets. Transcriptomic profiles allowed us to identify genes potentially involved in the overproduction of vascular tissues in central pedicels. In addition, histological and transcriptomic data permitted a detailed characterization of abscission zone development and the identification of key genes involved in this process. Our data confirm the major role of ethylene, auxin, and cell wall-remodeling enzymes in abscission zone formation. The shedding process in this hybrid appears to be triggered by a naturally exacerbated dominance of central fruitlets over lateral ones, brought about by an increased supply of sugars, possibly through additional amphivasal vascular bundles. The characterization of this genotype opens new perspectives for the selection of elite apple cultivars.
Melatonin and tadalafil treatment improves erectile dysfunction after spinal cord injury in rats
Authors: Tavukçu Hasan Hüseyin , Şener Tarik Emre , Tinay İlker , Akbal Cem , Erşahin Mehmet , Çevik Özge , Çadırcı Selin , Reiter Russel J , Şener Göksel
Published: February 2014

Oxidative stress plays an important role both in spinal cord injury (SCI) and erectile dysfunction (ED). The present study investigated the effects of melatonin and tadalafil treatment alone or in combination on SCI‐induced ED.

Male Wistar albino rats (n = 40) were divided into five groups: sham‐operated control and SCI‐injured rats given either vehicle, melatonin (10 mg/kg, i.p.), tadalafil (10 mg/kg, p.o.) or a combination of melatonin and tadalafil. Spinal cord injury was induced using a standard weight‐drop method. On Day 7 after SCI, intracavernosal pressure (ICP) was measured and all rats were decapitated. Cavernosal tissues were obtained to examine caspase 3, nitric oxide synthase (NOS), myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, as well as cGMP, nerve growth factor (NGF), malondialdehyde (MDA) and glutathione (GSH) levels.

Spinal cord injury caused oxidative damage, as evidenced by increases in MDA and cGMP levels. In addition, MPO and caspase 3 activites were increased after SCI, whereas GSH and NGF levels and SOD activity were reduced. Melatonin effectively reversed these oxidative changes. Furthermore, in rats treated with both melatonin and tadalafil, the recoveries were more pronounced than in rats given either melatonin or tadalafil alone. The ICP/mean arterial pressure value in vehicle‐treated SCI rats was significantly higher than in the control group, whereas in the tadalafil‐ and tadalafil + melatonin‐treated groups have returned this value had returned to control levels.

As an individual treatment, and especially when combined with tadalafil, a well‐known agent in the treatment of ED, melatonin prevented SCI‐induced oxidative damage to cavernosal tissues and restored ED, most likely due to its anti‐oxidant effects.
Dual symbiosis with co‐occurring sulfur‐oxidizing symbionts in vestimentiferan tubeworms from a Mediterranean hydrothermal vent
Authors: Zimmermann Judith , Lott Christian , Weber Miriam , Ramette Alban , Bright Monika , Dubilier Nicole , Petersen Jillian M.
Published: February 2014

Vestimentiferan Tws colonize hydrothermal vents and cold seeps worldwide. They lack a digestive system and gain nutrition from endosymbiotic sulfur‐oxidizing bacteria. It is currently assumed that vestimentiferan Tws harbour only a single endosymbiont type. A few studies found indications for additional symbionts, but conclusive evidence for a multiple symbiosis is still missing. We investigated Tws from Marsili Seamount, a hydrothermal vent in the Mediterranean Sea. Molecular and morphological analyses identified the Tws as Lamellibrachia anaximandri. 16S ribosomal RNA clone libraries revealed two distinct gammaproteobacterial phylotypes that were closely related to sequences from other Lamellibrachia symbionts. Catalysed reporter deposition fluorescence in situ hybridization with specific probes showed that these sequences are from two distinct symbionts. We also found two variants of key genes for sulfur oxidation and carbon fixation, suggesting that both symbiont types are autotrophic sulfur oxidizers. Our results therefore show that vestimentiferans can host multiple co‐occurring symbiont types. Statistical analyses of vestimentiferan symbiont diversity revealed that host genus, habitat type, water depth and geographic region together accounted for 27% of genetic diversity, but only water depth had a significant effect on its own. Phylogenetic analyses showed a clear grouping of sequences according to depth, thus confirming the important role water depth played in shaping vestimentiferan symbiont diversity.
The experience of ISLANDS in deploying system dynamics modeling as an integrated policy tool
Authors: Deenapanray Prakash N K , Bassi Andrea M
Published: February 2014

The ISLANDS project is implemented by the Indian Ocean Commission using the European Development Fund of the European Union to support the implementation of the Mauritius Strategy in beneficiary countries. This paper shares the experiences of ISLANDS in deploying system dynamics modeling in five countries in the Eastern and Southern African and Indian Ocean Region (Comoros, Madagascar, Mauritius, Seychelles and Zanzibar) for sustainable development planning. Lessons learned regarding the design and conceptualization of the project ISLANDS, including the adoption of system dynamics modeling as an integrated assessment tool for policy planning, are discussed. Although Madagascar and Zanzibar are not defined as small island developing States (SIDS) in the UN System, the lessons learned from these countries are applicable to all SIDS. The approach used by ISLANDS for technical assistance consists of nesting learning‐by‐doing, multi‐stakeholder processes, and dedicated capacity‐building in system dynamics modeling, as well as advocacy for the integrated modeling tool with decision‐makers. While island developing States are recognized for their inherent vulnerabilities to shocks, the adoption of system dynamics modeling helps to achieve policy‐induced resilience by exposing the challenges and constraints posed by the lack of reliable statistical data. Institutionalization of the tool is progressing well in the region.
Migration from atolls as climate change adaptation: Current practices, barriers and options inSolomonIslands
Authors: Birk Thomas , Rasmussen Kjeld
Published: February 2014

Adaptive strategies are important for reducing the vulnerability of atoll communities to climate change and sea level rise in both the short and long term. This paper seeks to contribute to the emerging discourse on migration as a form of adaptation to climate change based on empirical studies in the two atoll communities,ReefIslands andOntongJava, which are located in the periphery ofSolomonIslands. The paper will outline current migration patterns in the two island groups and discuss how some of this migration may contribute to adaptation to climate change and other stresses. It shows that migration currently improves access to financial and social capital, reduces pressure on natural resources and makes island communities less vulnerable to extreme weather events and other shocks — all factors that contribute positively to adaptive capacity. It also shows that there are major barriers to migration that reduce the efficacy of positive outcomes to both migrants and their home communities, including high transport costs and problems in gaining access to housing, employment and government services in urban destination areas. If it is accepted that voluntary migration may play a positive role in adaptation to climate change in exposed atoll communities, addressing some of the barriers to migration seems logical. This may be done by efforts to stimulate migrant income opportunities, by improving migrant living conditions and by improving the transport services to the islands.
Invasive host for invasive pest: when the Asiatic cherry fly (Drosophila suzukii) meets the American black cherry (Prunus serotina) in Europe
Authors: Poyet Mathilde , Eslin Patrice , Héraude Marie , Le Roux Vincent , Prévost Geneviève , Gibert Patricia , Chabrerie Olivier
Published: February 2014

The vinegar fly Drosophila suzukii Matsumara (Diptera: Drosophilidae), native to Asia, recently invaded Europe and North America. By contrast to other frugivorous Drosophila species, D. suzukii lays eggs on ripening fruits, heavily reducing fruit production. Although cultivated host plants of D. suzukii are well documented, very little is known about wild hosts in the invaded areas.

The American black cherry Prunus serotina Ehrh., a tree species native to North America, became one of the main woody forest invaders in Europe. One cause of its invasion success is the huge amount of fruit produced by P. serotina trees.

A field survey showed that P. serotina is a suitable reservoir for the development and persistence of D. suzukii populations in European natural systems (on the forest area investigated, up to 70% of all the fruits of P. serotina were infested in one of the sampling sites).

Laboratory tests demonstrated that D. suzukii prefers ripening cherries to ripe ones, therefore increasing the chance of the larvae to fully develop and reach maturity before the mesocarp of the fruit totally decays.

Infestation of P. serotina cherries could reduce the life span of fruits, as well as their attractiveness to seed consumers and dispersers, yet P. serotina could represent a suitable plant reservoir promoting D. suzukii invasion in Europe and North America.
‘Do UC the melanoma?’ Recognising the importance of different lesions displaying unevenness or having a history of change for early melanoma detection
Authors: Yagerman Sarah E , Chen Lucy , Jaimes Natalia , Dusza Stephen W , Halpern Allan C , Marghoob Ashfaq
Published: February 2014

Background/Objectives

Many melanomas are of a diameter smaller than 6 mm and may lack classical asymmetry, border irregularity and colour variegation (ABCD). The objectives of this article are to characterise the fidelity of melanomas diagnosed in a high‐risk clinic to the ABCD and to review potential methods for early clinical detection of melanoma.

Methods

All cases of primary melanoma diagnosed by one clinician at the Memorial Sloan–Kettering Cancer Center over the past 11 years were evaluated for the presence of the ABCD. The melanomas were analysed for asymmetry of contour, unevenness in distribution of colours and textures, border irregularity, number of colours present and diameter.

Results

In all, 236 melanomas were analysed. Of these, asymmetry of contour was present in 65% and 94% demonstrated unevenness in the distribution of colours and textures. The borders were regular in 12% of the melanomas and colour variegation was present in 63%. In total, 28% of the lesions were small, with a diameter less than 6 mm. This study was limited by the subjectivity of clinical lesion analysis.

Conclusion

We put forward for your consideration a new mnemonic: ‘Do UC (different, uneven, changing) the melanoma?’ This mnemonic encompasses differential, analytical and comparative cognition strategies for an enhanced early detection of melanoma.
Innate immunity drives xenobiotic-induced murine autoimmune cholangitis
Authors: Chang C-H , Chen Y-C , Yu Y-H , Tao M-H , Leung P S C , Ansari A A , Gershwin M E , Chuang Y-H
Published: February 2014

Although primary biliary cirrhosis (PBC) is considered a model autoimmune disease, it has not responded therapeutically to traditional immunosuppressive agents. In addition, PBC may recur following liver transplantation, despite the absence of major histocompatibility complex (MHC) matching, in sharp contrast to the well-known paradigm of MHC restriction. We have suggested previously that invariant natural killer T (iNK T) cells are critical to the initiation of PBC. In this study we have taken advantage of our ability to induce autoimmune cholangitis with 2-octynoic acid, a common component of cosmetics, conjugated to bovine serum albumin (2-OA–BSA), and studied the natural history of pathology in mice genetically deleted for CD4 or CD8 following immunization with 2-OA–BSA in the presence or absence of α-galactosylceramide (α-GalCer). In particular, we address whether autoimmune cholangitis can be induced in the absence of traditional CD4 and CD8 responses. We report herein that CD4 and CD8 knock-out mice immunized with 2-OA–BSA/PBS or 2-OA–BSA/α-GalCer develop anti-mitochondrial antibodies (AMAs), portal infiltrates and fibrosis. Indeed, our data suggest that the innate immunity is critical for immunopathology and that the pathology is exacerbated in the presence of α-GalCer. In conclusion, these data provide not only an explanation for the recurrence of PBC following liver transplantation in the absence of MHC compatibility, but also suggest that effective therapies for PBC must include blocking of both innate and adaptive pathways.
The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus
Authors: Schober L , Radnai D , Spratte J , Kisielewicz A , Schmitt E , Mahnke K , Fluhr H , Uhlmann L , Sohn C , Steinborn A
Published: February 2014

Physiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus (GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell (Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4+ CD127low+/− CD25+ forkhead box protein 3 (FoxP3+) Treg pool consists of four different Treg subsets: naive CD45RA+ Tregs, HLA-DR− CD45RA− memory Tregs (DR− Tregs) and the highly differentiated and activated HLA-DRlow+ CD45RA− and HLA-DRhigh+ CD45RA− memory Tregs (DRlow+ and DRhigh+ Tregs). Compared to healthy pregnancies, the percentage of CD4+ CD127low+/− CD25+ FoxP3+ Tregs within the total CD4+ T helper cell pool was not different in patients affected by GDM. However, the suppressive activity of the total CD4+ CD127low+/− CD25+ Treg pool was significantly reduced in GDM patients. The composition of the total Treg pool changed in the way that its percentage of naive CD45RA+ Tregs was decreased significantly in both patients with dietary-adjusted GDM and patients with insulin-dependent GDM. In contrast, the percentage of DR−-memory Tregs was increased significantly in patients with dietary-adjusted GDM, while the percentage of DRlow+ and DRhigh+ memory Tregs was increased significantly in patients with insulin-dependent GDM. Hence, our findings propose that alterations in homeostatic parameters related to the development and function of naive and memory Tregs may cause the reduction of the suppressive capacity of the total Treg pool in GDM patients. However, as this is an exploratory analysis, the results are only suggestive and require further validation.
Patient perceptions of the mandibular three‐implant overdenture: a practice‐based study
Authors: Emami Elham , de Souza Raphael F. , Bernier Jacques , Rompré Pierre , Feine Jocelyne S.
Published: February 2014

Objectives

Although three‐implant overdentures have often been used in clinical practice, there are few studies to support this approach. Therefore, this study aimed to determine the magnitude of change in ratings of oral health‐related quality of life and to assess patients' satisfaction ratings with mandibular three‐implant overdentures.

Materials and methods

This quasi‐experimental study examined oral health‐related quality of life and satisfaction with prosthesis in 135 edentate participants (mean age 61.6 ± 7.9 years) who received mandibular three‐implant overdentures from 2006 to 2009 in a private practice in Quebec, Canada. Data were collected from individual's dental records and a follow‐up survey. The Oral Health Impact Profile (OHIP‐20) was used to assess oral health‐related quality of life at baseline and at follow‐up. Satisfaction with the mandibular prostheses and perception of rocking movements were measured by use of a denture satisfaction questionnaire at follow‐up. Descriptive statistics, bivariate and multivariate statistical analyses were used to analyse the data.

Results

Individuals who received mandibular three‐implant overdentures had statistically significant improvements in all seven domains of the OHIP‐20 from pre‐ to post‐treatment (total OHIP change score −25.1 P < 0.001). Pre‐treatment OHIP scores and rotational movement explained 58% of the variance in the OHIP's change score (P ≤ 0.05). More than three quarters of the sample population (75.6%) were completely satisfied with their three‐implant overdentures, and 81.5% reported having no rocking movement. General satisfaction with the prostheses was not influenced by gender, type of fixture, or type of attachment.

Conclusions

The treatment of edentulism by three‐implant overdentures has favourable patient‐based outcomes, with negligible perceptions of rotational movement. However, further research is needed to compare the efficacy of this alternative to other treatment modalities, such as the two‐implant overdenture.
Low birthweight and risk of albuminuria in living kidney donors
Authors: Berglund Danielle , MacDonald David , Jackson Scott , Spong Richard , Issa Naim , Kukla Aleksandra , Reule Scott , Weber Marc , Matas Arthur J. , Ibrahim Hassan N.
Published: February 2014

Low birthweight is linked to hypertension, chronic kidney disease and even end‐stage renal disease. We hypothesized that living kidney donors born with lower birthweight may be at increased risk of hypertension, albuminuria, or reduced GFR beyond what is typical following uninephrectomy. Two hundred fifty‐seven living kidney donors who donated at the University of Minnesota between 1967 and 2005 underwent iohexol GFR and urinary albumin excretion measurements. Predictors of iohexol GFR <60 mL/min/1.73 m2, albuminuria, and hypertension were examined using logistic regression. Predictors examined include age at GFR measurement, time since donation, BMI, gender, serum creatinine level (at donation and GFR measurement), systolic and diastolic blood pressure, race, and birthweight. The latter was obtained through self‐report and verified through birth certificates and family members. Older age, higher BMI, and time from donation were associated with reduced GFR. Older age and higher BMI were also associated with hypertension. Birthweight was not associated with GFR <60 mL/min/1.73 m2: OR=0.70, 95% CI (0.28, 1.74), p = 0.45 or hypertension: OR=0.92, 95% CI (0.46, 1.84), p = 0.82 but was associated with albuminuria: OR=0.37, 95% CI (0.15, 0.92), p = 0.03. These data further strengthen the link between low birthweight and potential adverse renal outcomes.
Family Law Proceedings and the Child's Right to be Heard in Australia, the United Kingdom, New Zealand, and Canada
Authors: Fernando Michelle
Published: February 2014

This article examines the child's right to be heard in family law proceedings in four international jurisdictions, comparing laws, practices, and attitudes relating to children's participation. It critiques the methods by which children's views are heard and discusses the significant variations in each country's approach to listening to children. The article discusses each system's strengths and weaknesses in promoting children's right to be heard, reviewing international literature and highlighting recent initiatives to promote children's participation, such as the 2010 United Kingdom guidelines for judges meeting with children.

The article concludes that there is little consistency in how children's voices are heard in family law matters internationally. One possible explanation is that each jurisdiction differs in its culture of and attitude toward children's rights.

Keypoints

Children's views in family law matters

Comparative analysis of law and practice in Australia, the United Kingdom, New Zealand, and Canada

Child's right to be heard
The Effects of Judicial Personnel on Hearing and Outcome Timeliness in Juvenile Dependency Cases
Authors: Wood Steve M. , Russell Jesse R. , Macgill Stephanie O. , Summers Alicia
Published: February 2014

This article examines how the amount of judicial personnel work hours available for each juvenile dependency case in a county may be related to the percentage of cases reaching key decision hearings in a timely manner. Panel analyses of data from Washington State indicate that, when controlling for community risk factors, counties with more judicial personnel per case held timely fact‐finding and permanency planning hearings more often and more often achieved timely adoptions. Judicial personnel per case, however, was not a significant predictor of the percentage of permanent placements completed within timeliness goals.

Keypoints

Many states are not achieving the requirements of the Adoption and Safe Families Act (ASFA), leading to children languishing in care

The juvenile dependency system needs to examine ways in which it can increase the timeliness of safe and permanent placements for children

Courts are being overburdened with an increase in juvenile dependency petition filings without a corresponding increase in judicial personnel

Courts should increase their number of judicial staff, so they can process cases faster and meet outcome goals more easily
Crossing borders: Discussing the evidence relating to the mental health needs of women exposed to female genital mutilation
Authors: Mulongo Peggy , McAndrew Sue , Hollins Martin Caroline
Published: February 2014

The terms ‘Female Circumcision’ (FC), ‘FG Cutting’ (FGC) and ‘FG Mutilation’ (FGM) refer to procedures involving the partial or total removal of the external female genitalia for non‐medical reasons. In practicing countries, FGC/FC is more widely used, as it is believed to be inoffensive, providing more impartial ways of discussing the practice. Positive beliefs about FC/FGC include virginity, marriage prospects, family reputation, or passage to adulthood. Regardless of terminology, the practice exists in at least 28 African counties, and a few Asian and Middle Eastern countries. In Western society, FGM is considered a breach of human rights, being outlawed in a number of countries. With immigration trends, FGC is now prominent in Western society among practicing communities. While the past decade has seen an increase in studies and recommendations for health‐care support related to the physical health consequences of FGM, little is known about the psychological impact and its management. For many girls and women, FGC is a traumatic practice, transforming it to FGM and affecting their mental health. This discussion paper focuses on evidence relating to the mental health consequences of FGM, therapeutic interventions, and the mental health nurse's role in addressing the needs of this group of women.
Gut microbiota and liver disease
Authors: Goel Amit , Gupta Mahesh , Aggarwal Rakesh
Published: February 2014

Microbes are present in large numbers in each human being, in particularly in the gastrointestinal (GI) tract, and have long been believed to have some beneficial effects for their hosts. Till recently, however, we lacked tools for studying these organisms. Rapid technological advances in recent years have markedly improved our understanding of their role both in health and disease. Recent literature suggests that organisms in the GI tract, referred to collectively as gut microbiota, play an indispensable role in the maintenance of host's homeostasis. Alterations in the gut microbiota, that is in the nature and relative density of various constituent bacterial species, appear to have a role in pathogenesis and progression of several GI and hepatic diseases. This has also opened the vista for tinkering with gut flora in an attempt to treat or prevent such diseases. In this review, we have tried to summarize information on normal gut microbiota, laboratory techniques and animal models used to study it, and the role of its perturbations in some of the common hepatic disorders, such as non‐alcoholic fatty liver disease (including obesity), non‐alcoholic steatohepatitis, alcoholic liver disease, and liver cirrhosis and its complications.
Controlled attenuation parameter for the detection and quantification of hepatic steatosis in nonalcoholic fatty liver disease
Authors: Chan Wah‐Kheong , Nik Mustapha Nik Raihan , Mahadeva Sanjiv
Published: February 2014

Background and Aim

Controlled attenuation parameter (CAP) has been suggested as a noninvasive method for detection and quantification of hepatic steatosis. We aim to study the diagnostic performance of CAP in nonalcoholic fatty liver disease (NAFLD) patients.

Methods

Transient elastography was performed in consecutive NAFLD patients undergoing liver biopsy and non‐NAFLD controls. The accuracy of CAP for the detection and quantification of hepatic steatosis was assessed based on histological findings according to the Nonalcoholic Steatohepatitis Clinical Research Network Scoring System.

Results

Data for 101 NAFLD patients (mean age 50.3 ± 11.3 years old, 51.5% male) and 60 non‐NAFLD controls were analyzed. CAP was associated with steatosis grade (odds ratio [OR] = 29.16, P < 0.001), body mass index (BMI; OR = 4.34, P < 0.001) and serum triglyceride (OR = 13.59, P = 0.037) on multivariate analysis. The median CAP for steatosis grades S0, S1, S2, and S3 were 184 dB/m, 305 dB/m, 320 dB/m, and 324 dB/m, respectively. The areas under receiver operating characteristics curves (AUROC) for estimation of steatosis grades ≥ S1, S2, and S3 were 0.97, 0.86, and 0.75, respectively. The optimal CAP cutoffs for estimation of steatosis grades ≥ S1, S2, and S3 were 263 dB/m, 281 dB/m, and 283 dB/m, respectively. Among non‐obese patients, the AUROC for estimation of steatosis grades ≥ S1 and S2 were 0.99 and 0.99, respectively. Among obese patients, the AUROC for estimation of steatosis grades ≥ S1, S2, and S3 were 0.92, 0.64, and 0.58, respectively.

Conclusions

CAP is excellent for the detection of significant hepatic steatosis. However, its accuracy is impaired by an increased BMI, and it is less accurate to distinguish between the different grades of hepatic steatosis.
Analgesia for the cirrhotic patient: A literature review and recommendations
Authors: Dwyer Jeremy P , Jayasekera Chatura , Nicoll Amanda
Published: February 2014

The choice of analgesic agent in cirrhotic patients is problematic and must be individualized taking into account several factors including severity of liver disease, history of opioid dependence, and potential drug interactions. With a cautious approach including slow dose up‐titration and careful monitoring, effective analgesia can be achieved in most cirrhotic patients without significant side effects or decompensation of their liver disease. Paracetamol is safe in patients with chronic liver disease but reduced doses of 2–3 grams daily is recommended for long‐term use. Non‐steroidal anti‐inflammatory drugs are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Opioids have an increased risk of toxicity particularly in patients with hypoalbuminaemia, and immediate‐release as opposed to controlled‐release formulations are advised. Co‐prescription of laxatives is mandatory to avoid constipation and encephalopathy. Adjuvant analgesics such as tricyclic antidepressants and anti‐convulsants may be used cautiously for cirrhotic patients with neuropathic pain. Gabapentin or pregabalin may be better tolerated in cirrhosis because of non‐hepatic metabolism and a lack of anti‐cholinergic side effects.
Osteopontin splice variant as a potential marker for metastatic disease in pancreatic adenocarcinoma
Authors: Siddiqui Ali A , Jones Elizabeth , Andrade Darren , Shah Apeksha , Kowalski Thomas E , Loren David E , Chipitsyna Galina , Arafat Hwyda A
Published: February 2014

Background and Aim

Osteopontin (OPN) is a phosphoprotein that activates pathways that induce cancer cell survival and metastasis. Our aim was to examine the expression pattern of OPN splice variants a, b, and c in fine‐needle aspirates and to determine their correlation with stage‐adjusted pancreatic ductal adenocarcinoma (PDA) survival.

Methods

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) was performed in patients with solid pancreatic masses. The tissue was collected and analyzed for the expression of OPN isoforms by reverse transcription–polymerase chain reaction. Survival curves of stages and overexpression of OPN splice variants (a, b, c) were estimated according to the Kaplan–Meier and the log‐rank test.

Results

EUS‐FNA was performed in 46 patients with solid pancreatic lesions (40 PDA and 6 chronic pancreatitis). OPNa was highly expressed in 39/40 (98%), OPNb in 24/40 (60%), while OPNc was present in 10/40 (25%) of PDA samples. The median survival was lower in patients whose fine‐needle aspiration (FNA) samples expressed OPNb than those without (406 days vs 749 days, P = 0.049). There was no significant difference in survival in patients with OPNc. Cox proportional hazard model demonstrated that OPNb expression had a trend toward decrease overall survival (P = 0.06), with these patients having a hazard of death three times higher than those without. OPNc was found to significantly correlate with metastatic disease (P = 0.009) in PDA patients.

Conclusions

Our data show for the first time that in FNA samples, there is a strong association between OPNc and presence of metastasis in PDA, and OPNb and poor survival.
Determinants of a regular intake of a nutritionally balanced school lunch among 10–17‐year‐old schoolchildren with special reference to sense of coherence
Authors: Tilles‐Tirkkonen T. , Suominen S. , Liukkonen J. , Poutanen K. , Karhunen L.
Published: February 2014

Background

Free nutritionally balanced school lunches are offered to all schoolchildren in basic education in Finland in each school day. Having school lunch on a regular basis has been found to reflect overall eating patterns. However, skipping part of or even the entire lunch is common. The present study investigated the determinants of the regular consumption of a nutritionally balanced school lunch among schoolchildren, with special reference to the role of sense of coherence (SOC).

Methods

In total, 887 children (457 girls and 424 boys), aged 10–17 years from three municipalities in Eastern Finland, filled in a web‐based questionnaire in class during a school day and reported eating patterns, body height and weight and perception of body image. SOC was measured by using the 13‐item scale. The statistical analysis was carried out with logistic regression modelling and the chi‐squared test.

Results

In addition to female gender, frequent shared family meals, perception of body image as appropriate and younger age, SOC was a significant determinant of regularly eating a nutritionally balanced school lunch in the final multivariate modelling. Strong SOC was also associated with more regular meal frequency and health‐promoting snack choices.

Conclusions

To promote healthy eating patterns among school‐aged children, special attention should be paid to children with weak SOC because they may need specific support and encouragement. They might lack sufficient belief in their own capability and/or do not have adequate support from their family to influence their eating and other lifestyle patterns.