bluuebunny/crossref_metadata_2025 huggingface dataset:
Acupuncture for low back pain: ritual healing or medicine?
Authors: Kavoussi Ben
Published: January 2015

Background

Low back pain (LBP) is a prevalent and costly condition that is poorly amenable to medical care. Both patients and clinicians occasionally resort to non‐medical healing such as acupuncture.

Objectives

The aim of this narrative review is to evaluate acupuncture's claim of efficacy as an adjunct or alternative therapy for the treatment of non‐specific, non‐inflammatory LBP with no neurological symptoms.

Methods

Evidence was collected from clinical trials, meta‐analyses and systematic reviews conducted in the USA or in Europe. Studies were all published in English, conducted within the last 10 years, and identified exclusively from PubMed, CINAHL and the Cochrane Collaboration.

Results

Collectively, recent RCTs and systematic reviews provide consistent evidence that acupuncture according to its traditional theories is no more effective for LBP than various forms of non‐invasive controls, including pricking the skin with a toothpick at non‐acupuncture points. This finding not only undermines the traditional tenets of acupuncture, but also discredits its claim of specific effects for LBP.

Conclusions

If the effects of acupuncture on LBP are mainly due to the treatment ritual or to other psychological factors, then the placebo nature of the treatment must be fully disclosed; otherwise, patients will not be making an informed medical decision. Moreover, the use of acupuncture for LBP might directly conflict with the current positions of the American Medical Association, the American Osteopathic Association, the American Pain Society and the American Society for Pain Management Nursing on the use of placebo for the treatment of pain.
Complete catalytic cycle of cofactor‐independent phosphoglycerate mutase involves a spring‐loaded mechanism
Authors: Roychowdhury Amlan , Kundu Anirban , Bose Madhuparna , Gujar Akanksha , Mukherjee Somnath , Das Amit Kumar
Published: January 2015

Cofactor‐independent phosphoglycerate mutase (iPGM), an important enzyme in glycolysis and gluconeogenesis, catalyses the isomerization of 2‐ and 3‐phosphoglycerates by an Mn2+‐dependent phospho‐transfer mechanism via a phospho‐enzyme intermediate. Crystal structures of bi‐domain iPGM from Staphylococcus aureus, together with substrate‐bound forms, have revealed a new conformation of the enzyme, representing an intermediate state of domain movement. The substrate‐binding site and the catalytic site are present in two distinct domains in the intermediate form. X–ray crystallography complemented by simulated dynamics has enabled delineation of the complete catalytic cycle, which includes binding of the substrate, followed by its positioning into the catalytic site, phospho‐transfer and finally product release. The present work describes a novel mechanism of domain movement controlled by a hydrophobic patch that is exposed on domain closure and acts like a spring to keep the protein in open conformation. Domain closing occurs after substrate binding, and is essential for phospho‐transfer, whereas the open conformation is a prerequisite for efficient substrate binding and product dissociation. A new model of catalysis has been proposed by correlating the hinge‐bending motion with the phospho‐transfer mechanism.
Estrogen receptors α and β have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons
Authors: Sá Susana I. , Fonseca Bruno M. , Teixeira Natércia , Madeira M. Dulce
Published: January 2015

Progesterone receptor (PR) activation in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is essential for promoting female sexual behavior. Estrogen receptor (ER) α, in contrast to ERβ, has been implicated in the induction of PRs. The simultaneous activation of ERα and ERβ, although not increasing the number of PR‐immunoreactive neurons in the VMNvl, facilitates lordosis, which suggests that ERβ and/or the ERα–ERβ interaction might play a role in PR dynamics and/or PR expression by individual neurons. To address this question, we used western blot and immunohistochemical studies to determine the amounts and subcellular distributions of both PR isoforms in VMNvl neurons of ovariectomized rats injected with estradiol benzoate or with specific agonists of ERα and ERβ, alone or in association. The present data show that ERα activation does not change PR expression in individual neurons, but increases the number of PRs in the VMNvl, because it increases the number of neurons expressing PRs. Conversely, ERβ activation does not change the total number of PRs in the VMNvl, but increases the labeling intensity of the perikaryal cytoplasm, which suggests that it promotes the transport of PRs from neurites into cell bodies. In addition, the simultaneous activation of ERα and ERβ increases the expression of PRs by individual neurons and, consequently, increases the total number of PRs in the VMNvl. Our findings reveal that individual and simultaneous activation of ERα and ERβ have different effects on the levels and subcellular location of PRs in VMNvl neurons.
Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric disorders
Authors: Freudenberg F. , Alttoa A. , Reif A.
Published: January 2015

Nitric oxide (NO) is a gaseous transmitter produced by nitric oxide synthases (NOSs). The neuronal isoform (NOS‐I, encoded by NOS1) is the main source of NO in the central nervous system (CNS). Animal studies suggest that nitrinergic dysregulation may lead to behavioral abnormalities. Unfortunately, the large number of animal studies is not adequately reflected by publications concerning humans. These include post‐mortem studies, determination of biomarkers, and genetic association studies. Here, we review the evidence for the role of NO in psychiatric disorders by focusing on the human NOS1 gene as well as biomarker studies. Owing to the complex regulation of NOS1 and the varying function of NOS‐I in different brain regions, no simple, unidirectional association is expected. Rather, the ‘where, when and how much’ of NO formation is decisive. Present data, although still preliminary and partially conflicting, suggest that genetically driven reduced NO signaling in the prefrontal cortex is associated with schizophrenia and cognition. Both NOS1 and its interaction partner NOS1AP have a role therein. Also, reduced NOS1 expression in the striatum determined by a length polymorphism in a NOS1 promoter (NOS1 ex1f‐VNTR) goes along with a variety of impulsive behaviors. An association of NOS1 with mood disorders, suggested by animal models, is less clear on the genetic level; however, NO metabolites in blood may serve as biomarkers for major depression and bipolar disorder. As the nitrinergic system comprises a relevant target for pharmacological interventions, further studies are warranted not only to elucidate the pathophysiology of mental disorders, but also to evaluate NO function as a biomarker.
Forecasted coral reef decline in marine biodiversity hotspots under climate change
Authors: Descombes Patrice , Wisz Mary S. , Leprieur Fabien , Parravicini Valerianio , Heine Christian , Olsen Steffen M. , Swingedouw Didier , Kulbicki Michel , Mouillot David , Pellissier Loïc
Published: January 2015

Coral bleaching events threaten coral reef habitats globally and cause severe declines of local biodiversity and productivity. Related to high sea surface temperatures (SST), bleaching events are expected to increase as a consequence of future global warming. However, response to climate change is still uncertain as future low‐latitude climatic conditions have no present‐day analogue. Sea surface temperatures during the Eocene epoch were warmer than forecasted changes for the coming century, and distributions of corals during the Eocene may help to inform models forecasting the future of coral reefs. We coupled contemporary and Eocene coral occurrences with information on their respective climatic conditions to model the thermal niche of coral reefs and its potential response to projected climate change. We found that under the RCP8.5 climate change scenario, the global suitability for coral reefs may increase up to 16% by 2100, mostly due to improved suitability of higher latitudes. In contrast, in its current range, coral reef suitability may decrease up to 46% by 2100. Reduction in thermal suitability will be most severe in biodiversity hotspots, especially in the Indo‐Australian Archipelago. Our results suggest that many contemporary hotspots for coral reefs, including those that have been refugia in the past, spatially mismatch with future suitable areas for coral reefs posing challenges to conservation actions under climate change.
Leaf and stem economics spectra drive diversity of functional plant traits in a dynamic global vegetation model
Authors: Sakschewski Boris , von Bloh Werner , Boit Alice , Rammig Anja , Kattge Jens , Poorter Lourens , Peñuelas Josep , Thonicke Kirsten
Published: January 2015

Functional diversity is critical for ecosystem dynamics, stability and productivity. However, dynamic global vegetation models (DGVMs) which are increasingly used to simulate ecosystem functions under global change, condense functional diversity to plant functional types (PFTs) with constant parameters. Here, we develop an individual‐ and trait‐based version of theDGVM LPJmL (Lund‐Potsdam‐Jena managed Land) calledLPJmL‐ flexible individual traits (LPJmL‐FIT) with flexible individual traits) which we apply to generate plant trait maps for the Amazon basin.LPJmL‐FITincorporates empirical ranges of five traits of tropical trees extracted from theTRYglobal plant trait database, namely specific leaf area (SLA), leaf longevity (LL), leaf nitrogen content (Narea), the maximum carboxylation rate of Rubisco per leaf area (), and wood density (WD). To scale the individual growth performance of trees, the leaf traits are linked by trade‐offs based on the leaf economics spectrum, whereas wood density is linked to tree mortality. No preselection of growth strategies is taking place, because individuals with unique trait combinations are uniformly distributed at tree establishment. We validate the modeled trait distributions by empirical trait data and the modeled biomass by a remote sensing product along a climatic gradient. Including trait variability and trade‐offs successfully predicts natural trait distributions and achieves a more realistic representation of functional diversity at the local to regional scale. As sites of high climatic variability, the fringes of the Amazon promote trait divergence and the coexistence of multiple tree growth strategies, while lower plant trait diversity is found in the species‐rich center of the region with relatively low climatic variability.LPJmL‐FITenables to test hypotheses on the effects of functional biodiversity on ecosystem functioning and to apply theDGVMto current challenges in ecosystem management from local to global scales, that is, deforestation and climate change effects.
Inclusion of ecologically based trait variation in plant functional types reduces the projected land carbon sink in an earth system model
Authors: Verheijen Lieneke M. , Aerts Rien , Brovkin Victor , Cavender‐Bares Jeannine , Cornelissen Johannes H. C. , Kattge Jens , van Bodegom Peter M.
Published: January 2015

Earth system models demonstrate large uncertainty in projected changes in terrestrial carbon budgets. The lack of inclusion of adaptive responses of vegetation communities to the environment has been suggested to hamper the ability of modeled vegetation to adequately respond to environmental change. In this study, variation in functional responses of vegetation has been added to an earth system model (ESM) based on ecological principles. The restriction of viable mean trait values of vegetation communities by the environment, called ‘habitat filtering’, is an important ecological assembly rule and allows for determination of global scale trait–environment relationships. These relationships were applied to model trait variation for different plant functional types (PFTs). For three leaf traits (specific leaf area, maximum carboxylation rate at 25 °C, and maximum electron transport rate at 25 °C), relationships with multiple environmental drivers, such as precipitation, temperature, radiation, and CO2, were determined for the PFTs within the Max Planck Institute ESM. With these relationships, spatiotemporal variation in these formerly fixed traits in PFTs was modeled in global change projections (IPCC RCP8.5 scenario). Inclusion of this environment‐driven trait variation resulted in a strong reduction of the global carbon sink by at least 33% (2.1 Pg C yr−1) from the 2nd quarter of the 21st century onward compared to the default model with fixed traits. In addition, the mid‐ and high latitudes became a stronger carbon sink and the tropics a stronger carbon source, caused by trait‐induced differences in productivity and relative respirational costs. These results point toward a reduction of the global carbon sink when including a more realistic representation of functional vegetation responses, implying more carbon will stay airborne, which could fuel further climate change.
Self‐Activated Vanadate Compounds Toward Realization of Rare‐Earth‐Free Full‐Color Phosphors
Authors: Matsushima Yuta , Koide Takuhiro , Hiro‐Oka Masahiro , Shida Minori , Sato Akane , Sugiyama Sho , Ito Michimasa
Published: January 2015

Rare‐earth‐free phosphors based on vanadate compounds were investigated, where the vanadates included chloride vanadates (MII2VO4Cl), pyrovanadates (MII2V2O7), orthovanadates (MII3(VO4)2) with divalent cations MII of Mg, Sr, Ba, and Zn, and oxofluorovanadates (AIVOF4) with an alkali metal AI. A chloride pyrolysis method and a liquid phase precipitation method were proposed for preparing the chloride vanadates and pyro‐ and orthovanadates, respectively. These vanadate compounds showed self‐activated photoluminescence (PL) based on the VO4 clusters against the ultraviolet (UV) light irradiation. The colors of PL covered almost the whole visible‐light region from blue to yellow as Sr2VO4Cl (deep blue), Ca2VO4Cl (sky blue), Ba2V2O7 (green), Sr2V2O7 (yellowish green), Zn3(VO4)2 (yellow), and Mg3(VO4)2 (yellow). A correlation was suggested from these compounds between the luminescent colors and the structural feature as the longer V–O distances in the VO4 tetrahedra in the crystal structures led to the longer wavelength in PL. This seemed to be also applicable for the oxofluorovanadates AIVOF4 (AI = K and Cs) which contain the VOF4 polyhedra with one O2− ion and four F‐ ions as the ligands, as they exhibited the reddish PL.
Improvements and Modifications to Room‐Temperature Fabrication Method for Dielectric Li2MoO4 Ceramics
Authors: Kähäri Hanna , Teirikangas Merja , Juuti Jari , Jantunen Heli
Published: January 2015

Dielectric properties of lithium molybdate disks fabricated by moistening water‐soluble Li2MoO4 powder, compressing it, and postprocessing the samples at 120°C, were improved by the optimization of powder particle size, sample pressing pressure, and postprocessing time. It appeared that the postprocessing temperature of the Li2MoO4 ceramics could be chosen so as to be applicable to the associated integrated materials as long as the postprocessing time was adequately adjusted to ensure the removal of the residual water. In addition, the dielectric properties of Li2MoO4 ceramic were modified with an inclusion of suitable additives. For example, at 1 GHz the relative permittivity of Li2MoO4 disks fabricated at room temperature and postprocessed at 120°C was increased from 6.4 to 8.8 with an addition of 10 vol% of rutile TiO2 and to 9.7 with an addition of 10 vol% of BaTiO3. At the same time the loss tangent value increased from 0.0006 to 0.0014 and to 0.011, respectively.
Micro‐reactors to Study Alite Hydration
Authors: Suraneni Prannoy , Flatt Robert J.
Published: January 2015

A new approach to study the early hydration reaction of alite is presented. It relies on milling micron‐sized gaps into alite grains using a Focused Ion Beam. This provides for a “micro‐reactor” in which hydration in confined conditions can be followed after introducing aqueous solutions of any desired composition. Hydration is followed by stopping the reaction at desired ages using solvent exchange and imaging the gaps using a Scanning Electron Microscope. These micro‐reactors offer several advantages over conventional methods to monitor alite hydration. In particular, we can study the time evolution of dissolution in a reproducible manner using a setup that mimics particles in close contact. This paper presents this new methodology and applies it to studying the effects of solution composition and selected chemical admixtures on the dissolution of alite. New insights into the role of these factors are obtained and discussed.
X9R BaTiO3‐Based Dielectric Ceramics with Multilayer Core–Shell Structure Produced by Polymer‐Network Gel Coating Method
Authors: Wang Ting , Hao Hua , Liu Mengying , Zhou Dongdong , Yao Zhonghua , Cao Minghe , Liu Hanxing
Published: January 2015

The modified polymer‐network gel route has been developed to prepare a multilayer core–shell structure of BaTiO3‐based dielectric ceramics. The core of particle was BaTiO3, whereas 0.7BaTiO3–0.3Bi(Zn1/2Ti1/2)O3 (0.7BT–0.3BZT) and Nb oxides were coated as the multilayer shell compositions, which were confirmed by energy dispersive spectroscopy testing. The dielectric properties of BaTiO3‐based samples with multilayer core–shell structure were found to meet the X9R specification. The dielectric constant was 1190 and the dielectric loss was 1.3% at room temperature.
Transcontinental migratory connectivity predicts parasite prevalence in breeding populations of the European barn swallow
Authors: von Rönn J. A. C. , Harrod C. , Bensch S. , Wolf J. B. W.
Published: January 2015

Parasites exert a major impact on the eco‐evolutionary dynamics of their hosts and the associated biotic environment. Migration constitutes an effective means for long‐distance invasions of vector‐borne parasites and promotes their rapid spread. Yet, ecological and spatial information on population‐specific host–parasite connectivity is essentially lacking. Here, we address this question in a system consisting of a transcontinental migrant species, the European barn swallow (Hirundo rustica) which serves as a vector for avian endoparasites in the genera Plasmodium, Haemoproteus and Leucocytozoon. Using feather stable isotope ratios as geographically informative markers, we first assessed migratory connectivity in the host: Northern European breeding populations predominantly overwintered in dry, savannah‐like habitats in Southern Africa, whereas Southern European populations were associated with wetland habitats in Western Central Africa. Wintering areas of swallows breeding in Central Europe indicated a migratory divide with both migratory programmes occurring within the same breeding population. Subsequent genetic screens of parasites in the breeding populations revealed a link between the host's migratory programme and its parasitic repertoire: controlling for effects of local breeding location, prevalence of Africa‐transmitted Plasmodium lineages was significantly higher in individuals overwintering in the moist habitats of Western Central Africa, even among sympatrically breeding individuals with different overwintering locations. For the rarer Haemoproteus parasites, prevalence was best explained by breeding location alone, whereas no clear pattern emerged for the least abundant parasite Leucocytozoon. These results have implications for our understanding of spatio‐temporal host–parasite dynamics in migratory species and the spread of avian borne diseases.
An emergency response‐type rainfall‐runoff‐inundation simulation for 2011 Thailand floods
Authors: Sayama T. , Tatebe Y. , Tanaka S.
Published: January 2015

A devastating flood disaster occurred in Thailand in 2011. In case of such large‐scale flooding, it is important to predict the dynamics of inundation on a near real‐time basis for safe evacuation. To predict widespread inundation, where both rainfall‐runoff from surrounding mountains and rainfall on floodplains contribute to the event, this paper applied a rainfall‐runoff‐inundation (RRI) model to the entire Chao Phraya River basin (160 000 km2). Near real‐time simulation was conducted for emergency responses with globally available dataset including satellite‐based topography (HydroSHEDS derived from SRTM) and rainfall (TRMM 3B42RT) during the disaster. Post‐flood simulation was also carried out with more local information. The RRI model was found capable of representing the peak inundation extent with an acceptable accuracy and correctly predicting a 1‐month lasting inundation in the lower part of the basin. On the other hand, the prediction overestimated the river discharge by 40% and the inundation water level by 2 m mainly due to the neglect of the evapotranspiration effect. The post‐flood simulation improved its accuracy by up to 10% for river discharges and 1 m for peak inundation water levels, but it did not lead to better agreement of flood extents with those based on the remote sensing. Further study is recommended to improve accuracy for modelling of spatial extent of flooding. Furthermore, sensitivity analysis with different input suggested what information should be prioritised for emergency response‐type flood simulations.
Prevalence of gastroesophageal reflux disease in children, adults, and elderly in the same community
Authors: Okimoto Eiko , Ishimura Norihisa , Morito Yoshiya , Mikami Hironobu , Shimura Shino , Uno Goichi , Tamagawa Yuji , Aimi Masahito , Oshima Naoki , Kawashima Kousaku , Kazumori Hideaki , Sato Shuichi , Ishihara Shunji , Kinoshita Yoshikazu
Published: January 2015

Background and Aim

The prevalence of gastroesophageal reflux disease (GERD) in adults is increasing in Japan as well as worldwide likely due to increasing obesity and the decreasing rate of Helicobacter pylori infection. However, data regarding the prevalence of GERD in children and adolescents in Japan are lacking. We investigated the prevalence of GERD in children, adults, and elderly living in the same community.

Methods

We surveyed employees of Shimane University Hospital and a related facility and their families using the Gastroesophageal Reflux Disease Questionnaire (GerdQ) and Izumo Scale instruments with demographic information (age, sex, body height, and body weight) and information regarding concurrent medication being taken for GERD. The presence of GERD was defined as a GerdQ score of ≥ 8.

Results

A total of 1859 subjects (771 males, 1088 females; 6–96 years old) were eligible for assessment. The prevalence of GERD in those under 20 years old was 4.4%, which was approximately one third of the rate in adults (11.6%). GERD prevalence was closely associated with obesity in adults, but not in subjects under 20 years old. GERD and other gastrointestinal symptoms frequently overlapped in both adults and younger subjects.

Conclusion

We found that the prevalence of GERD in subjects under 20 years of age was lower than that in adults and not associated with obesity. Nevertheless, it is important to be aware of symptoms such as heartburn and/or regurgitation when children and adolescents seek routine clinical care.
Interleukin‐8: A critical chemokine in biliary atresia
Authors: Dong Rui , Zheng Shan
Published: January 2015

Biliary atresia (BA) is characterized by periductular inflammation and fibrosis and is associated with the progressive obliteration of the bile ducts. The induction and maintenance of systemic and local inflammatory responses plays a pivotal role in this process. Interleukin‐8 (IL‐8) is an important mediator of inflammation and the immune response in human disease. IL‐8 is overexpressed in BA, and its expression positively correlates with inflammation and liver fibrosis. In this review, we focus on the available evidence, recent insights, and future clinical and preclinical possibilities regarding the role of IL‐8 in BA.
Ideal colonoscopic surveillance intervals to reduce incidence of advanced adenoma and colorectal cancer
Authors: Good Norm M , Macrae Finlay A , Young Graeme P , O'Dywer John , Slattery Masha , Venables William , Lockett Trevor J , O'Dwyer Marilla
Published: January 2015

Background and Aims

There is limited information about the interplay between multiple risk factors contributing to the risk of advanced neoplasia. We determined the actual risk for advanced neoplasia in relation to lapsed time between colonoscopies in people enrolled in a structured surveillance program. This risk information can be used to guide the selection of optimal surveillance intervals.

Methods

Patients were recruited into programs at two major tertiary hospitals, with a personal or family history of advanced neoplasia. Five thousand one hundred forty‐one patients had an index and one or more surveillance colonoscopies. Fifty‐one percent had a family history of colorectal neoplasia while the remainder had a personal history.

Results

Patients with an immediately prior colonoscopy result (prior result) of advanced adenoma had a risk for advanced neoplasia 7.1 times greater than those with a normal prior result. Cancer as a prior result did not confer a greater risk than either a hyperplastic polyp or a nonadvanced adenoma. Being female reduced risk, age increased risk. Only a family history of a first‐degree relative diagnosed under 55, or definite or suspected hereditary nonpolyposis colorectal cancer (HNPCC) conferred an increased risk over a personal history of advanced neoplasia.

Conclusions

Most family history categories did not confer excess risk above personal history of advanced neoplasia. A prior cancer poses less of a risk than a prior advanced adenoma. Based on our models, a person with an advanced adenoma should be scheduled for colonoscopy at 3 years, corresponding to a 15% risk of advanced neoplasia for a male aged under 56. Guidelines should be updated that uses a 15% risk as a benchmark for calculating surveillance intervals.
The biosynthesis and wall‐binding of hemicelluloses in cellulose‐deficient maize cells: An example of metabolic plasticity
Authors: de Castro María , Miller Janice G. , Acebes José Luis , Encina Antonio , García‐Angulo Penélope , Fry Stephen C.
Published: January 2015

Cell‐suspension cultures (Zea mays L., Black Mexican sweet corn) habituated to 2,6‐dichlorobenzonitrile (DCB) survive with reduced cellulose owing to hemicellulose network modification. We aimed to define the hemicellulose metabolism modifications in DCB‐habituated maize cells showing a mild reduction in cellulose at different stages in the culture cycle. Using pulse‐chase radiolabeling, we fed habituated and non‐habituated cultures with [3H]arabinose, and traced the distribution of 3H‐pentose residues between xylans, xyloglucans and other polymers in several cellular compartments for 5 h. Habituated cells were slower taking up exogenous [3H]arabinose. Tritium was incorporated into polysaccharide‐bound arabinose and xylose residues, but habituated cells diverted a higher proportion of their new [3H]xylose residues into (hetero) xylans at the expense of xyloglucan synthesis. During logarithmic growth, habituated cells showed slower vesicular trafficking of polymers, especially xylans. Moreover, habituated cells showed a decrease in the strong wall‐binding of all pentose‐containing polysaccharides studied; correspondingly, especially in log‐phase cultures, habituation increased the proportion of 3H‐hemicelluloses ([3H]xylans and [3H]xyloglucan) sloughed into the medium. These findings could be related to the cell walls' cellulose‐deficiency, and consequent reduction in binding sites for hemicelluloses; the data could also reflect the habituated cells' reduced capacity to integrate arabinoxylans by extra‐protoplasmic phenolic cross‐linking, as well as xyloglucans, during wall assembly.
Evaluation of the immunomodulatory effect of melatonin on the T‐cell response in peripheral blood from systemic lupus erythematosus patients
Authors: Medrano‐Campillo Pablo , Sarmiento‐Soto Helia , Álvarez‐Sánchez Nuria , Álvarez‐Ríos Ana I. , Guerrero Juan M. , Rodríguez‐Prieto Ismael , Castillo‐Palma María Jesús , Lardone Patricia J. , Carrillo‐Vico Antonio
Published: January 2015

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of antinuclear autoantibodies. In addition, the involvement of CD4+ T‐helper (Th) cells in SLE has become increasingly evident. Although the role of melatonin has been tested in some experimental models of lupus with inconclusive results, there are no studies evaluating the melatonin effect on cells from patients with SLE. Therefore, the aim of this study was to analyse the role of in vitro administered melatonin in the immune response of peripheral leukocytes from treated patients with SLE (n = 20) and age‐ and sex‐matched healthy controls. Melatonin was tested for its effect on the production of key Th1, Th2, Th9, Th17 and innate cytokines. The frequency of T regulatory (Treg) cells and the expression of FOXP3 and BAFF were also explored. Our results are the first to show that melatonin decreased the production of IL‐5 and to describe the novel role of melatonin in IL‐9 production by human circulating cells. Additionally, we highlighted a two‐faceted melatonin effect. Although it acted as a prototypical anti‐inflammatory compound, reducing exacerbated Th1 and innate responses in PHA‐stimulated cells from healthy subjects, it caused the opposite actions in immune‐depressed cells from patients with SLE. Melatonin also increased the number of Treg cells expressing FOXP3 and offset BAFF overexpression in SLE patient cells. These findings open a new field of research in lupus that could lead to the use of melatonin as treatment or cotreatment for SLE.
Melatonin uptake through glucose transporters: a new target for melatonin inhibition of cancer
Authors: Hevia David , González‐Menéndez Pedro , Quiros‐González Isabel , Miar Ana , Rodríguez‐García Aida , Tan Dun‐Xian , Reiter Russel J. , Mayo Juan C. , Sainz Rosa M.
Published: January 2015

Melatonin is present in a multitude of taxa and it has a broad range of biological functions, from synchronizing circadian rhythms to detoxifying free radicals. Some functions of melatonin are mediated by its membrane receptors but others are receptor‐independent. For the latter, melatonin must enter into the cell. Melatonin is a derivative of the amino acid tryptophan and reportedly easily crosses biological membranes due to its amphipathic nature. However, the mechanism by which melatonin enters into cells remains unknown. Changes in redox state, endocytosis pathways, multidrug resistance, glycoproteins or a variety of strategies have no effect on melatonin uptake. Herein, it is demonstrated that members of the SLC2/GLUT family glucose transporters have a central role in melatonin uptake. When studied by docking simulation, it is found that melatonin interacts at the same location in GLUT1 where glucose does. Furthermore, glucose concentration and the presence of competitive ligands of GLUT1 affect the concentration of melatonin into cells. As a regulatory mechanism, melatonin reduces the uptake of glucose and modifies the expression of GLUT1 transporter in prostate cancer cells. More importantly, glucose supplementation promotes prostate cancer progression in TRAMP mice, while melatonin attenuated glucose‐induced tumor progression and prolonged the lifespan of tumor‐bearing mice. This is the first time that a facilitated transport of melatonin is suggested. In fact, the important role of glucose transporters and glucose metabolism in cell fate might explain some of the diverse functions described for melatonin.
From multifamily residences to studio apartments: shifts in burrow structures of European rabbits along a rural‐to‐urban gradient
Authors: Ziege M. , Brix M. , Schulze M. , Seidemann A. , Straskraba S. , Wenninger S. , Streit B. , Wronski T. , Plath M.
Published: January 2015

European rabbits (Oryctolagus cuniculus) are currently declining in most rural areas throughout central Europe, while city populations often reach high densities. We asked whether and how altered environmental conditions affect the social organization and burrow structures of European rabbit populations located at urban, suburban and rural sites in and around Frankfurt a.M. in Germany. Burrow densities (numbers per ha) increased along the rural‐to‐urban gradient, accompanied by a gradual shift from accumulated towards more evenly distributed burrows. Burrows became smaller and less complex with increasing degree of urbanity, and accordingly, also the number of rabbits inhabiting the same burrow decreased. It remains unclear whether urbanization first led to smaller rabbit group sizes and burrow structures then shifted as a consequence of this, or vice versa. Nevertheless, for both scenarios, we propose that increased structural heterogeneity of urban landscapes is the major factor behind the observed effects, as mosaic‐like habitat patches in cities provide high and steady resource availability compared with the agriculturally transformed, open landscapes characterizing most rural areas in central Europe.
The use of beta‐blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis
Authors: Sersté Thomas , Njimi Hassane , Degré Delphine , Deltenre Pierre , Schreiber Jonas , Lepida Antonia , Trépo Eric , Gustot Thierry , Moreno Christophe
Published: January 2015

Background & Aims

The beneficial effect of nonselective beta‐blockers (NSBB) has recently been questioned in patients with end‐stage cirrhosis. We analysed the impact of NSBB on outcomes in severe alcoholic hepatitis (AH).

Methods

This study was based on a prospective database of patients with severe, biopsy‐proven AH. Patients admitted from July, 2006 to July, 2014 were retrospectively studied. Patients were divided into two groups (with and without NSBB) and assessed for the occurrence of Acute Kidney Injury (AKI) and transplant‐free mortality during a 168‐day follow‐up period.

Results

One hundred thirty‐nine patients were included, the mean Maddrey score was 71 ± 34 and 86 patients (61.9%) developed AKI. Forty‐eight patients (34.5%) received NSBB. The overall 168‐day transplant‐free mortality was 50.5% (95%CI, 41.3–60.0%). The overall 168‐day cumulative incidence of AKI was 61.9% (95%CI, 53.2–69.4%). When compared, patients with NSBB had a lower heart rate (65 ± 13 vs 92 ± 12, P < 0.0001) and a lower mean arterial pressure (MAP, 78 ± 3 vs 87 ± 5, P < 0.0001). Patients with NSBB had comparable MELD scores, Maddrey scores, and medical histories. The 168‐day transplant‐free mortality was 56.8% (95%CI, 41.3–69.7%) in patients with NSBB and 46.7% (95%CI, 35.0–57.6%) without NSBB (P = 0.25). The 168‐day cumulative incidence of AKI was 89.6% (95%CI, 74.9–95.9%) with NSBB compared to 50.4% (95%CI: 39.0–60.7) for no NSBB (P = 0.0001). The independent factors predicting AKI were a higher MELD score and the presence of NSBB.

Conclusions

The use of NSBB in patients with severe AH is independently associated with a higher cumulative incidence of AKI.
Precore/Core promoter variants to predict significant fibrosis in both HBeAg positive and negative chronic hepatitis B
Authors: Lapalus Martine , Laouenan Cédric , Cardoso Ana‐Carolina , Estrabaud Emilie , Carvalho‐Filho Roberto J. , Zhang Qian , Lada Olivier , Appourchaux Kevin , Mouri Feryel , Boyer Nathalie , Bedossa Pierre , Asselah Tarik , Martinot‐Peignoux Michelle , Marcellin Patrick
Published: January 2015

Background & Aims

Assessing fibrosis is essential in patients with chronic hepatitis B (CHB). The objective was to investigate the relationship between fibrosis, host and viral factors to identify non‐invasive markers of significant fibrosis in a large cohort of unselected, well‐characterized, treatment‐naïve CHB patients.

Methods

Three hundred and seventy‐seven HBsAg‐positive patients (97 HBeAg‐positive and 280 HBeAg‐negative, genotypes A to E) who had liver biopsy were consecutively included. Host and viral factors (ALT, HBsAg and HBV‐DNA levels, HBV genotype and precore (PC)/basal core promoter (BCP) variants) were determined on the day of the biopsy. Fibrosis stage was assessed using METAVIR score.

Results

Thirty‐nine percent of the patients had significant fibrosis (METAVIR F ≥ 2). On univariate analysis, the stages of fibrosis F ≥ 2 were associated with older age (P < 0.0001), male gender (P = 0.01), higher ALT and HBV‐DNA levels (P < 0.0001 and P = 0.0003, respectively), the presence of BCP (P < 0.0001) and BCP/PC variants (P < 0.0001). On multivariate analysis, age (P < 0.0001), the presence of HBV variants (P < 0.0001), HBV‐DNA level (P = 0.0006) and ALT level (P = 0.02) were independently associated with significant fibrosis. The diagnostic accuracy of the combination (age, ALT, HBV‐DNA, HBV variants) in predicting fibrosis F ≥ 2 was evidenced by a c‐index of 0.76 (CI 95% 0.71–0.81).

Conclusions

We identified strong independent risk factors (age, ALT, HBV‐DNA, HBV variants) predicting significant fibrosis (F ≥ 2) independently of HBeAg status in patients with CHB. Patients with BCP variants have a higher risk of severe liver disease. The detection of these mutants may help to predict significant fibrosis (F ≥ 2).
Host association drives genetic divergence in the bed bug, Cimex lectularius
Authors: Booth Warren , Balvín Ondřej , Vargo Edward L. , Vilímová Jitka , Schal Coby
Published: January 2015

Genetic differentiation may exist among sympatric populations of a species due to long‐term associations with alternative hosts (i.e. host‐associated differentiation). While host‐associated differentiation has been documented in several phytophagus insects, there are far fewer cases known in animal parasites. The bed bug, Cimex lectularius, a wingless insect, represents a potential model organism for elucidating the processes involved in host‐associated differentiation in animal parasites with relatively limited mobility. In conjunction with the expansion of modern humans from Africa into Eurasia, it has been speculated that bed bugs extended their host range from bats to humans in their shared cave domiciles throughout Eurasia. C. lectularius that associate with humans have a cosmopolitan distribution, whereas those associated with bats occur across Europe, often in human‐built structures. We assessed genetic structure and gene flow within and among populations collected in association with each host using mtDNA, microsatellite loci and knock‐down resistance gene variants. Both nuclear and mitochondrial data support a lack of significant contemporary gene flow between host‐specific populations. Within locations human‐associated bed bug populations exhibit limited genetic diversity and elevated levels of inbreeding, likely due to human‐mediated movement, infrequent additional introduction events per infestation, and pest control. In contrast, populations within bat roosts exhibit higher genetic diversity and lower levels of relatedness, suggesting populations are stable with temporal fluctuations due to host dispersal and bug mortality. In concert with previously published evidence of morphological and behavioural differentiation, the genetic data presented here suggest C. lectularius is currently undergoing lineage divergence through host association.
Molecular and cellular pathogenesis of adamantinomatous craniopharyngioma
Authors: Martinez‐Barbera Juan Pedro
Published: January 2015

Adamantinomatous craniopharyngiomas (ACPs) are the most common pituitary tumours in children. Although histologically benign, these are clinically aggressive tumours, difficult to manage and associated with poor quality of life for the patients. Several human and mouse studies have provided unequivocal evidence that the over‐activation of the WNT/β‐catenin signalling pathway underlies the molecular aetiology of these tumours. Recently, research using genetically modified mouse models of human ACP have revealed a critical and unexpected non‐cell autonomous role for pituitary stem cells in ACP tumourigenesis, which has expanded the cancer stem cell paradigm. As the result of this basic research, the pathogenesis of ACP is being unveiled, with promising implications for the development of novel treatments against these childhood neoplasms. These benign tumours may additionally represent a unique model to provide insights into the initial steps of oncogenesis.
The Visual Role of Objects' Facing Surfaces
Authors: Mcneill William E. S.
Published: January 2015

It is often assumed that when we see common opaque objects in standard light this is in virtue of seeing their facing surfaces. Here I argue that we should reject that claim. Either we don't see objects' facing surfaces, or—if we hold on to the claim that we do see such things—it is at least not in virtue of seeing them that we see common opaque objects. I end by showing how this conclusion squares both with our intuitions and with the facts of vision science.
X monosomy in a Virilized Female Cat
Authors: Szczerbal I , Nizanski W , Dzimira S , Nowacka‐Woszuk J , Ochota M , Switonski M
Published: January 2015

Contents

An infertile Siamese female cat was subjected for clinical, histological, cytogenetic and molecular studies due to ambiguous external genitalia (vulva, vagina, rudimentary penis and scrotum‐like structure) and masculine behaviour. An elevated oestrogen activity and a detectable level of testosterone were found. The cat underwent laparotomy. The gonads and the uterus were removed and subjected for histological studies, which showed ovaries with corpora lutea and a some primordial follicles. Chromosome studies of lymphocyte and fibroblast cultures, with the use of Giemsa staining, G‐banding and whole X chromosome painting by fluorescence in situ hybridization, revealed pure X monosomy. Molecular analysis showed the absence of the SRY gene. Our study revealed for the first time that X monosomy in cats may be associated with virilization, in spite of the lack of the SRY gene.
A Numerical Method for Computing Time‐Periodic Solutions in Dissipative Wave Systems
Authors: Yang Jianke
Published: January 2015

A numerical method is proposed for computing time‐periodic and relative time‐periodic solutions in dissipative wave systems. In such solutions, the temporal period, and possibly other additional internal parameters such as the propagation constant, are unknown priori and need to be determined along with the solution itself. The main idea of the method is to first express those unknown parameters in terms of the solution through quasi‐Rayleigh quotients, so that the resulting integrodifferential equation is for the time‐periodic solution only. Then this equation is computed in the combined spatiotemporal domain as a boundary value problem by Newton‐conjugate‐gradient iterations. The proposed method applies to both stable and unstable time‐periodic solutions; its numerical accuracy is spectral; it is fast‐converging; its memory use is minimal; and its coding is short and simple. As numerical examples, this method is applied to the Kuramoto–Sivashinsky equation and the cubic‐quintic Ginzburg–Landau equation, whose time‐periodic or relative time‐periodic solutions with spatially periodic or spatially localized profiles are computed. This method also applies to systems of ordinary differential equations, as is illustrated by its simple computation of periodic orbits in the Lorenz equations. MATLAB codes for all numerical examples are provided in the Appendices to illustrate the simple implementation of the proposed method.
The role of social support in the acculturation and mental health of unaccompanied minor asylum seekers
Authors: Oppedal Brit , Idsoe Thormod
Published: January 2015

There is a lack of knowledge about psychosocial resources that may sustain post‐resettlement psychological adjustment among unaccompanied minor asylum‐seekers. The aim of this study is to investigate the impact of social support from family abroad and friends on acculturation, discrimination, and mental health among these vulnerable children and youth. Questionnaire data were collected from a population‐based multi‐ethnic sample involving 895 unaccompanied minors resettled in municipalities in all regions of the country. They met in groups in their local communities. The informants were on average 18.6 years, and had an average length of stay in Norway of 3.5 years. The findings showed that the participants suffered from high levels of ongoing war related intrusive symptoms and depression. Still, at the same time they engaged in adaptation processes that are normative to youth with immigrant backgrounds, in terms of constructing supportive networks and developing culture competence. In accordance with the main effect hypothesis, social support had direct effects on depression and indirect effects by increasing culture competence that may aid the young refugees in dealing with discrimination. However, there were no effects of social support on symptoms of PTSD. The findings give direction to areas of interventions, beyond dealing with the sequel of the traumas the unaccompanied minors have been exposed to, not only for clinicians, but also social workers and school personnel.
The crystalloid‐colloid debate: Consequences of resuscitation fluid selection in veterinary critical care
Authors: Cazzolli Dava , Prittie Jennifer
Published: January 2015

Objective

To provide a comprehensive review of the current literature in human and veterinary medicine evaluating the impact of resuscitation fluid choice on patient outcome and adverse effects.

Data Sources

Prospective and retrospective studies, experimental models, and review articles in both human and veterinary medicine retrieved via PubMed.

Human Data Synthesis

A series of recent, large, randomized controlled trials in critically ill human patients comparing crystalloid versus colloid driven fluid resuscitation algorithms have demonstrated no outcome benefit with the use of natural or synthetic colloids. Synthetic colloidal solutions are associated with an increased incidence of adverse effects including acute kidney injury, need for renal replacement therapy, and coagulopathies. Further, colloidal solutions demonstrate a larger volume of distribution in the setting of critical illness than hypothesized. These findings have created controversy regarding colloid fluid resuscitation in critically ill patients and challenge current resuscitation strategies. A thorough review of the most influential human data is provided.

Veterinary Data Synthesis

No veterinary clinical outcome data pertaining to fluid resuscitation choice currently exist. Veterinary data from experimental and small clinical trials evaluating the coagulopathic effects of hydroxyethyl starch solutions are described. Data pertaining to the use of natural colloids and albumin products in clinical veterinary patients are reviewed. In addition, data pertaining to the comparative intravascular volume expansion effectiveness of different fluid types in canine patients are reviewed.

Conclusions

Clinical data from critically ill human patients have failed to demonstrate an outcome advantage associated with colloidal fluid resuscitation and indicate that hydroxyethyl starch solutions may be associated with significant adverse effects, including acute kidney injury, need for renal replacement therapy, coagulopathies, and pathologic tissue uptake. The ability to apply these findings to veterinary patients is unknown; however, similar pathophysiology may apply, and critical re‐evaluation of resuscitation strategies is justified.