bluuebunny/crossref_metadata_2025_split huggingface dataset:
MRI‐negative temporal lobe epilepsy—What do we know?
Authors: Muhlhofer Wolfgang , Tan Yee‐Leng , Mueller Susanne G. , Knowlton Robert 
Published: March 2017

SummaryTemporal lobe epilepsy (TLE) is the most common focal epilepsy in adults. TLE has a high chance of becoming medically refractory, and as such, is frequently considered for further evaluation and surgical intervention. Up to 30% of TLE cases, however, can have normal (“nonlesional” or negative) magnetic resonance imaging (MRI) results, which complicates the presurgical workup and has been associated with worse surgical outcomes. Helped by contributions from advanced imaging techniques and electrical source localization, the number of surgeries performed on MRI‐negative TLE has increased over the last decade. Thereby new epidemiologic, clinical, electrophysiologic, neuropathologic, and surgical data of MRI‐negative TLE has emerged, showing characteristics that are distinct from those of lesional TLE. This review article summarizes what we know today about MRI‐negative TLE, and discusses the comprehensive assessment of patients with MRI‐negative TLE in a structured and systematic approach. It also includes a concise description of the most recent developments in structural and functional imaging, and highlights postprocessing imaging techniques that have been shown to add localization value in MRI‐negative epilepsies. We evaluate surgical outcomes of MRI‐negative TLE, identify prognostic makers of postoperative seizure freedom, and discuss strategies for optimizing the selection of surgical candidates in this group.
Signalling and targeted therapy of inflammatory cells in epidermolysis bullosa acquisita
Authors: Ludwig Ralf J. 
Published: March 2017

AbstractPemphigoid diseases (PDs) are chronic and life‐threatening autoimmune diseases of the skin and mucous membranes. PDs are characterized and caused by autoantibodies targeting components of the basement membrane. In the PD epidermolysis bullosa acquisita (EBA), the target autoantigen is type VII collagen. Current treatment options of PD, especially EBA, are limited and are mostly based on systemic immunosuppression. Animal models of PD have greatly advanced our understanding of PD pathogenesis. This has led to the identification of several novel therapeutic targets, including signalling molecules. Herein, the contribution of signalling molecules in the pathogenesis of the PD EBA and the effects of pharmacological targeting of these pathways are reviewed in detail. The p38 MAPK, ERK1/2, AKT, PI3Kβ, Hsp90, RORα, PDE4, Src kinases and CARD9 have been demonstrated to be critically involved in EBA pathogenesis. With the advent of new signal transduction inhibitors, we expect that the so far poor prognosis of EBA and other PD will improve significantly in the future.
The hair follicle enigma
Authors: Bernard Bruno A. 
Published: March 2017

AbstractThe hair follicle is a mini‐organ endowed with a unique structure and cyclic behaviour. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome‐mediated cell‐cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology.
Increased levels of circulating platelet‐derived microparticles are associated with metastatic cutaneous melanoma
Authors: Moreau Joséphine , Pelletier Fabien , Biichle Sabeha , Mourey Guillaume , Puyraveau Marc , Badet Nicolas , Caubet Matthieu , Laresche Claire , Garnache‐Ottou Francine , Saas Philippe , Seilles Estelle , Aubin François 
Published: March 2017

AbstractWe investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL−1) than in patients with stage III (2041 μL−1) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut‐off value (5311 μL−1) allowing the distinction between high‐risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma.
Analysis of the skin of mice humanized for the immune system
Authors: Centlivre Mireille , Petit Maxime , Hutton Andrew J. , Dufossée Mélody , Boccara David , Mimoun Maurice , Soria Angèle , Combadière Béhazine 
Published: March 2017

AbstractDevelopment of new immunotherapeutic strategies relies on the ability to activate the right cells at the right place and at the right moment and on the capacity of these cells to home to the right organ(s). Skin delivery has shown high potency for immunotherapeutic administration. However, an adequate in vivo model of human skin immunity is still a critical bottleneck. We demonstrated here that the skin of human immune system mice is colonized by human hematopoietic cells, mainly human T cells and that complementation with human antigen‐presenting cells at the vaccination site allowed the induction of an immune response.
Effect of bucladesine, pentoxifylline, and H‐89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain
Authors: Salehi Forouz , Hosseini‐Zare Mahshid S. , Aghajani Haleh , Seyedi Seyedeh Yalda , Hosseini‐Zare Maryam S. , Sharifzadeh Mohammad 
Published: March 2017

AbstractThe aim of this study was to determine the effects of cyclic adenosine monophosphate (cAMP) and its dependent pathway on thermal nociception in a mouse model of acute pain. Here, we studied the effect of H‐89 (protein kinase A inhibitor), bucladesine (Db‐cAMP) (membrane‐permeable analog of cAMP), and pentoxifylline (PTX; nonspecific phosphodiesterase (PDE) inhibitor) on pain sensation. Different doses of H‐89 (0.05, 0.1, and 0.5 mg/100 g), PTX (5, 10, and 20 mg/100 g), and Db‐cAMP (50, 100, and 300 nm/mouse) were administered intraperitoneally (I.p.) 15 min before a tail‐flick test. In combination groups, we injected the first and the second compounds 30 and 15 min before the tail‐flick test, respectively. I.p. administration of H‐89 and PTX significantly decreased the thermal‐induced pain sensation in their low applied doses. Db‐cAMP, however, decreased the pain sensation in a dose‐dependent manner. The highest applied dose of H‐89 (0.5 mg/100 g) attenuated the antinociceptive effect of Db‐cAMP in doses of 50 and 100 nm/mouse. Surprisingly, Db‐cAMP decreased the antinociceptive effect of the lowest dose of H‐89 (0.05 mg/100 g). All applied doses of PTX reduced the effect of 0.05 mg/100 g H‐89 on pain sensation; however, the highest dose of H‐89 compromised the antinociceptive effect of 20 mg/100 g dose of PTX. Co‐administration of Db‐cAMP and PTX increased the antinociceptive effect of each compound on thermal‐induced pain. In conclusion, PTX, H‐89, and Db‐cAMP affect the thermal‐induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide‐dependent protein kinases.
Arctic shrub growth trajectories differ across soil moisture levels
Authors: Ackerman Daniel , Griffin Daniel , Hobbie Sarah E. , Finlay Jacques C. 
Published: March 2017

AbstractThe circumpolar expansion of woody deciduous shrubs in arctic tundra alters key ecosystem properties including carbon balance and hydrology. However, landscape‐scale patterns and drivers of shrub expansion remain poorly understood, inhibiting accurate incorporation of shrub effects into climate models. Here, we use dendroecology to elucidate the role of soil moisture in modifying the relationship between climate and growth for a dominant deciduous shrub, Salix pulchra, on the North Slope of Alaska, USA. We improve upon previous modeling approaches by using ecological theory to guide model selection for the relationship between climate and shrub growth. Finally, we present novel dendroecology‐based estimates of shrub biomass change under a future climate regime, made possible by recently developed shrub allometry models. We find that S. pulchra growth has responded positively to mean June temperature over the past 2.5 decades at both a dry upland tundra site and an adjacent mesic riparian site. For the upland site, including a negative second‐order term in the climate–growth model significantly improved explanatory power, matching theoretical predictions of diminishing growth returns to increasing temperature. A first‐order linear model fit best at the riparian site, indicating consistent growth increases in response to sustained warming, possibly due to lack of temperature‐induced moisture limitation in mesic habitats. These contrasting results indicate that S. pulchra in mesic habitats may respond positively to a wider range of temperature increase than S. pulchra in dry habitats. Lastly, we estimate that a 2°C increase in current mean June temperature will yield a 19% increase in aboveground S. pulchra biomass at the upland site and a 36% increase at the riparian site. Our method of biomass estimation provides an important link toward incorporating dendroecology data into coupled vegetation and climate models.
Counting invasive breast cancer cells in the HER2 silver in‐situ hybridization test: how many cells are enough?
Authors: Polónia António , Eloy Catarina , Pinto João , Braga Ana Costa , Oliveira Guilherme , Schmitt Fernando 
Published: March 2017

AimTo evaluate the intraobserver and interobserver reproducibility of the HER2 in‐situ hybridization (ISH) test in breast cancer by measuring the impact of counting different numbers of invasive cancer cells.Methods and resultsA cohort of 101 primary invasive breast cancer cases were evaluated for HER2 gene amplification by silver ISH, and the concordance among four observers with different levels of experience, counting different numbers of invasive cancer cells, was determined. The evaluation of the samples included scoring 20 nuclei, in three different areas. The cases were scored twice, with a washout interval of at least 2 weeks. We observed an increase in the intraobserver concordance rate between the first and second evaluations with an increase in cell count. A count of 60 invasive cells was needed to obtain a concordance rate near 95% and an agreement rate greater than 0.80 by all observers. The interobserver concordance rate of the HER2 test also increased with the increase in cell count, reaching at least a 90% concordance rate with a count of 60 invasive cells. The median variability of both the HER2/CEP17 ratio and the average HER2 copy number between different evaluations decreased with the increase in cell count, being statistically higher in HER2‐positive cases.ConclusionsThe minimal cell number recommended in current guidelines should be raised to at least 40, and preferably 60, invasive cells. Moreover, cases with amplification levels close to the threshold should be subjected to a dual count from an experienced observer.
Skin delivery of hydrophilic molecules from liposomes and polysaccharide‐coated liposomes
Authors: Belhaj N. , Arab‐Tehrany E. , Loing E. , Bézivin C. 
Published: March 2017

AbstractObjectivesLiposomes are commonly used in cosmetic formulations to increase the bioavailability of active ingredients. We have previously shown that polysaccharide coating of liposomes improves their resistance to surfactants and electrolytes. In the current study, we have assessed the impact of coating on the skin penetration enhancer properties of liposomes.MethodsThe physicochemical properties of coated liposomes (Ionosomes™) were evaluated before and after encapsulation of two different hydrophilic molecules (caffeine and a hexapeptide), and compared to those observed with non‐coated liposomes. Moreover, in vitro permeation experiments were performed using Franz™‐modified diffusion cells, with normal human skin as membranes.ResultsResults showed that both coated and non‐coated liposomes significantly improved the bioavailability of hydrophilic active molecules in skin, compared to reference solutions. Although liposome coating slightly reduced entrapment efficiency, the delivery of active molecules was not adversely affected by the process. In conclusion, polysaccharide coating of liposomes allows for better protection of their integrity without compromising the skin bioavailability of the active molecules that they convoy.
IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population
Authors: Queiroz G. A. , Costa R. S. , Alcantara‐Neves N. M. , Nunes de Oliveira Costa G. , Barreto M. L. , Carneiro V. L. , Figueiredo C. A. 
Published: March 2017

SummaryAtopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin‐4 (IL‐4), interleukin‐5 (IL‐5) and interleukin‐13 (IL‐13). Interleukin‐33 (IL‐33) appears to be a potent inducer of Th2 immune response. This occurs when IL‐33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL‐5 and IL‐13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53–0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL‐5 production (OR 1.36, 95% CI: 1.09–1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07–1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08–2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.
Effectiveness of a polyhexanide irrigation solution on methicillin‐resistant Staphylococcus aureus biofilms in a porcine wound model
Authors: Davis Stephen C , Harding Andrew , Gil Joel , Parajon Fernando , Valdes Jose , Solis Michael , Higa Alex 
Published: March 2017

AbstractIrrigation and removal of necrotic debris can be beneficial for proper healing. It is becoming increasingly evident that wounds colonized with biofilm forming bacteria, such as Staphylococcus aureus (SA), can be more difficult to eradicate. Here we report our findings of the effects of an irrigation solution containing propyl‐betaine and polyhexanide (PHMB) on methicillin‐resistant Staphylococcus aureus (MRSA) biofilms in a porcine wound model. Thirty‐nine deep partial thickness wounds were created with six wounds assigned to one of six treatment groups: (i) PHMB, (ii) Ringer's solution, (iii) hypochlorous acid/sodium hypochlorite, (iv) sterile water, (v) octenidine dihydrochloride, and (vi) octenilin. Wounds were inoculated with MRSA and covered with a polyurethane dressing for 24 hours to allow biofilm formation. The dressings were then removed and the wounds were irrigated twice daily for 3 days with the appropriate solution. MRSA from four wounds were recovered from each treatment group at 3 days and 6 days hours after initial treatment. Irrigation of wounds with the PHMB solution resulted in 97·85% and 99·64% reductions of MRSA at the respective 3 days and 6 days assessment times when compared to the untreated group. Both of these reductions were statistically significant compared to all other treatment groups (P values <0·05).
Low‐temperature preparation of titanium diboride fine powder via magnesiothermic reduction in molten salt
Authors: Bao Ke , Wen Yan , Khangkhamano Matthana , Zhang Shaowei 
Published: March 2017

AbstractPhase pure titanium diboride (TiB2) powder of 100‐200 nm was synthesized from TiO2 and B2O3 using a molten‐salt‐assisted magnesiothermic reduction technique. The effects of salt type, Mg amount, reaction temperature, and TiO2 raw materials on the synthesis process were examined and the relevant reaction mechanisms discussed. Among the three chloride salts (NaCl, KCl, and MgCl2), MgCl2 showed the best accelerating‐effect. To synthesize phase pure TiB2, 20 mol% excessive Mg had to be used to compensate for the evaporation loss of Mg. Particle shape and size of raw material TiO2 showed little effect on the formation of TiB2 and its shape and size, suggesting that relatively cheaper and coarser TiO2 raw materials could be used for low‐temperature synthesis of TiB2 fine particles. The “dissolution‐precipitation” mechanism governed the overall molten salt synthesis process.
Mitochondrial PKC‐ε deficiency promotes I/R‐mediated myocardial injury via GSK3β‐dependent mitochondrial permeability transition pore opening
Authors: Wang Shijun , Zhang Feng , Zhao Gang , Cheng Yong , Wu Ting , Wu Bing , Zhang You‐en 
Published: March 2017

AbstractMitochondrial fission is critically involved in cardiomyocyte apoptosis, which has been considered as one of the leading causes of ischaemia/reperfusion (I/R)‐induced myocardial injury. In our previous works, we demonstrate that aldehyde dehydrogenase‐2 (ALDH2) deficiency aggravates cardiomyocyte apoptosis and cardiac dysfunction. The aim of this study was to elucidate whether ALDH2 deficiency promotes mitochondrial injury and cardiomyocyte death in response to I/R stress and the underlying mechanism. I/R injury was induced by aortic cross‐clamping for 45 min. followed by unclamping for 24 hrs in ALDH2 knockout (ALDH2−/−) and wild‐type (WT) mice. Then myocardial infarct size, cell apoptosis and cardiac function were examined. The protein kinase C (PKC) isoform expressions and their mitochondrial translocation, the activity of dynamin‐related protein 1 (Drp1), caspase9 and caspase3 were determined by Western blot. The effects of N‐acetylcysteine (NAC) or PKC‐δ shRNA treatment on glycogen synthase kinase‐3β (GSK‐3β) activity and mitochondrial permeability transition pore (mPTP) opening were also detected. The results showed that ALDH2−/− mice exhibited increased myocardial infarct size and cardiomyocyte apoptosis, enhanced levels of cleaved caspase9, caspase3 and phosphorylated Drp1. Mitochondrial PKC‐ε translocation was lower in ALDH2−/− mice than in WT mice, and PKC‐δ was the opposite. Further data showed that mitochondrial PKC isoform ratio was regulated by cellular reactive oxygen species (ROS) level, which could be reversed by NAC pre‐treatment under I/R injury. In addition, PKC‐ε inhibition caused activation of caspase9, caspase3 and Drp1Ser616 in response to I/R stress. Importantly, expression of phosphorylated GSK‐3β (inactive form) was lower in ALDH2−/− mice than in WT mice, and both were increased by NAC pre‐treatment. I/R‐induced mitochondrial translocation of GSK‐3β was inhibited by PKC‐δ shRNA or NAC pre‐treatment. In addition, mitochondrial membrane potential (∆Ψm) was reduced in ALDH2−/− mice after I/R, which was partly reversed by the GSK‐3β inhibitor (SB216763) or PKC‐δ shRNA. Collectively, our data provide the evidence that abnormal PKC‐ε/PKC‐δ ratio promotes the activation of Drp1 signalling, caspase cascades and GSK‐3β‐dependent mPTP opening, which results in mitochondrial injury‐triggered cardiomyocyte apoptosis and myocardial dysfuction in ALDH2−/− mice following I/R stress.
Histone deacetylase inhibitors promote eNOS expression in vascular smooth muscle cells and suppress hypoxia‐induced cell growth
Authors: Tan Xiaoling , Feng Lan , Huang Xiaoyong , Yang Yidong , Yang Chengzhong , Gao Yuqi 
Published: March 2017

AbstractHypoxia stimulates excessive growth of vascular smooth muscle cells (VSMCs) contributing to vascular remodelling. Recent studies have shown that histone deacetylase inhibitors (HDIs) suppress VSMC proliferation and activate eNOS expression. However, the effects of HDI on hypoxia‐induced VSMC growth and the role of activated eNOS in VSMCs are unclear. Using an EdU incorporation assay and flow cytometry analysis, we found that the HDIs, butyrate (Bur) and suberoylanilide hydroxamic acid (SAHA) significantly suppressed the proliferation of hypoxic VSMC lines and induced apoptosis. Remarkable induction of cleaved caspase 3, p21 expression and reduction of PCNA expression were also observed. Increased eNOS expression and enhanced NO secretion by hypoxic VSMC lines were detected using Bur or SAHA treatment. Knockdown of eNOS by siRNA transfection or exposure of hypoxic VSMCs to NO scavengers weakened the effects of Bur and SAHA on the growth of hypoxic VSMCs. In animal experiments, administration of Bur to Wistar rats exposed to hypobaric hypoxia for 28 days ameliorated the thickness and collagen deposition in pulmonary artery walls. Although the mean pulmonary arterial pressure (mPAP) was not obviously decreased with Bur in hypoxic rats, right ventricle hypertrophy index (RVHI) was decreased and the oxygen partial pressure of arterial blood was elevated. Furthermore, cell viability was decreased and eNOS and cleaved caspase 3 were induced in HDI‐treated rat pulmonary arterial SMCs. These findings imply that HDIs prevent hypoxia‐induced VSMC growth, in correlation with activated eNOS expression and activity in hypoxic VSMCs.
Nutrition, dental caries and periodontal disease: a narrative review
Authors: Hujoel Philippe P. , Lingström Peter 
Published: March 2017

AbstractAimTo provide a narrative review of the role of macro‐ and micronutrients in relation to dental caries, gingival bleeding and destructive periodontal disease.Materials & MethodsThis review is based on systematic reviews (when available) and comparative human studies.ResultsDental caries cannot develop without the presence of dietary fermentable carbohydrates, in particular sugar. The susceptibility to develop caries in the presence of carbohydrates may be influenced by genetics and micronutrients such as vitamin D. Gingival bleeding and destructive periodontal disease are sensitive markers to both abnormalities in macronutrient content (excessive carbohydrates or poly‐unsaturated fat intake, deficient protein intake) and micronutrient intake (e.g. vitamin C and B12).ConclusionDental caries and periodontal diseases are a sensitive alarm bell for an unhealthy diet, which predicts the future onset of the diseases of civilizations.