bluuebunny/crossref_metadata_2025 huggingface dataset:
12 The Mexican Legacy in Nicaragua, or Problems when Data Behave Badly
Authors: McCafferty Geoffrey
Published: May 2015

Investigations over the past 15 years have sought archaeological evidence for Mexican migrants to Pacific Nicaragua, as indicated in ethnohistorical origin myths and as embraced by contemporary popular culture. Extensive excavations at three Postclassic sites have provided evidence of domestic architecture, foodways, mortuary remains, and religious practices—all considered to be potential archaeological indicators of ethnicity, but none of which provide strong evidence of Mexican identity. A larger theme is the contemporary reaction to challenging the identity of the indigenous ancestors. This paper discusses the Mexican legacy in Nicaragua, and strategies for negotiating popular ideology with badly behaved archaeological data.
Development and analysis of furazolidone‐resistant Escherichia coli mutants
Authors: Martínez‐Puchol Sandra , Gomes Cláudia , Pons Maria J. , Ruiz‐Roldán Lidia , Torrents de la Peña Alba , Ochoa Theresa J. , Ruiz Joaquim
Published: May 2015

Furazolidone‐resistant mutants were obtained from four clinical isolates of diarrhoeagenic Escherichia coli. The stability of the resistance and the frequency of mutation were established. The minimal inhibitory concentration of furazolidone, nitrofurantoin, nalidixic acid, ampicillin, chloramphenicol and tetracycline was established both in the presence and absence of the efflux pump inhibitor Phe‐Arg‐β‐Naphtylamyde. The presence of mutations in the nitroreductase genes nfsA and nfsB was analysed by PCR; sequencing and their enzymatic activity was assessed by a spectrophotometric assay. Alterations in outer membrane proteins were studied by SDS‐PAGE. The frequency of mutation ranged from <9.6 × 10−10 to 9.59 × 10−7. Neither an effect on efflux pumps inhibited by Phe‐Arg‐β‐Naphtylamyde nor cross‐resistance with the antibiotics studied was observed. Nineteen mutants (52.94%) presented mutations in the nitroreductase‐encoding genes: 17 in the nfsA gene (15 mutants with an internal stop codon, 2 with amino acid changes), 2 in the nfsB (all amino acid changes). Alterations in the outer membrane proteins OmpA and OmpW were also observed. Although more studies are necessary to find other resistance mechanisms, present data showed the low potential of selecting furazolidone‐resistant mutants, together with the lack of cross‐resistance with unrelated antimicrobial agents.
How to evaluate PCR assays for the detection of low‐level DNA
Authors: Clausen Frederik Banch , Urhammer Emil , Rieneck Klaus , Krog Grethe Risum , Nielsen Leif Kofoed , Dziegiel Morten Hanefeld
Published: May 2015

High sensitivity of PCR‐based detection of very low copy number DNA targets is crucial. Much focus has been on design of PCR primers and optimization of the amplification conditions. Very important are also the criteria used for determining the outcome of a PCR assay, e.g. how many replicates are needed and how many of these should be positive or what amount of template should be used? We developed a mathematical model to obtain a simple tool for quick PCR assay evaluation before laboratory optimization and validation procedures. The model was based on the Poisson distribution and the Binomial distribution describing parameters for singleplex real‐time PCR‐based detection of low‐level DNA. The model was tested against experimental data of diluted cell‐free foetal DNA. Also, the model was compared with a simplified formula to enable easy predictions. The model predicted outcomes that were not significantly different from experimental data generated by testing of cell‐free foetal DNA. Also, the simplified formula was applicable for fast and accurate assay evaluation. In conclusion, the model can be applied for evaluation of sensitivity of real‐time PCR‐based detection of low‐level DNA, and may also assist in design of new assays before standard laboratory optimization and validation is initiated.
Occult vs. overt upper gastrointestinal bleeding – inverse relationship and the use of mucosal damaging and protective drugs
Authors: Taha A. S. , McCloskey C. , Craigen T. , Simpson A. , Angerson W. J.
Published: May 2015

Background

While efforts have focused on the prevention of overt upper gastrointestinal bleeding (UGIB), little is known about occult GIB, which might also originate from sites not protected by acid inhibition.

Aim

To measure the incidence and outcomes of both overt and occult GIB over a 6‐year period (2007–2012), and to assess the use of NSAIDs, anti‐thrombotic therapy (ATT), proton pump inhibitors (PPIs), and iron therapy.

Methods

A sample of 300 patients (100 from each of three index years) with occult GIB was randomly selected and their outcomes were compared with those of patients with overt UGIB (N = 869).

Results

The incidence of overt UGIB fell from 140.1 per 100 000 population per annum in 2007 to 106.8 in 2010 and to 88.0 in 2012 (P < 0.001); while that of occult GIB rose from 243.1 to 263.6 and to 292.8 (P < 0.001) over the same period. The incidence of occult GIB was highly correlated with the number of prescriptions of PPIs per 1000 population (χ2 trend = 11.80; P < 0.001). In the overt UGIB group, the median haemoglobin level on presentation was lowest (10.3) in patients taking NSAIDs/ATT plus PPIs compared with those taking PPIs alone (11.5), NSAIDs/ATT alone (10.4) or none of these drugs (12.7 g/dL) (P < 0.001, Kruskal–Wallis).

Conclusions

An inverse trend seems to have formed in the incidence of overt vs. occult gastrointestinal bleeding in association with the wider use of PPIs and NSAIDs. An alternative approach to acid inhibition is needed to prevent gastrointestinal bleeding.
Non‐Chemotherapy‐Induced Agranulocytosis Detected by a Prospective Pharmacovigilance Program in a Tertiary Hospital
Authors: Medrano‐Casique Nicolás , Tong Hoi Y. , Borobia Alberto M. , Carcas Antonio J. , Frías Jesús , Ramírez Elena
Published: May 2015

We conducted a prospective evaluation of non‐chemotherapy‐induced agranulocytosis (NIA) in a tertiary hospital in Spain. Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital, we detected agranulocytosis cases over a period of 42 consecutive months. This report estimates incidence, drug causality, clinical features and outcomes ofNIAcases and assesses laboratory differences with respect to non‐NIA. We detected 1349 cases of agranulocytosis in 538 adult patients; of these, 43 cases in 40 patients were caused by non‐chemotherapy drugs. The incidence rate for 10,000 patients during the study period was 2.75 [Poisson confidence interval (CI)‐95%: 0.62–7.22]. The mean (S.D.) age was 48 (21) years. All cases were categorized as serious, because they required hospitalization (28 cases) or prolongation of hospitalization (15 cases). The outcome was recovery without sequela (39 cases), recovery with sequela (one case of toe amputation) or death (three cases, 7%). The most frequent cause ofNIAwas antimicrobial drugs (19 cases). The highest incidence rate per 10,000 defined daily doses was for cefepime (83.85; Poisson‐CI95%: 67–102.89). Automatic linear modelling (n = 75,R2 = 77.9%) showed a significant inverse association with platelets, alkaline phosphatase, C‐reactive protein, fibrinogen, lactate dehydrogenase; and direct association with mean corpuscular haemoglobin, and haematocrit. A generalized linear model retained platelets, total serum proteins, creatinine and haemoglobin. The findings suggest an immune‐mediated destruction or myeloid toxicity, possibly facilitated by an increase in drug exposure. There might be additional contributing factors, such as nutritional deficiencies or chronic diseases, to developNIAafter exposure to a potentially causative drug.
An automated essay‐evaluation corpus of English as a Foreign Language writing
Authors: Jiang Yaoyi
Published: May 2015

The Report of Chinese Students' English Writing Ability (2014) focuses on the Chinese students' English writing in the automated essay‐evaluation context. The data and samples are primarily from a national‐wide writing project involving 300 814 English as a Foreign Language participants from 452 schools in China during a period of April 10 to May 10, 2014. Aiming to formulate a liable and detailed description of English writing ability of the target learners, a variety of data were collected and processed by means of dimensional analysis, including the frequency vocabulary and collocation, average length of vocabulary, sentence and essay, average number of paragraph, vocabulary richness, density of subordinate clause, most frequent errors, etc. In addition, background information of the participants was also solicited. The corpus‐based analysis is still ongoing, and some results have already revealed meaningful trend and characteristics in the writing of Chinese students. Also, the observation of participants' learning behavior signifies meaningful implications for future automated essay‐evaluation projects.
Brokering Sexual Orientation and Gender Identity: Chilean Lawyers and Public Interest Litigation Strategies
Authors: MILES PENNY
Published: May 2015

Rights gains for members of lesbian, gay, bisexual, transgender and intersex (LGBTI) populations in Chile have been highly contentious since democratisation, indicative of the stigmatisation directed towards non‐normative gender and sexual identities. This article addresses the role of activist lawyers pursuingLGBTIrights cases through the courts, and draws onMcAdamand colleagues' (2001) concept of a ‘broker’ to examine the lawyers' roles in linking previously unconnected sites within the judiciary and further afield. The analysis draws these processes together through interactionist perspectives of meaning‐making and how they relate to stigma, deviancy and identity.
New selective inhibitors of calcium‐activated chloride channels – T16Ainh‐A01, CaCCinh‐A01 and MONNA – what do they inhibit?
Authors: Boedtkjer D M B , Kim S , Jensen A B , Matchkov V M , Andersson K E
Published: May 2015

Background and Purpose

T16Ainh‐A01, CaCCinh‐A01 and MONNA are identified as selective inhibitors of the TMEM16A calcium‐activated chloride channel (CaCC). The aim of this study was to examine the chloride‐specificity of these compounds on isolated resistance arteries in the presence and absence (±) of extracellular chloride.

Experimental Approach

Isolated resistance arteries were maintained in a myograph and tension recorded, in some instances combined with microelectrode impalement for membrane potential measurements or intracellular calcium monitoring using fura‐2. Voltage‐dependent calcium currents (VDCC) were measured in A7r5 cells with voltage‐clamp electrophysiology using barium as a charge carrier.

Key Results

Rodent arteries preconstricted with noradrenaline or U46619 were concentration‐dependently relaxed by T16Ainh‐A01 (0.1–10 μM): IC50 and maximum relaxation were equivalent in ±chloride (30 min aspartate substitution) and the T16Ainh‐A01‐induced vasorelaxation ±chloride were accompanied by membrane hyperpolarization and lowering of intracellular calcium. However, agonist concentration–response curves ±chloride, with 10 μM T16Ainh‐A01 present, achieved similar maximum constrictions although agonist‐sensitivity decreased. Contractions induced by elevated extracellular potassium were concentration‐dependently relaxed by T16Ainh‐A01 ±chloride. Moreover, T16Ainh‐A01 inhibited VDCCs in A7r5 cells in a concentration‐dependent manner. CaCCinh‐A01 and MONNA (0.1–10 μM) induced vasorelaxation ±chloride and both compounds lowered maximum contractility. MONNA, 10 μM, induced substantial membrane hyperpolarization under resting conditions.

Conclusions and Implications

T16Ainh‐A01, CaCCinh‐A01 and MONNA concentration‐dependently relax rodent resistance arteries, but an equivalent vasorelaxation occurs when the transmembrane chloride gradient is abolished with an impermeant anion. These compounds therefore display poor selectivity for TMEM16A and inhibition of CaCC in vascular tissue in the concentration range that inhibits the isolated conductance.
Validating the GTP‐cyclohydrolase 1‐feedback regulatory complex as a therapeutic target using biophysical and in vivo approaches
Authors: Hussein D , Starr A , Heikal L , McNeill E , Channon K M , Brown P R , Sutton B J , McDonnell J M , Nandi M
Published: May 2015

Background and Purpose

6R‐L‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide biosynthesis. Substantial clinical evidence indicates that intravenous BH4 restores vascular function in patients. Unfortunately, oral BH4 has limited efficacy. Therefore, orally bioavailable pharmacological activators of endogenous BH4 biosynthesis hold significant therapeutic potential. GTP‐cyclohydrolase 1 (GCH1), the rate limiting enzyme in BH4 synthesis, forms a protein complex with GCH1 feedback regulatory protein (GFRP). This complex is subject to allosteric feed‐forward activation by L‐phenylalanine (L‐phe). We investigated the effects of L‐phe on the biophysical interactions of GCH1 and GFRP and its potential to alter BH4 levels in vivo.

Experimental Approach

Detailed characterization of GCH1–GFRP protein–protein interactions were performed using surface plasmon resonance (SPR) with or without L‐phe. Effects on systemic and vascular BH4 biosynthesis in vivo were investigated following L‐phe treatment (100 mg·kg−1, p.o.).

Key Results

GCH1 and GFRP proteins interacted in the absence of known ligands or substrate but the presence of L‐phe doubled maximal binding and enhanced binding affinity eightfold. Furthermore, the complex displayed very slow association and dissociation rates. In vivo, L‐phe challenge induced a sustained elevation of aortic BH4, an effect absent in GCH1(fl/fl)‐Tie2Cre mice.

Conclusions and Implications

Biophysical data indicate that GCH1 and GFRP are constitutively bound. In vivo, data demonstrated that L‐phe elevated vascular BH4 in an endothelial GCH1 dependent manner. Pharmacological agents which mimic the allosteric effects of L‐phe on the GCH1–GFRP complex have the potential to elevate endothelial BH4 biosynthesis for numerous cardiovascular disorders.
Early Behavioral Inhibition and Emotion Regulation: Pathways Toward Social Competence in Middle Childhood
Authors: Penela Elizabeth C. , Walker Olga L. , Degnan Kathryn A. , Fox Nathan A. , Henderson Heather A.
Published: May 2015

This study examined emotion regulation (ER) as a mediator in the relation between early behavioral inhibition (BI) and later social competence (N = 257), and whether this mediation varied depending on BI levels. Maternal report and observational measures were used to assess BI (ages 2 and 3). Children's ER strategies (age 5) and social competence with an unfamiliar peer (age 7) were measured using observational measures. Results showed that BI predicted less engaged ER strategies during a disappointment task, and engaged ER predicted higher social competence. Engaged ER mediated the effect of BI on social competence, but only for highly inhibited children. Findings elucidate developmental trajectories of risk and resilience, and suggest targeting regulatory strategies in early prevention efforts with highly inhibited children.
Moderately impaired renal function increases morning cortisol and cortisol levels at dexamethasone suppression test in patients with incidentally detected adrenal adenomas
Authors: Olsen Henrik , Mjöman Mattias
Published: May 2015

Objective

Patients with incidentally detected adrenal adenomas may have subclinical hypercortisolism. We hypothesized that impaired renal function could lead to increased cortisol levels in these patients.

Design

Descriptive retrospective study of consecutive patients.

Patients

A total of 166 patients with incidentally detected unilateral adrenal adenomas were examined during 2008–2013.

Measurements

Levels of cortisol, ACTH and cortisol at 1 mg overnight dexamethasone suppression test (DST) were measured. The estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation.

Results

Renal function was normal, mildly impaired, moderately impaired or severely impaired (eGFR >90, 60–90, 30–60 and 15–30 ml/min/1·73 m2) in 34, 54, 10 and 1% of the patients, respectively. Patients with normal and mildly impaired renal function had similar cortisol levels. Patients with moderately impaired renal function, compared to all the patients with eGFR >60 ml/min/1·73 m2, exhibited increased cortisol (541 vs 456 nmol/l, P = 0·02), increased cortisol at DST (62 vs 37 nmol/l, P = 0·001), but similar ACTH levels (4·1 vs 2·9 pmol/l, P = 0·21). Patients with moderately impaired renal function thus exhibited cortisol at DST ≥50 nmol/l, more often than patients with eGFR >60 ml/min/1·73 m2 (76% vs 30%, P = 0·000), while the prevalence of ACTH below 2 pmol/l was similar (24% vs 31%, P = 0·51).

Conclusions

Moderately impaired renal function increases cortisol and cortisol at DST in patients with adrenal adenomas, while mildly impaired renal function has no such effect. Cortisol level at DST ≥50 nmol/l therefore seems to have low specificity in diagnosing subclinical adrenal hypercortisolism, and an additional criterion, for example low ACTH, is required.
Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee
Authors: Okosieme Onyebuchi , Gilbert Jackie , Abraham Prakash , Boelaert Kristien , Dayan Colin , Gurnell Mark , Leese Graham , McCabe Christopher , Perros Petros , Smith Vicki , Williams Graham , Vanderpump Mark
Published: May 2015

The management of primary hypothyroidism with levothyroxine (L‐T4) is simple, effective and safe, and most patients report improved well‐being on initiation of treatment. However, a proportion of individuals continue to suffer with symptoms despite achieving adequate biochemical correction. The management of such individuals has been the subject of controversy and of considerable public interest. The American Thyroid Association (ATA) and the European Thyroid Association (ETA) have recently published guidelines on the diagnosis and management of hypothyroidism. These guidelines have been based on extensive reviews of the medical literature and include sections on the role of combination therapy with L‐T4 and liothyronine (L‐T3) in individuals who are persistently dissatisfied with L‐T4 therapy. This position statement by the British Thyroid Association (BTA) summarises the key points in these guidelines and makes recommendations on the management of primary hypothyroidism based on the current literature, review of the published positions of the ETA and ATA, and in line with best principles of good medical practice. The statement is endorsed by the Association of Clinical Biochemistry, (ACB), British Thyroid Foundation, (BTF), Royal College of Physicians (RCP) and Society for Endocrinology (SFE).
Apoptotic and autophagic pathways with relevant small‐molecule compounds, in cancer stem cells
Authors: Zhang Lan , Tong Xupeng , Li Jingjing , Huang Yue , Hu Xinyue , Chen Yi , Huang Jian , Wang Jinhui , Liu Bo
Published: May 2015

Accumulating evidence demonstrates existence of cancer stem cells (CSCs), which are suspected of contributing to cancer cell self‐renewal capacity and resistance to radiation and/or chemotherapy. Including evasion of apoptosis and autophagic cell death, CSCs have revealed abilities to resist cell death, making them appealing targets for cancer therapy. Recently, molecular mechanisms of apoptosis and of autophagy in CSCs have been gradually explored, comparing them in stem cells and in cancer cells; distinct expression of these systems in CSCs may elucidate how these cells exert their capacity of unlimited self‐renewal and hierarchical differentiation. Due to their proposed ability to drive tumour initiation and progression, CSCs may be considered to be potentially useful pharmacological targets. Further, multiple compounds have been verified as triggering apoptosis and/or autophagy, suppressing tumour growth, thus providing new strategies for cancer therapy. In this review, we summarized regulation of apoptosis and autophagy in CSCs to elucidate how key proteins participate in control of survival and death; in addition, currently well‐studied compounds that target CSC apoptosis and autophagy are selectively presented. With increasing attention to CSCs in cancer therapy, researchers are now trying to find responses to unsolved questions as unambiguous as possible, which may provide novel insight into future anti‐cancer regimes.
Differential antigen expression and aberrant signaling via PI3/AKT, MAP/ERK, JAK/STAT, and Wnt/β catenin pathways in Lin−/CD38−/CD34+ cells in acute myeloid leukemia
Authors: Garg Swati , Shanmukhaiah Chandrakala , Marathe Supreet , Mishra Prashant , Babu Rao Vunditi , Ghosh Kanjaksha , Madkaikar Manisha
Published: May 2015

Acute myeloid leukemia is often called as stem cell disease that presents with treatment failure and poor disease outcome. Leukemic stem cells in acute myeloid leukemia (AML) are enriched in Lineage‐/CD38−/CD34+ compartment of CD34−positive AML. Many markers important for stem cell biology have been reported for their association with leukemic stem cell population, but what remains clinically most important is a rapid identification of prognostic information. In this study, we evaluated four signal transduction pathways and thirteen markers on Lin−/CD38−/CD34+ population in AML. Expressions were compared in different AML subtypes, survival, and treatment outcome groups. We observed that markers important in homing, cell quiescence, and signal propagation such as CD44, CD96, CD90, WT‐1, CD123 and CD25 were most significantly differentially expressed on Lin‐/CD38−/CD34+ population in AML from their normal counterparts (P < 0.05, Mann–Whitney). Constitutive activation of phospho ERK, AKT, and STAT5 in these cells was associated with poor outcome. Also, an increased frequency of putative leukemic stem cell population shows negative impact on treatment outcome and overall survival, suggesting that initial evaluation of AML samples for pLSC frequency and constitutively activated signaling pathway can provide prognostic and therapeutic information at the time of diagnosis.
Inhibitory short‐term plasticity modulates neuronal activity in the rat entopeduncular nucleus in vitro
Authors: Lavian Hagar , Korngreen Alon
Published: May 2015

The entopeduncular nucleus (EP) is one of the basal ganglia output nuclei integrating synaptic information from several pathways within the basal ganglia. The firing of EP neurons is modulated by two streams of inhibitory synaptic transmission, the direct pathway from the striatum and the indirect pathway from the globus pallidus. These two inhibitory pathways continuously modulate the firing of EP neurons. However, the link between these synaptic inputs to neuronal firing in the EP is unclear. To investigate this input–output transformation we performed whole‐cell and perforated‐patch recordings from single neurons in the entopeduncular nucleus in rat brain slices during repetitive stimulation of the striatum and the globus pallidus at frequencies within the in vivo activity range of these neurons. These recordings, supplemented by compartmental modelling, showed that GABAergic synapses from the striatum, converging on EP dendrites, display short‐term facilitation and that somatic or proximal GABAergic synapses from the globus pallidus show short‐term depression. Activation of striatal synapses during low presynaptic activity decreased postsynaptic firing rate by continuously increasing the inter‐spike interval. Conversely, activation of pallidal synapses significantly affected postsynaptic firing during high presynaptic activity. Our data thus suggest that low‐frequency striatal output may be encoded as progressive phase shifts in downstream nuclei of the basal ganglia while high‐frequency pallidal output may continuously modulate EP firing.
Crop rotational diversity enhances belowground communities and functions in an agroecosystem
Authors: Tiemann L. K. , Grandy A. S. , Atkinson E. E. , Marin‐Spiotta E. , McDaniel M. D.
Published: May 2015

Biodiversity loss, an important consequence of agricultural intensification, can lead to reductions in agroecosystem functions and services. Increasing crop diversity through rotation may alleviate these negative consequences by restoring positive aboveground–belowground interactions. Positive impacts of aboveground biodiversity on belowground communities and processes have primarily been observed in natural systems. Here, we test for the effects of increased diversity in an agroecosystem, where plant diversity is increased over time through crop rotation. As crop diversity increased from one to five species, distinct soil microbial communities were related to increases in soil aggregation, organic carbon, total nitrogen, microbial activity and decreases in the carbon‐to‐nitrogen acquiring enzyme activity ratio. This study indicates positive biodiversity–function relationships in agroecosystems, driven by interactions between rotational and microbial diversity. By increasing the quantity, quality and chemical diversity of residues, high diversity rotations can sustain soil biological communities, with positive effects on soil organic matter and soil fertility.
To follow or not? How animals in fusion–fission societies handle conflicting information during group decision‐making
Authors: Merkle Jerod A. , Sigaud Marie , Fortin Daniel
Published: May 2015

When group members possess differing information about the environment, they may disagree on the best movement decision. Such conflicts result in group break‐ups, and are therefore a fundamental driver of fusion–fission group dynamics. Yet, a paucity of empirical work hampers our understanding of how adaptive evolution has shaped plasticity in collective behaviours that promote and maintain fusion–fission dynamics. Using movement data fromGPS‐collared bison, we found that individuals constantly associated with other animals possessing different spatial knowledge, and both personal and conspecific information influenced an individual's patch choice decisions. During conflict situations, bison used group familiarity coupled with their knowledge of local foraging options and recently sampled resource quality when deciding to follow or leave a group – a tactic that led to energy‐rewarding movements. Natural selection has shaped collective behaviours for coping with social conflicts and resource heterogeneity, which maintain fusion–fission dynamics and play an essential role in animal distribution.
Transcriptional control of late differentiation in human keratinocytes by TAp63 and Notch
Authors: Koh Li Fang , Ng Boon Kiat , Bertrand Juliette , Thierry Françoise
Published: May 2015

We previously showed that in cervical carcinoma cells, the TAp63β isoform of the p63 transcription factor is negatively interfering with the carcinogenic pathways promoting anchorage‐independent growth. In this study, we have defined the mechanisms underlying the effects of TAp63β through a transcriptome analysis of human keratinocytes overexpressing this protein. TAp63β modulated expression of 1203 genes (944 activated and 259 repressed; P‐value <0.05), notably genes involved in epithelial development and keratinocyte differentiation. In comparison, while TAp63γ acts similarly to TAp63β to transactivate a selected panel of target genes, other p63 isoforms, including ΔNp63α, which is highly expressed in keratinocytes, are inactive. Upon induction of differentiation of primary human keratinocytes, we observed endogenous expression of TAp63β and γ isoforms, along with transcriptional activation of selected target genes. Intriguingly, our data also indicated that TAp63β activates transcription of members of the Notch pathway, which is known to promote keratinocyte differentiation. By inhibiting and activating the Notch pathway, we revealed a subset of TAp63β‐activated genes that were co‐dependent on Notch for their expression. Our work demonstrates that the shorter TAp63 isoforms (TAp63β/γ) are specifically induced in human keratinocytes and cooperate with Notch signalling to activate transcription of late differentiation genes supporting their role as putative tumor suppressors in HPV‐associated tumorigenesis.
Towards a global assessment of pyrogenic carbon from vegetation fires
Authors: Santín Cristina , Doerr Stefan H. , Kane Evan S. , Masiello Caroline A. , Ohlson Mikael , de la Rosa Jose Maria , Preston Caroline M. , Dittmar Thorsten
Published: May 2015

The production of pyrogenic carbon (PyC; a continuum of organic carbon (C) ranging from partially charred biomass and charcoal to soot) is a widely acknowledged C sink, with the latest estimates indicating that ~50% of the PyC produced by vegetation fires potentially sequesters C over centuries. Nevertheless, the quantitative importance of PyC in the global C balance remains contentious, and therefore, PyC is rarely considered in global C cycle and climate studies. Here we examine the robustness of existing evidence and identify the main research gaps in the production, fluxes and fate of PyC from vegetation fires. Much of the previous work on PyC production has focused on selected components of total PyC generated in vegetation fires, likely leading to underestimates. We suggest that global PyC production could be in the range of 116–385 Tg C yr−1, that is ~0.2–0.6% of the annual terrestrial net primary production. According to our estimations, atmospheric emissions of soot/black C might be a smaller fraction of total PyC (<2%) than previously reported. Research on the fate of PyC in the environment has mainly focused on its degradation pathways, and its accumulation and resilience either in situ (surface soils) or in ultimate sinks (marine sediments). Off‐site transport, transformation and PyC storage in intermediate pools are often overlooked, which could explain the fate of a substantial fraction of the PyC mobilized annually. We propose new research directions addressing gaps in the global PyC cycle to fully understand the importance of the products of burning in global C cycle dynamics.
Association mapping in Salix viminalis L. (Salicaceae) – identification of candidate genes associated with growth and phenology
Authors: Hallingbäck Henrik R. , Fogelqvist Johan , Powers Stephen J. , Turrion‐Gomez Juan , Rossiter Rachel , Amey Joanna , Martin Tom , Weih Martin , Gyllenstrand Niclas , Karp Angela , Lagercrantz Ulf , Hanley Steven J. , Berlin Sofia , Rönnberg‐Wästljung Ann‐Christin
Published: May 2015

Willow species (Salix) are important as short‐rotation biomass crops for bioenergy, which creates a demand for faster genetic improvement and breeding through deployment of molecular marker‐assisted selection (MAS). To find markers associated with important adaptive traits, such as growth and phenology, for use in MAS, we genetically dissected the trait variation of a Salix viminalis (L.) population of 323 accessions. The accessions were sampled throughout northern Europe and were established at two field sites in Pustnäs, Sweden, and at Woburn, UK, offering the opportunity to assess the impact of genotype‐by‐environment interactions (G × E) on trait–marker associations. Field measurements were recorded for growth and phenology traits. The accessions were genotyped using 1536 SNP markers developed from phenology candidate genes and from genes previously observed to be differentially expressed in contrasting environments. Association mapping between 1233 of these SNPs and the measured traits was performed taking into account population structure and threshold selection bias. At a false discovery rate (FDR) of 0.2, 29 SNPs were associated with bud burst, leaf senescence, number of shoots or shoot diameter. The percentage of accession variation () explained by these associations ranged from 0.3% to 4.4%, suggesting that the studied traits are controlled by many loci of limited individual impact. Despite this, a SNP in the EARLY FLOWERING 3 gene was repeatedly associated (FDR < 0.2) with bud burst. The rare homozygous genotype exhibited 0.4–1.0 lower bud burst scores than the other genotype classes on a five‐grade scale. Consequently, this marker could be promising for use in MAS and the gene deserves further study. Otherwise, associations were less consistent across sites, likely due to their small estimates and to considerable G × E interactions indicated by multivariate association analyses and modest trait accession correlations across sites (0.32–0.61).
Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been …
Authors: Baron Eric P.
Published: May 2015

Background

The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine. Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science. However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research. Almost half of the United States has now legalized medicinal cannabis, several states have legalized recreational use, and others have legalized cannabidiol‐only use, which is one of many therapeutic cannabinoids extracted from cannabis. Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is some intriguing supportive evidence.

Objective

To review the history of medicinal cannabis use, discuss the pharmacology and physiology of the endocannabinoid system and cannabis‐derived cannabinoids, perform a comprehensive literature review of the clinical uses of medicinal cannabis and cannabinoids with a focus on migraine and other headache disorders, and outline general clinical practice guidelines.

Conclusion

The literature suggests that the medicinal use of cannabis may have a therapeutic role for a multitude of diseases, particularly chronic pain disorders including headache. Supporting literature suggests a role for medicinal cannabis and cannabinoids in several types of headache disorders including migraine and cluster headache, although it is primarily limited to case based, anecdotal, or laboratory‐based scientific research. Cannabis contains an extensive number of pharmacological and biochemical compounds, of which only a minority are understood, so many potential therapeutic uses likely remain undiscovered. Cannabinoids appear to modulate and interact at many pathways inherent to migraine, triptan mechanisms ofaction, and opiate pathways, suggesting potential synergistic or similar benefits. Modulation of the endocannabinoid system through agonism or antagonism of its receptors, targeting its metabolic pathways, or combining cannabinoids with other analgesics for synergistic effects, may provide the foundation for many new classes of medications. Despite the limited evidence and research suggesting a role for cannabis and cannabinoids in some headache disorders, randomized clinical trials are lacking and necessary for confirmation and further evaluation.
Effect of knowledge on decision making in the context of organic cotton clothing
Authors: Oh Keunyoung , Abraham Liza
Published: May 2015

This research was designed to study whether consumer knowledge on organic cotton and relevant issues influences attitude toward and price acceptance of organic cotton clothing. The effect of consumer knowledge was also studied on the way consumers use product label information in purchasing organic cotton clothing. An online survey was developed to measure the variables including experimental choice‐based conjoint models for mandatory and auxiliary label specifications. Four hundred ninety‐eight people completed the survey. The results indicated that moderately and highly knowledgeable participants were more willing to buy organic cotton clothing at higher price points and they had more positive attitudes toward organic cotton clothing than low knowledgeable participants. The results suggest that differentially knowledgeable consumers may attend to different types of information provided on product labels to evaluate organic cotton apparel products. Providing product‐related information on product labels is essential; however, providing additional information on the benefits of using organic cotton and socially responsible business practices may improve consumers’ knowledge and acceptability of organic cotton apparel products.
Evaluation of small‐volume tubes for venous and capillary PT (INR) samples
Authors: Onelöv L. , Basmaji R. , Svensson A. , Nilsson M. , Antovic J. P.
Published: May 2015

Introduction

Frequent PT (INR) testing may represent a problem for patients on warfarin treatment, and capillary or small‐volume tubes may be more appropriate for such patients. A demand for small‐volume tubes also comes from pediatric wards. Yet, while various small‐volume tubes are available, they have not been properly evaluated.

Methods

Three small‐volume tubes were tested (MiniCollect 3.8% citrate, MiniCollect 3.2% citrate and Microvette EDTA) and compared with a standard 4.5‐mL 3.2% citrated tube. Samples were taken by venipuncture from the back of the hand and by capillary sampling from the tip of the finger. The measures were compared with those after standard venipuncture of the arm fold. A total of 180 samples, using different combinations of tubes and sampling sites, were collected from 30 volunteers.

Results

There were no differences in the results obtained using citrate tubes for venous samples in comparison with those obtained by standard sampling, while the results when using EDTA tubes were not comparable to those obtained by standard sampling (P < 0.001), expressing systematically lower values (by about 10%). The results observed after capillary sampling were significantly different to those obtained after standard sampling.

Conclusions

The MiniCollect 3.2% tube may be used for PT (INR) venipuncture samples when withdrawal of a small amount of blood is preferable, while EDTA tubes should not be used for PT (INR) testing.
Prospective and randomised evaluation of the protease‐modulating effect of oxidised regenerated cellulose/collagen matrix treatment in pressure sore ulcers
Authors: Kloeters Oliver , Unglaub Frank , de Laat Erik , van Abeelen Marjolijn , Ulrich Dietmar
Published: May 2015

In chronic wounds, excess levels and activity of proteases such as elastase and plasmin have been detected. Oxidised regenerated cellulose/collagen matrix (ORC/collagen matrix) has been reported to ameliorate the wound microenvironment by binding and inactivating excess proteases in wound exudates. In this study, the levels and activity of elastase and plasmin in wound exudates of pressure sore ulcers were measured to determine the beneficial effect of ORC/collagen matrix treatment compared with control treatment with a foam dressing. A total of 33 patients with pressure sores were enrolled in the study and were followed up for 12 weeks after treatment. Ten control patients were treated with a foam hydropolymer dressing (TIELLE®, Systagenix), and the remaining 23 patients were treated with ORC/collagen matrix plus the foam dressing (TIELLE®, Systagenix) on top. Wound assessments were carried out over 12 weeks on a weekly basis, with dressing changes twice a week. Ulcers were photographed and wound exudates were collected on admission and at days 5, 14 and then every 14 days to provide a visual record of any changes in appearance of the ulcer and healing rate and for biochemical analysis of the wound. The levels and activity of elastase and plasmin were measured in wound exudates. Statistical analysis was performed using ANOVA and Bonferroni's post hoc test with P‐values <0·05 considered to be significant. Compared with controls, ORC/collagen matrix–treated pressure sore wounds showed a significant faster healing rate, which positively correlated with a decreased activity of elastase and plasmin in wound exudates. No signs of infection or intolerance to the ORC/collagen matrix were observed.
Clinical recommendations and practical guide for negative pressure wound therapy with instillation
Authors: Gupta Subhas , Gabriel Allen , Lantis John , Téot Luc
Published: May 2015

Effective wound management involves a comprehensive assessment of the patient and the wound to determine an optimal wound treatment plan. It is critical to identify and address factors that may impair wound healing, prior to selecting the most appropriate therapy for each patient. Negative pressure wound therapy (NPWT) is a well‐established advanced therapy that has been successful in adjunctive management of acute and chronic wounds. In recent years, the introduction of topical wound solution delivery in combination with NPWT has provided further benefits to wound healing. A commercially available system now offers automated, volumetric control of instilled topical wound solutions with a dwell time in combination with NPWT (NPWTi‐d; V.A.C. VeraFlo™ Therapy, KCI, an Acelity company, San Antonio, TX). This NPWTi‐d system differs from other instillation systems in that a timed, predetermined volume of topical wound solution is intermittently delivered (versus continuously fed) and allowed to dwell in the wound bed (without NPWT), for a user‐selected period of time before NPWT is resumed. This added accuracy and process simplification of solution delivery in tandem with NPWT have prompted use of NPWTi‐d as first‐line therapy in a wider subset of complex wounds. However, considerably more research is required to validate efficacy of NPWTi‐d in various wound types. The purpose of this review is to provide a relevant overview of wound healing, describe current literature supporting the adjunctive use of NPWTi‐d, propose a clinical approach for appropriate application of NPWTi‐d and conclude with case studies demonstrating successful use of NPWTi‐d. Based on this review, we conclude that either a large case series examining effects of NPWTi‐d on different wound types or possibly a large prospective registry evaluating NPWTi‐d with real‐world topical wound solutions versus immediate debridement and closure would be valuable to the medical community in evaluating the efficacy of this promising therapy.
High‐Temperature Dielectric Relaxations in LiF Single Crystals
Authors: Wang Jing , Wang Chunchang , Li Qiuju , Yu Yi , Zhang Jian , Zheng Jun , Cheng Chao , Li Yide , Wang Hong
Published: May 2015

By means of dielectric permittivity, electric modulus and impedance, the dielectric properties of LiF single crystals were investigated in the temperature range of 30°C–800°C and frequency range of 50 Hz–10 MHz. Two thermally activated relaxations, R1 and R2, were observed. The relaxation R1 showing activation energy around 0.8 eV was found to be related to the Li‐ion diffusion in the crystal. The relaxation R2 contains three Arrhenius segments, the low‐, mid‐, and high‐T segments, separated by boundary temperatures of 325°C and 425°C. These segments in the order of ascending temperature were found to be associated with F3, F3+ centers, F2 centers, and F centers, respectively.
Alternative health eating index and the Dietary Guidelines from American Diabetes Association both may reduce the risk of cardiovascular disease in type 2 diabetes patients
Authors: Wu Pei‐Yu , Huang Chen‐Ling , Lei Weng‐Seng , Yang Shwu‐Huey
Published: May 2015

Background

In the general population, a higher Alternate Healthy Eating Index (AHEI)‐2010 score is related to decreased cardiovascular disease (CVD) risk. Few studies have described the dietary patterns that reduce the risk of CVD or coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM) patients. In the present study, the association between the American Diabetes Association (ADA)‐recommended dietary pattern, AHEI‐2010 , and CVD risk factors and the CVD incidence over 52 months in T2DM patients was evaluated.

Methods

The ADA score was developed from the ADA dietary recommendations. In this prospective study, the 24‐h dietary recall of 124 adult T2DM patients without nephropathy or chronic kidney disease was collected. The CVD risk factors were collected at baseline and at 6‐month follow‐up.

Results

Compared with lower ADA and AHEI‐2010 score participants, the higher score participants exhibited a significantly lower waist circumference, serum low‐density lipoprotein cholesterol level and 10‐year risk of CHD. Participants with higher ADA dietary scores had a significantly reduced risk of central obesity and systolic blood pressure >140 mmHg. Higher AHEI‐2010 scores were significantly related to a reduced risk of serum low‐density lipoprotein cholesterol > 100 mg dL‐1. Seven participants had their first‐ever CVD during the follow‐up period, although neither ADA score, nor AHEI‐2010 score could predict CVD incidence.

Conclusions

The ADA‐recommended dietary pattern and a higher AHEI‐2010 score might both exhibit reduced risk factors of CVD in T2DM patients.
Effects of high‐fidelity patient simulation led clinical reasoning course: Focused on nursing core competencies, problem solving, and academic self‐efficacy
Authors: Lee JuHee , Lee Yoonju , Lee Senah , Bae Juyeon
Published: May 2015

Aim

To examine the effects of high‐fidelity patient simulation (HFPS) led clinical reasoning course among undergraduate nursing students.

Methods

A quasi‐experimental study of non‐equivalent control group pretest–post test design was applied. A total of 49 senior nursing students participated in this study. The experimental group consisted of the students who took the “clinical reasoning” course (n = 23) while the control group consisted of students who did not (n = 26). Self‐administered scales including the nursing core competencies, problem solving, academic self‐efficacy, and Kolb learning style inventory were analyzed quantitatively using SPSS version 20.0. Data analysis was conducted using one‐way ancova due to a significant difference in nursing core competencies between the experimental group and control group.

Results

There was a significant improvement in nursing core competencies in the experimental group (F = 7.747, P = 0.008). The scores of problem solving and academic self‐efficacy were higher in the experimental group after the HFPS led clinical reasoning course without statistical difference.

Conclusion

There is a need for the development of effective instructional methods to improve learning outcomes in nursing education. Future research is needed related to simulation education as well as management strategies so that learning outcomes can be achieved within different students' learning style.