bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing false positive diagnoses in mild cognitive impairment: the importance of comprehensive neuropsychological assessment
Authors: Klekociuk S. Z. , Summers J. J. , Vickers J. C. , Summers M. J.
Published: June 2014

Background and purpose

Longitudinal studies of mild cognitive impairment (MCI) report that a sizeable proportion of MCI cases revert to normal levels of functioning over time. The rate of recovery from MCI indicates that existing MCI diagnostic criteria result in an unacceptably high rate of false positive diagnoses and lack adequate sensitivity and specificity.

Methods

The aim of the present study was to identify a set of neuropsychological measures able to differentiate between true positive cases of MCI from those who were unimpaired at 11 months’ follow‐up.

Results

A discriminant function analysis identified that a combination of measures of complex sustained attention, semantic memory, working memory, episodic memory and selective attention correctly classified outcome in more than 80% of cases. The rate of false positive diagnoses (5.93%) was considerably lower than is evident in previously published MCI studies.

Conclusions

The results of the present study indicate that the rate of false positive MCI diagnoses can be significantly reduced through the use of sensitive and specific neuropsychological measures of memory and non‐memory functions.
Profession Differences in Family Focused Practice in the Adult Mental Health System
Authors: Maybery Darryl , Goodyear Melinda , O'Hanlon Brendan , Cuff Rose , Reupert Andrea
Published: June 2014

There is a large gulf between what psychiatric services should (or could) provide and what they do in practice. This article sought to determine practice differences between the differing professions working in adult mental health services in terms of their family focused work. Three hundred and seven adult mental health professionals completed a cross‐sectional survey of family focused practices in adult mental health services. Findings highlight that social workers engaged in more family focused practice compared to psychiatric nurses, who performed consistently the lowest on direct family care, compared to both social workers and psychologists. Clear skill, knowledge, and confidence differences are indicated between the professions. The article concludes by offering direction for future profession education and training in family focused practices.
Critique and Sacrifice: Benjamin–Kommerell
Authors: Goebel Eckart
Published: June 2014

The essay provides a close reading of Walter Benjamin's review Wider ein Meisterwerk, which is a stylistic and philosophical masterpiece itself. I trace some of the numerous allusions to the heritage of German poetry and prose from Goethe to George via Jean Paul that Benjamin weaves into his text in order to testify to his loving closeness to German literature and, at the same time, his uncompromising distance to fascist German ideology. Benjamin deciphers Max Kommerell's Habilitationsschrift on Der Dichter als Führer in der deutschen Klassik as a failed attempt to stabilize charismatic leadership. Benjamin's meticulous reconstruction of Kommerell's art of physiognomic portraiture and proto‐constructivist reinvention of German (literary) history shows not only his indebtedness to the George Circle but also his farewell to its seductive powers: Kommerell's myth falls prey to blood and soil, while Benjamin sacrifices the German myth on the altar of the dialectic of enlightenment.
Porcelain
Authors: Schestag Thomas
Published: June 2014

Walter Benjamin developed the first piece of Berliner Kindheit um Neunzehnhundert, “Die Mummerehlen,” from a series of notes written in 1932 under the title “Zur ‘Lampe,’” from which the first draft of his later theory of reading, the “Lehre vom Ähnlichen,” also emerged. These notes are concerned, like “Die Mummerehlen,” with a single question: “What do I hear?” The word “Porzellan” shifts the first prose piece from Berliner Kindheit into the (unheard of) midst of an answer (when I bring the “Lampe” closer to my ears). In the name of similarity to the word, no less than to the matter mummed in this word (of words), Benjamin signs “Die Mummerehlen”: “Ich ähnelte dem Porzellan, in das ich mit einer Farbenwolke Einzug hielt.” In the one—shattered—word, “Porzellan,” Benjamin condenses a theory of (the language of) sex, whose epitome lies in cuts, in the pleasure in cuts, which open everything that seems to have heard, hearkened to and from, and thus to have become still and ceased to obey and to belong, to the unearthed and unheard of layers in listening. They strike the ear no less than sex.
Destruction of the hepatocyte junction by intercellular invasion of Leptospira causes jaundice in a hamster model of Weil's disease
Authors: Miyahara Satoshi , Saito Mitsumasa , Kanemaru Takaaki , Villanueva Sharon Y. A. M. , Gloriani Nina G. , Yoshida Shin‐ichi
Published: June 2014

Weil's disease, the most severe form of leptospirosis, is characterized by jaundice, haemorrhage and renal failure. The mechanisms of jaundice caused by pathogenic Leptospira remain unclear. We therefore aimed to elucidate the mechanisms by integrating histopathological changes with serum biochemical abnormalities during the development of jaundice in a hamster model of Weil's disease. In this work, we obtained three‐dimensional images of infected hamster livers using scanning electron microscope together with freeze‐cracking and cross‐cutting methods for sample preparation. The images displayed the corkscrew‐shaped bacteria, which infiltrated the Disse's space, migrated between hepatocytes, detached the intercellular junctions and disrupted the bile canaliculi. Destruction of bile canaliculi coincided with the elevation of conjugated bilirubin, aspartate transaminase and alkaline phosphatase levels in serum, whereas serum alanine transaminase and γ‐glutamyl transpeptidase levels increased slightly, but not significantly. We also found in ex vivo experiments that pathogenic, but not non‐pathogenic leptospires, tend to adhere to the perijunctional region of hepatocyte couplets isolated from hamsters and initiate invasion of the intercellular junction within 1 h after co‐incubation. Our results suggest that pathogenic leptospires invade the intercellular junctions of host hepatocytes, and this invasion contributes in the disruption of the junction. Subsequently, bile leaks from bile canaliculi and jaundice occurs immediately. Our findings revealed not only a novel pathogenicity of leptospires, but also a novel mechanism of jaundice induced by bacterial infection.
B cells as a critical node in the microbiota–host immune system network
Authors: Slack Emma , Balmer Maria L. , Macpherson Andrew J.
Published: June 2014

Mutualism with our intestinal microbiota is a prerequisite for healthy existence. This requires physical separation of the majority of the microbiota from the host (by secreted antimicrobials, mucus, and the intestinal epithelium) and active immune control of the low numbers of microbes that overcome these physical and chemical barriers, even in healthy individuals. In this review, we address how B‐cell responses to members of the intestinal microbiota form a robust network with mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut‐associated lymphoid tissues to maintain host–microbiota mutualism.
Microbiota activation and regulation of innate and adaptive immunity
Authors: Alexander Katie L. , Targan Stephan R. , Elson Charles O.
Published: June 2014

The human host has coevolved with the collective of bacteria species, termed microbiota, in a complex fashion that affects both innate and adaptive immunity. Differential regulation of regulatory T‐cell and effector T‐cell responses are a direct result of specific microbial species present within the gut, and this relationship is subject to dysregulation during inflammation and disease. The microbiota varies widely between individuals and has a profound effect on how one reacts to various environmental stimuli, particularly if a person is genetically predisposed to an immune‐mediated inflammatory disorder such as inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Approximately, half of all CD patients have elevated antibodies to CBir1, a microbiota flagellin common to mice and humans, demonstrating flagellins as immunodominant antigens in the intestines. This review focuses on the use of flagellins as probes to study microbiota‐specific responses in the context of health and disease as well as probes of innate and adaptive responses employed by the host to deal with the overwhelming bacterial presence of the microbiota.
Dendritic cell–epithelial cell crosstalk in the gut
Authors: Rescigno Maria
Published: June 2014

Intestinal epithelial cells are fundamental to maintain barrier integrity and to participate in food degradation and absorption, but they can also decipher signals coming from the outside world and ‘educate’ the immune system accordingly. In particular, they interact with dendritic cells (DCs) and other intraepithelial immune cells to drive tolerogenic responses under steady state, but they can also release immune mediators to recruit inflammatory cells and to elicit immunity to infectious agents. When these interactions are deregulated, immune disorders can develop. In this review, we discuss some important features of epithelial cells and DCs and their fruitful interactions.
The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system
Authors: Pelaseyed Thaher , Bergström Joakim H. , Gustafsson Jenny K. , Ermund Anna , Birchenough George M. H. , Schütte André , van der Post Sjoerd , Svensson Frida , Rodríguez‐Piñeiro Ana M. , Nyström Elisabeth E. L. , Wising Catharina , Johansson Malin E. V. , Hansson Gunnar C.
Published: June 2014

The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel‐forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate‐keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103+ type. In addition to the gel‐forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy.
Directing traffic: IL‐17 and IL‐22 coordinate pulmonary immune defense
Authors: McAleer Jeremy P. , Kolls Jay K.
Published: June 2014

Respiratory infections and diseases are among the leading causes of death worldwide, and effective treatments probably require manipulating the inflammatory response to pathogenic microbes or allergens. Here, we review mechanisms controlling the production and functions of interleukin‐17 (IL‐17) and IL‐22, cytokines that direct several aspects of lung immunity. Innate lymphocytes (γδ T cells, natural killer cells, innate lymphoid cells) are the major source of IL‐17 and IL‐22 during acute infections, while CD4+ T‐helper 17 (Th17) cells contribute to vaccine‐induced immunity. The characterization of dendritic cell (DC) subsets has revealed their central roles in T‐cell activation. CD11b+ DCs stimulated with bacteria or fungi secrete IL‐1β and IL‐23, potent inducers of IL‐17 and IL‐22. On the other hand, recognition of viruses by plasmacytoid DCs inhibits IL‐1β and IL‐23 release, increasing susceptibility to bacterial superinfections. IL‐17 and IL‐22 primarily act on the lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants. Recent studies found that stimulation of macrophages and DCs with IL‐17 also contributes to antibacterial immunity, while IL‐22 promotes epithelial proliferation and repair following injury. Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL‐17 and IL‐22 responses directed against innocuous antigens. Future studies will evaluate the therapeutic efficacy of targeting the IL‐17/IL‐22 pathway in pulmonary inflammation.
Anatomical localization of commensal bacteria in immune cell homeostasis and disease
Authors: Fung Thomas C. , Artis David , Sonnenberg Gregory F.
Published: June 2014

The mammalian gastrointestinal (GI) tract is colonized by trillions of beneficial commensal bacteria that are essential for promoting normal intestinal physiology. While the majority of commensal bacteria are found in the intestinal lumen, many species have also adapted to colonize different anatomical locations in the intestine, including the surface of intestinal epithelial cells (IECs) and the interior of gut‐associated lymphoid tissues. These distinct tissue localization patterns permit unique interactions with the mammalian immune system and collectively influence intestinal immune cell homeostasis. Conversely, dysregulated localization of commensal bacteria can lead to inappropriate activation of the immune system and is associated with numerous chronic infectious, inflammatory, and metabolic diseases. Therefore, regulatory mechanisms that control proper anatomical containment of commensal bacteria are essential to maintain tissue homeostasis and limit pathology. In this review, we propose that commensal bacteria associated with the mammalian GI tract can be anatomically defined as (i) luminal, (ii) epithelial‐associated, or (iii) lymphoid tissue‐resident, and we discuss the role and regulation of these microbial populations in health and disease.
Intestinal IgA production and its role in host‐microbe interaction
Authors: Gutzeit Cindy , Magri Giuliana , Cerutti Andrea
Published: June 2014

Complex and diverse communities of bacteria establish mutualistic and symbiotic relationships with the gut after birth. The intestinal immune system responds to bacterial colonization by acquiring a state of hypo‐responsiveness against commensals and active readiness against pathogens. The resulting homeostatic balance involves a continuous dialog between the microbiota and lymphocytes with the intermediation of epithelial and dendritic cells. This dialog causes massive production of immunoglobulin A (IgA), a non‐inflammatory antibody specialized in mucosal protection. Here, we discuss recent advances on the regulation of intestinal IgA responses and their role in host‐microbe interaction.
Maturation of the enteric mucosal innate immune system during the postnatal period
Authors: Fulde Marcus , Hornef Mathias W.
Published: June 2014

The innate immune system instructs the host on microbial exposure and infection. This information is critical to mount a protective innate and adaptive host response to microbial challenge, but is also involved in homeostatic and adaptive processes that adjust the organism to meet environmental requirements. This is of particular importance for the neonatal host during the transition from the protected fetal life to the intense and dynamic postnatal interaction with commensal and pathogenic microorganisms. Here, we discuss both adaptive and developmental mechanisms of the mucosal innate immune system that prevent inappropriate stimulation and facilitate establishment of a stable homeostatic host–microbial interaction after birth.
IL‐15: a central regulator of celiac disease immunopathology
Authors: Abadie Valérie , Jabri Bana
Published: June 2014

Interleukin‐15 (IL‐15) exerts many biological functions essential for the maintenance and function of multiple cell types. Although its expression is tightly regulated, IL‐15 upregulation has been reported in many organ‐specific autoimmune disorders. In celiac disease, an intestinal inflammatory disorder driven by gluten exposure, the upregulation of IL‐15 expression in the intestinal mucosa has become a hallmark of the disease. Interestingly, because it is overexpressed both in the gut epithelium and in the lamina propria, IL‐15 acts on distinct cell types and impacts distinct immune components and pathways to disrupt intestinal immune homeostasis. In this article, we review our current knowledge of the multifaceted roles of IL‐15 with regard to the main immunological processes involved in the pathogenesis of celiac disease.
Intestinal dendritic cells in the regulation of mucosal immunity
Authors: Bekiaris Vasileios , Persson Emma K. , Agace William W.
Published: June 2014

The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial‐derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut‐associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal‐draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune‐mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines.
The role of type I interferons in intestinal infection, homeostasis, and inflammation
Authors: Cho Hyeseon , Kelsall Brian L.
Published: June 2014

Type I interferons are a widely expressed family of effector cytokines that promote innate antiviral and antibacterial immunity. Paradoxically, they can also suppress immune responses by driving production of anti‐inflammatory cytokines, and dysregulation of these cytokines can contribute to host‐mediated immunopathology and disease progression. Recent studies describe their anti‐inflammatory role in intestinal inflammation and the locus containing IFNAR, a heterodimeric receptor for the type I interferons has been identified as a susceptibility region for human inflammatory bowel disease. This review focuses on the role of type I IFNs in the intestine in health and disease and their emerging role as immune modulators. Clear understanding of type I IFN‐mediated immune responses may provide avenues for fine‐tuning existing IFN treatment for infection and intestinal inflammation.
How irritant is water? An overview
Authors: Tsai Tsen‐Fang , Maibach Howard I.
Published: June 2014

Water is a skin irritant which deserves attention because of its ubiqujty. During the Vietnam war, soldiers suffered from painful swollen feet, so‐called tropical immersion foot. In occupational dermatology, the importance of water as a skin irritant is especially appreciated. The irritancy of water has been demonstrated by occlusion experiments; occlusion with either closed chambers or water‐soaked patches has been shown to produce clinical and histopathological inflammation. Functional damage, as revealed by increased transepidermal water loss, bas also been shown. Repeated water exposure without occlusion caused an increase in blood flow on irritated skin; however, clinical evaluation did not show a difference in dryness or scaling. Several mechanisms such as osmolarity, pH, hardness and temperature might account for the irritancy of water. Extraction or dilution of natural moisturizing factors in the stratum corneum is another po sible explanation. Occlusion per se also changes the physiology of skin and may trigger the activation of potentially active substances. However, much remains to be done to clarify the risk factors and mechanisms of water‐induced irritation.
Sequence diversity and molecular evolutionary rates between buffalo and cattle
Authors: Moaeen‐ud‐Din M. , Bilal G.
Published: June 2014

Identification of genes of importance regarding production traits in buffalo is impaired by a paucity of genomic resources. Choice to fill this gap is to exploit data available for cow. The cross‐species application of comparative genomics tools is potential gear to investigate the buffalo genome. However, this is dependent on nucleotide sequences similarity. In this study, gene diversity between buffalo and cattle was determined using 86 gene orthologues. There was approximately 3% difference in all genes in terms of nucleotide diversity and 0.267 ± 0.134 in amino acids, indicating the possibility for successfully using cross‐species strategies for genomic studies. There were significantly higher non‐synonymous substitutions both in cattle and buffalo; however, there was similar difference in terms of dN– dS (4.414 versus 4.745) in buffalo and cattle, respectively. Higher rate of non‐synonymous substitutions at similar level in buffalo and cattle indicated a similar positive selection pressure. Results for relative rate test were assessed with the chi‐squared test. There was no significance difference on unique mutations between cattle and buffalo lineages at synonymous sites. However, there was a significance difference on unique mutations for non‐synonymous sites, indicating ongoing mutagenic process that generates substitutional mutation at approximately the same rate at silent sites. Moreover, despite of common ancestry, our results indicate a different divergent time among genes of cattle and buffalo. This is the first demonstration that variable rates of molecular evolution may be present within the family Bovidae.
Combination of CD34‐positive cell subsets with infarcted myocardium‐like matrix stiffness: a potential solution to cell‐based cardiac repair
Authors: Zhang Shuning , Ma Xin , Yao Kang , Zhu Hong , Huang Zheyong , Shen Li , Qian Juying , Zou Yunzeng , Sun Aijun , Ge Junbo
Published: June 2014

Detection of the optimal cell transplantation strategy for myocardial infarction (MI) has attracted a great deal of attention. Commitment of engrafted cells to angiogenesis within damaged myocardium is regarded as one of the major targets in cell‐based cardiac repair. Bone marrow–derived CD34‐positive cells, a well‐characterized population of stem cells, might represent highly functional endothelial progenitor cells and result in the formation of new blood vessels. Recently, physical microenvironment (extracellular matrix stiffness) around the engrafted cells was found to exert an essential impact on their fate. Stem cells are able to feel and respond to the tissue‐like matrix stiffness to commit to a relevant lineage. Notably, the infarct area after MI experiences a time‐dependent stiffness change from flexible to rigid. Our previous observations demonstrated myocardial stiffness‐dependent differentiation of the unselected bone marrow–derived mononuclear cells (BMMNCs) along endothelial lineage cells. Myocardial stiffness (~42 kPa) within the optimal time domain of cell engraftment (at week 1 to 2) after MI provided a more favourable physical microenvironment for cell specification and cell‐based cardiac repair. However, the difference in tissue stiffness‐dependent cell differentiation between the specific cell subsets expressing and no expressing CD34 phenotype remains uncertain. We presumed that CD34‐positive cell subsets facilitated angiogenesis and subsequently resulted in cardiac repair under induction of infarcted myocardium‐like matrix stiffness compared with CD34‐negative cells. If the hypothesis were true, it would contribute greatly to detect the optimal cell subsets for cell therapy and to establish an optimized therapy strategy for cell‐based cardiac repair.
Riverine and near coastal migration performance of hatchery brown trout Salmo trutta
Authors: Davidsen J. G. , Daverdin M. , Arnekleiv J. V. , Rønning L. , Sjursen A. D. , Koksvik J. I.
Published: June 2014

To study migration performance and return rates of hatchery brown trout Salmo trutta smolts the first 5 months after release, 50 fish in each year (fork length, LF, 158–288 mm) were in two subsequent years tagged with acoustic transmitters and recorded by automatic listening stations in the River Nidelva (central Norway), its estuary and in the marine environment. More than half of the smolts became anadromous migrants (52% in 2011 and 70% in 2012). The fish spent longer time in the estuary than in the marine environment and the results suggest that migratory behaviour of S. trutta smolts is not only restricted to be resident or anadrome–lacustrine, but that there is also an intermediary strategy of estuarine feeding. There were no differences in LF or mass between groups of smolts with different migration patterns. Return rates from the sea within the first 5 months after release were in both years 16%. Median progression rate in the river was 0·090 LF s−1 but decreased significantly as the smolts entered the estuary (0·015 LF s−1). The long residential time in the estuary may increase the risk of negative effects of anthropogenic activities in estuaries, such as harbours and industrial development, and special attention should be given to evaluate effects of such activities.
Critical Appraisal of Life Cycle Impact Assessment Databases for Agri‐food Materials
Authors: Teixeira Ricardo F.M.
Published: June 2014

Simplified life cycle assessment (LCA) is an attempt to expedite standard LCA methodology. One common simplification is to use secondary databases comprised of results, instead of inventories, from previous LCA studies to avoid data collection and speed up calculations. This article contains an assessment of the depth and variance in such databases, using descriptive analyses and clustering of 2,276 published global warming potential weighted emissions records for agri‐food products. Tables with mean and standard deviation for each product were generated and can be used in the future by LCA practitioners. The analysis of the data sets shows that clustering emissions by product name explains 55% of the variance in the database, whereas geographic region and method of production of the material explain only 2%. Significant gaps in the richness and comprehensiveness of databases available are also identified; data unavailability is one of the main reasons for uncertainty. The conclusion is thus that the use of secondary databases looks promising, but there are still challenges to overcome regarding the depth of databases.
Dynamic Models of Fixed Capital Stocks and Their Application in Industrial Ecology
Authors: Pauliuk Stefan , Wood Richard , Hertwich Edgar G.
Published: June 2014

Industrial assets or fixed capital stocks are at the core of the transition to a low‐carbon economy. They represent substantial accumulations of capital, bulk materials, and critical metals. Their lifetime determines the potential for material recycling and how fast they can be replaced by new, more efficient facilities. Their efficiency determines the coupling between useful output and energy and material throughput. A sound understanding of the economic and physical properties of fixed capital stocks is essential to anticipating the long‐term environmental and economic consequences of the new energy future. We identify substantial overlap in the way stocks are modeled in national accounting, dynamic material flow analysis, dynamic input‐output (I/O) analysis, and life cycle assessment (LCA) and we merge these concepts into a common framework for modeling fixed capital stocks. We demonstrate the usefulness of the framework for simultaneous accounting of capital and material stocks and for consequential LCA. We apply the framework to design a demand‐driven dynamic I/O model with dynamic capital stocks, and we synthesize both the marginal and attributional matrix of technical coefficients (A‐matrix) from detailed process inventories of fixed assets of different age cohorts and technologies. The stock modeling framework allows researchers to identify and exploit synergies between different model families under the umbrella of socioeconomic metabolism.
Hippocampal Surface Deformation Accuracy in T1‐Weighted Volumetric MRI Sequences in Subjects with Epilepsy
Authors: Hogan R. Edward , Moseley Emily D. , Maccotta Luigi
Published: June 2014

BACKGROUND AND PURPOSE

To demonstrate the accuracy across different acquisition and analysis methods, we evaluated the variability in hippocampal volumetric and surface displacement measurements resulting from two different MRI (magnetic resonance imaging) acquisition protocols.

METHODS

Nine epilepsy patients underwent two independent T1‐weighted magnetization prepared spoiled gradient sequences during a single 3T MRI session. Using high‐dimension mapping‐large deformation (HDM‐LD) segmentation, we calculated volumetric estimates and generated a vector‐based 3‐dimensional surface model of each subject's hippocampi, and evaluated volume and surface changes, the latter using a cluster‐based noise estimation model.

RESULTS

Mean hippocampal volumes and standard deviations for the left hippocampi were 2,750 (826) mm3 and 2,782 (859) mm3 (P = .13), and for the right hippocampi were 2,558 (750) mm3 and 2,547 (692) mm3 (P = .76), respectively for the MPR1 and MPR2 sequences. Average Dice coefficient comparing overlap for segmentations was 86%. There was no significant effect of MRI sequence on volume estimates and no significant hippocampal surface change between sequences.

CONCLUSION

Statistical comparison of hippocampal volumes and statistically thresholded HDM‐LD surfaces in TLE patients showed no differences between the segmentations obtained in the two MRI acquisition sequences. This validates the robustness across MRI sequences of the HDM‐LD technique for estimating volume and surface changes in subjects with epilepsy.
Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble carriers: phase equilibria, solid-state characterisation and in-vivo/pharmacodynamic evaluation
Authors: Abdelkader Hamdy , Abdallah Ossama Y , Salem Hesham , Alani Adam W G , Alany Raid G
Published: June 2014

Objectives

The solid-state interactions of fused mixtures nimesulide (ND) with polyethylene glycol (PEG) 4000, urea or mannitol were studied through constructing thaw-melt phase equilibrium diagrams.

Methods

The solid-state characteristics were investigated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Various types of interactions were identified such as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND-urea and complete solid immiscibility of ND with mannitol. The effects of carrier concentrations on the equilibrium solubility and in-vitro dissolution characteristics were studied.

Key findings

Linear increases (R2 > 0.99) in the aqueous solubility of ND in various concentrations of PEG 4000 and urea were obtained, whereas mannitol did not exhibit any effect on the solubility of ND. Similar trends were obtained with the dissolution efficiency of the fused mixtures of ND with PEG 4000 and urea compared with the corresponding physical mixtures and untreated drug. The analgesic effects of untreated ND and the selected formulations were investigated by evaluating the drug's ability to inhibit the acetic acid-induced writhing response.

Conclusions

The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug.
Identification of human cytochrome P450 isozymes involved in the metabolism of naftopidil enantiomers in vitro
Authors: Zhu Lijun , Liu Xiawen , Zhu Liu , Zhang Xingfei , Fu Xiaojing , Huang Junjun , Yuan Mu
Published: June 2014

Objectives

Naftopidil (NAF) is a chiral compound with two enantiomers (R(+)-NAF and S(−)-NAF) and is used as a racemic mixture in clinical practice. This study aims to investigate the metabolism of NAF enantiomers in pooled human liver microsomes (HLMs) and cytochrome P450 isozymes (CYPs) involved in their metabolism.

Methods

Metabolism studies were conducted in vitro using HLMs. Specific chemical inhibitors and recombinant human CYPs were used to confirm that the CYPs contributed to the metabolism of NAF enantiomers.

Key findings

Three metabolites were found and characterized in the HLMs incubations from R(+)-NAF and S(−)-NAF, respectively. The major metabolic pathways of R(+)-NAF and S(−)-NAF were demethylation and hydroxylation. CYP2C9 and CYP2C19 inhibitors strongly inhibited R(+)-NAF metabolism, and CYP1A2, CYP2C8, CYP2D6 and CYP3A4/5 inhibitors moderately inhibited R(+)-NAF metabolism. CYP2C9 inhibitors strongly inhibited S(−)-NAF metabolism, and CYP2C8, CYP2C19 and CYP3A4/5 inhibitors moderately inhibited S(−)-NAF metabolism. Consistent with the results of chemical inhibitors experiments, recombinant human CYP2C9 and CYP2C19 contributed greatly to R(+)-NAF metabolism, and CYP2C9 contributed greatly to S(−)-NAF metabolism.

Conclusion

Both R(+)-NAF and S(−)-NAF are metabolized to three metabolites in HLMs. CYP2C9 plays the most important role in the demethylation and hydroxylation of both NAF enantiomers, CYP2C19 is another major CYP isoform that is involved in R(+)-NAF metabolism.
Curcumin affects β-catenin pathway in hepatic stellate cell in vitro and in vivo
Authors: Cui Lei , Jia Xin , Zhou Qian , Zhai Xuguang , Zhou Yajun , Zhu Huixia
Published: June 2014

Objectives

Emerging evidence indicates that Wnt/β-catenin pathway is linked to the fibrosis of different organs including liver fibrosis. β-Catenin promotes hepatic stellate cells (HSCs) activation, a key event in the development of liver fibrosis, and has emerged as a novel mediator of fibrosis. Curcumin, a natural active ingredient derived from turmeric, possesses an inhibitory effect on liver fibrosis. This study is aimed to examine whether curcumin affects β-catenin expression/activity in HSCs and explores the underlying mechanisms.

Methods

The researchers used Western blot, real-time PCR, transfection assay and electrophoretic mobility shift assay and employed cultured HSCs and rat model of liver injury.

Key findings

Results showed that curcumin could reduce β-catenin protein level in HSCs in vitro and in vivo. Both β-catenin transactivation activity and DNA-binding activity were suppressed by curcumin. Moreover, nuclear β-catenin protein level was decreased by curcumin treatment. Further experiments suggested that delta-like homologue 1 contributed to curcumin inhibition of β-catenin transactivation activity in cultured HSCs.

Conclusions

Curcumin affects β-catenin pathway in HSCs and might suggest a possible new explanation for the effects of curcumin on HSC activation and liver fibrosis.
A randomized, controlled, clinical pilot study assessing the analgesic effect of morphine applied topically onto split-thickness skin wounds
Authors: Zaslansky Ruth , Ben-Nun Ohad , Ben-Shitrit Sima , Ullmann Yehuda , Kopf Andreas , Stein Christoph
Published: June 2014

Objectives

To assess the effect of an opioid administered topically onto a standardized skin wound in patients without significant comorbidity. Findings to date are contradictory, often obtained from multimorbid patients with wounds lacking uniformity.

Methods

Forty-four patients undergoing surgery for skin grafting were randomly assigned to receive morphine (0.25, 0.75 or 1.25 mg/100 cm2 wound size) in hydroxyethylcellulose gel or placebo applied onto the excised split-thickness donor wound at the end of surgery. Pain, supplementary systemic opioids and adverse effects were assessed during the first 24 h after application. Healing was examined when the dressings were removed.

Key findings

Morphine doses ranged from 0.25 to 5.4 mg (mean 1.93 ± standard deviation 1.34 mg). No differences in pain scores or use of supplementary analgesics were found between the groups. Serious adverse effects did not occur; healing was not impaired. Large intragroup variability was observed for pain scores, wound sizes and supplementary analgesia.

Conclusions

Patients treated with topically applied morphine gel onto standardized skin wounds did not report lower pain scores compared with placebo-treated patients. Larger groups would be required to arrive at definitive conclusions. The split-thickness skin graft model can be used for future research.
A comparative study on phenolic components and biological activity of some Senecio species in Turkey
Authors: Albayrak Sevil , Aksoy Ahmet , Yurtseven Lutfiye , Yaşar Abit
Published: June 2014

Objective

The phenolic components and biological activity of nine Senecio species growing in Turkey were investigated.

Methods

Senecio species were extracted with methanol. The content of total phenols was determined using Folin–Ciocalteu method, while individual phenolic acids and flavonoids were detected using HPLC analysis. Also, to determine the antioxidant capacity, phosphomolybdenum assay and 1,1-diphenyl picrylhydrazyl (DPPH) radical-scavenging activity assay were used. Antimicrobial activity of extract was determined using agar diffusion and broth microdilution method.

Key findings

The total phenolic contents of the extracts were found to be highest in Senecio cilicius and Senecio mollis extracts (117.45 and 113.40 mg equivalent to gallic acid/g, respectively). S. salsuginea showed the strongest free radical-scavenging activity with IC50 (the concentration providing 50% inhibition) = 26.23 μg/ml and S. mollis showed the highest antioxidant capacity in the phosphomolybdenum method (434.48 mg equivalent to ascorbic acid/g). The extracts exerted promising antibacterial activity against most of the test bacteria (minimal inhibitory concentration = 6.25–12.5 mg/ml), but no activity was observed against Candida albicans.

Conclusion

The results demonstrated that nine Senecio species possess high antioxidant and antimicrobial activity in accordance with the high amount of phenolic contents in the extracts that might be natural agencies used in many areas such as food, pharmacy and alternative medicine.
Comparative rangewide phylogeography of four endemic Taiwanese bat species
Authors: Kuo Hao‐Chih , Chen Shiang‐Fan , Fang Yin‐Ping , Flanders Jon , Rossiter Stephen J.
Published: June 2014

Phylogeographic reconstructions of codistributed taxa can help reveal the interplay between abiotic factors, such as altitude and climate, and species‐specific attributes, in shaping patterns of population genetic structure. Recent studies also demonstrate the value of both rangewide sampling and species distribution modelling (SDM) in comparative phylogeography. Here, we combine these approaches to study the population histories of four phylogenetically related forest‐dependent bat species. All are endemic to the mountainous island of Taiwan but show differences in their tolerance to altitude, with Murina gracilis considered to be a high‐altitude specialist, M. recondita and Kerivoula sp. low‐altitude specialists, and M. puta an altitudinal generalist. We tested the prediction that contrasting habitat preferences would impact on patterns of past and contemporary gene flow and found broad concordance between the results of population genetic analyses and species distribution models based on the Model for Interdisciplinary Research on Climate. Both lowland species showed evidence of genetic divergence between the east and west of the island, consistent with SDMs that indicated the Central Mountain Range (CMR) has presented a long‐term and continuous barrier to gene flow since before the Last Glacial Maximum. In contrast, Murina gracilis and M. puta showed lower degrees of historical isolation and genetic differentiation associated with the CMR, reflecting greater gene flow, possibly coupled with past population growth in M. puta. Together our results highlight the usefulness of combining distribution models with phylogeographic analyses to understand the drivers of genetic structure.
Co‐ordinated regulation of the extracytoplasmic stress factor, sigmaE, with other Escherichia coli sigma factors by (p)ppGpp and DksA may be achieved by specific regulation of individual holoenzymes
Authors: Gopalkrishnan Saumya , Nicoloff Herve , Ades Sarah E.
Published: June 2014

The E. coli alternative sigma factor, σE, transcribes genes required to maintain the cell envelope and is activated by conditions that destabilize the envelope. σE is also activated during entry into stationary phase in the absence of envelope stress by the alarmone (p)ppGpp. (p)ppGpp controls a large regulatory network, reducing expression of σ70‐dependent genes required for rapid growth and activating σ70‐dependent and alternative sigma factor‐dependent genes required for stress survival. The DksA protein often potentiates the effects of (p)ppGpp. Here we examine regulation of σE by (p)ppGpp and DksA following starvation for nutrients. We find that (p)ppGpp is required for increased σE activity under all conditions tested, but the requirement for DksA varies. DksA is required during amino acid starvation, but is dispensable during phosphate starvation. In contrast, regulation of σS is (p)ppGpp‐ and DksA‐dependent under all conditions tested, while negative regulation of σ70 is DksA‐ but not (p)ppGpp‐dependent during phosphate starvation, yet requires both factors during amino acid starvation. These findings suggest that the mechanism of transcriptional regulation by (p)ppGpp and/or DksA cannot yet be explained by a unifying model and is specific to individual promoters, individual holoenzymes, and specific starvation conditions.
Comparative analysis of the secretion capability of early and late flagellar type III secretion substrates
Authors: Singer Hanna M. , Erhardt Marc , Hughes Kelly T.
Published: June 2014

A remarkable feature of the flagellar‐specific type III secretion system (T3SS) is the selective recognition of a few substrate proteins among the many thousand cytoplasmic proteins. Secretion substrates are divided into two specificity classes: early substrates secreted for hook‐basal body (HBB) construction and late substrates secreted after HBB completion. Secretion was reported to require a disordered N‐terminal secretion signal, mRNA secretion signals within the 5′‐untranslated region (5′‐UTR) and for late substrates, piloting proteins known as the T3S chaperones. Here, we utilized translational β‐lactamase fusions to probe the secretion efficacy of the N‐terminal secretion signal of fourteen secreted flagellar substrates in Salmonella enterica. We observed a surprising variety in secretion capability between flagellar proteins of the same secretory class. The peptide secretion signals of the early‐type substrates FlgD, FlgF, FlgE and the late‐type substrate FlgL were analysed in detail. Analysing the role of the 5′‐UTR in secretion of flgB and flgE revealed that the native 5′‐UTR substantially enhanced protein translation and secretion. Based on our data, we propose a multicomponent signal that drives secretion via the flagellar T3SS. Both mRNA and peptide signals are recognized by the export apparatus and together with substrate‐specific chaperones allowing for targeted secretion of flagellar substrates.
Copper binding in IscA inhibits iron‐sulphur cluster assembly in Escherichia coli
Authors: Tan Guoqiang , Cheng Zishuo , Pang Yilin , Landry Aaron P. , Li Jianghui , Lu Jianxin , Ding Huangen
Published: June 2014

Among the iron‐sulphur cluster assembly proteins encoded by gene cluster iscSUA‐hscBA‐fdx in Escherichia coli, IscA has a unique and strong iron binding activity and can provide iron for iron‐sulphur cluster assembly in proteins in vitro. Deletion of IscA and its paralogue SufA results in an E. coli mutant that fails to assemble [4Fe‐4S] clusters in proteins under aerobic conditions, suggesting that IscA has a crucial role for iron‐sulphur cluster biogenesis. Here we report that among the iron‐sulphur cluster assembly proteins, IscA also has a strong and specific binding activity for Cu(I) in vivo and in vitro. The Cu(I) centre in IscA is stable and resistant to oxidation under aerobic conditions. Mutation of the conserved cysteine residues that are essential for the iron binding in IscA abolishes the copper binding activity, indicating that copper and iron may share the same binding site in the protein. Additional studies reveal that copper can compete with iron for the metal binding site in IscA and effectively inhibits the IscA‐mediated [4Fe‐4S] cluster assembly in E. coli cells. The results suggest that copper may not only attack the [4Fe‐4S] clusters in dehydratases, but also block the [4Fe‐4S] cluster assembly in proteins by targeting IscA in cells.
Prompting professional prerogatives: New insights to reopen an old debate about nursing
Authors: Ayala Ricardo A. , Vanderstraeten Raf , Bracke Piet
Published: June 2014

A profession is defined by neither a set of structural qualities nor a description idiosyncratic to a single culture. Rather, a profession detects problems in an area of work, intellectualizes that work, and offers solutions, developing a logic of competition with coexisting occupations. The best that structural explanations can offer to nursing is rigid, unmovable definitions such as “a semi‐profession,” whereas the ecological theory of the professions regards the continuous interplay among occupations cohabiting in an interacting system as the fundamental process of gaining or losing professional status. In this theoretically driven article we draw upon the notion of “social ecology of nursing” as a vector of development, arguing that nursing's professional status lies in its ability to adapt to “landscape” transformations and to protect its jurisdiction from competitors, equating fully established professions. In discussing the application of this theory, we invite readers to reopen a debate about the professional nature of nursing, considering cross‐national versions of nursing for more comprehensive definitions of the profession.