bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation-Induced Mucosal KYNU Expression Identifies Human Ileal Crohn’s Disease
Authors: Huhn Meik , Herrero San Juan Martina , Melcher Balint , Dreis Caroline , Schmidt Katrin G. , Schwiebs Anja , Collins Janet , Pfeilschifter Josef M. , Vieth Michael , Stein Jürgen , Radeke Heinfried H.
Published: May 2020

The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise questions regarding the unclarified heterogeneity of pathological mechanisms promoting disease progression. While biomarkers for the differentiation of Crohn’s disease (CD) versus ulcerative colitis (UC) have been suggested, specific markers for a CD subclassification in ileal CD versus colonic CD are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterize potential biomarkers by focusing on the downstream enzymes and metabolites of kynurenine metabolism. Using immunohistochemical stainings, we analyzed and compared the mucosal tryptophan immune metabolism in bioptic samples from patients with active inflammation due to UC or CD versus healthy controls. Localization-specific quantification of immune cell infiltration, tryptophan-metabolizing enzyme expression and mucosal tryptophan downstream metabolite levels was performed. We found generally increased immune cell infiltrates in the tissue of all patients with IBD. However, in patients with CD, significant differences were found between regulatory T cell and neutrophil granulocyte infiltration in the ileum compared with the colon. Furthermore, we observed decreased kynurenine levels as well as strong kynureninase (KYNU) expression specifically in patients with ileal CD. Correspondingly, significantly elevated levels of the kynurenine metabolite 3-hydroxyanthranilic acid were detected in the ileal CD samples. Highlighting the heterogeneity of the different phenotypes of CD, we identified KYNU as a potential mucosal biomarker allowing the localization-specific differentiation of ileal CD versus colonic CD.
Intrahepatic Cholestasis in Pregnancy: Review of the Literature
Authors: Piechota Joanna , Jelski Wojciech
Published: May 2020

Intrahepatic cholestasis of pregnancy (ICP) is the most common hepatic disorder related to pregnancy in women. It usually develops within the third trimester of pregnancy and presents with pruritus as well as elevated levels of bile acid and/or alanine aminotransferase. Clinical signs quickly resolve after delivery; however, there is a high risk of the disorder recurring in subsequent pregnancies. ICP is associated with an increased risk of perinatal complications (premature birth, respiratory disorders, even stillbirth). Elevated levels of gestational hormones and genetic predispositions are important factors for the development of ICP; among the latter, mutations in hepatobiliary transport proteins (multidrug resistance protein 3-MDR3, bile salt export pump- BSEP) play a major role. Clinical and biochemical symptoms of ICP include pruritus and increased levels of total bile acids (TBA). Serum levels of TBA should be monitored in ICP patients throughout the pregnancy as concentrations above 40 μmol/L, which define that severe ICP isassociated with an increased risk of fetal complications. Therapeutic management is aimed at reducing the clinical symptoms, normalizing maternal biochemistry and preventing complications to the fetus. Pharmacological treatment of intrahepatic cholestasis of pregnancy consists of the administration of ursodeoxycholic acid to lower the levels of TBA and possibly reduce pruritus. If the treatment fails, premature delivery should be considered.
Immune Checkpoint Inhibitors for Lung Cancer Treatment: A Review
Authors: Onoi Keisuke , Chihara Yusuke , Uchino Junji , Shimamoto Takayuki , Morimoto Yoshie , Iwasaku Masahiro , Kaneko Yoshiko , Yamada Tadaaki , Takayama Koichi
Published: May 2020

The treatment of lung cancer has changed drastically in recent years owing to the advent of immune checkpoint inhibitors (ICIs). A 1992 study reported that programmed cell death-1 (PD-1), an immune checkpoint molecule, is upregulated during the induction of T cell death. Since then, various immunoregulatory mechanisms involving PD-1 have been clarified, and the successful use of PD-1 blockers in anticancer therapy eventually led to the development of the current generation of ICIs. Nivolumab was the first ICI approved for treating lung cancer in 2014. Since then, various ICIs such as pembrolizumab, atezolizumab, and durvalumab have been successively introduced into clinical medicine and have shown remarkable efficacy. The introduction of ICIs constituted a major advancement in lung cancer treatment, but disease prognosis continues to remain low. Therefore, new molecular-targeted therapies coupled with existing anticancer drugs and radiotherapy have recently been explored. This review encompasses the current status, challenges, and future perspectives of ICI treatment in lung cancer.
Serotonin-Secreting Neuroendocrine Tumours of the Pancreas
Authors: Milanetto Anna Caterina , Fassan Matteo , David Alina , Pasquali Claudio
Published: May 2020

Background: Serotonin-secreting pancreatic neuroendocrine tumours (5-HT-secreting pNETs) are very rare, and characterised by high urinary 5-hydroxyindole-acetic acid (5-HIAA) levels (or high serum 5-HT levels). Methods: Patients with 5-HT-secreting pancreatic neoplasms observed in our unit (1986–2015) were included. Diagnosis was based on urinary 5-HIAA or serum 5-HT levels. Results: Seven patients were enrolled (4 M/3 F), with a median age of 64 (range 38–69) years. Two patients had a carcinoid syndrome. Serum 5-HT was elevated in four patients. Urinary 5-HIAA levels were positive in six patients. The median tumour size was 4.0 (range 2.5–10) cm. All patients showed liver metastases at diagnosis. None underwent resective surgery; lymph node/liver biopsies were taken. Six lesions were well-differentiated tumours and one a poorly differentiated carcinoma (Ki67 range 3.4–70%). All but one patient received chemotherapy. Four patients received somatostatin analogues; three patients underwent ablation of liver metastases. One patient is alive with disease 117 months after observation. All the others died from disease progression after a follow-up within 158 months. Conclusions: Primary 5-HT-secreting pNETs are mostly metastatic to the liver; patients are not amenable to resective surgery. Despite high 5-HIAA urinary levels, few patients present with carcinoid syndrome. A five-year survival rate of 42.9% may be achieved with multimodal treatment.
ECG Indices Poorly Predict Left Ventricular Hypertrophy and Are Applicable Only in Individuals with Low Cardiovascular Risk
Authors: Chlabicz Małgorzata , Jamiołkowski Jacek , Paniczko Marlena , Sowa Paweł , Szpakowicz Małgorzata , Łapińska Magda , Jurczuk Natalia , Kondraciuk Marcin , Ptaszyńska-Kopczyńska Katarzyna , Raczkowski Andrzej , Szpakowicz Anna , Kamiński Karol Adam
Published: May 2020

Background: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular events. The electrocardiography (ECG) has poor sensitivity, but it is commonly used to detect LVH. Aim: To evaluate the diagnostic efficacy of known ECG indicators to recognize LVH in subgroups with different cardiovascular risk levels. Methods: 676 volunteers were included. Results: We found that 10.2% of the analyzed population had LVH based on echocardiography. Individuals with LVH were older, had a higher body mass index, higher systolic blood pressure, lower heart rate, higher parameters of insulin resistance, higher cardiovascular risk, and android-type obesity. Variables that remained independently associated with LVH were QRS duration, left atrial volume index, troponin T, and hemoglobin A1c. The receiver operating characteristics (ROC) curve analysis of the Sokolow–Lyon index did not show a significant predictive ability to diagnose LVH in the whole study population including all cardiovascular risk classes. The ROC curves analysis of Cornell and Lewis indices showed a modest predictive ability to diagnose LVH in the general population and in a low cardiovascular class. Conclusions: There is a need for new, simple methods to diagnose LVH in the general population in order to properly evaluate cardiovascular risk and introduce optimal medical treatment of concomitant disease.
Psychosocial Impact of Predictive Genetic Testing in Hereditary Heart Diseases: The PREDICT Study
Authors: Bordet Céline , Brice Sandrine , Maupain Carole , Gandjbakhch Estelle , Isidor Bertrand , Palmyre Aurélien , Moerman Alexandre , Toutain Annick , Akloul Linda , Brehin Anne-Claire , Sawka Caroline , Rooryck Caroline , Schaefer Elise , Nguyen Karine , Dupin Deguine Delphine , Rouzier Cécile , Billy Gipsy , Séné Krystelle , Denjoy Isabelle , Leheup Bruno , Planes Marc , Mazzella Jean-Michael , Staraci Stéphanie , Hebert Mélanie , Le Boette Elsa , Michon Claire-Cécile , Babonneau Marie-Lise , Curjol Angélique , Bekhechi Amine , Mansouri Rafik , Raji Ibticem , Pruny Jean-François , Fressart Véronique , Ader Flavie , Richard Pascale , Tezenas du Montcel Sophie , Gargiulo Marcela , Charron Philippe
Published: May 2020

Predictive genetic testing (PGT) is offered to asymptomatic relatives at risk of hereditary heart disease, but the impact of result disclosure has been little studied. We evaluated the psychosocial impacts of PGT in hereditary heart disease, using self-report questionnaires (including the State-Trait Anxiety Inventory) in 517 adults, administered three times to the prospective cohort (PCo: n = 264) and once to the retrospective cohort (RCo: n = 253). The main motivations for undergoing PGT were “to remove doubt” and “for their children”. The level of anxiety increased between pre-test and result appointments (p <0.0001), returned to baseline after the result (PCo), and was moderately elevated at 4.4 years (RCo). Subjects with a history of depression or with high baseline anxiety were more likely to develop anxiety after PGT result (p = 0.004 and p <0.0001, respectively), whatever it was. Unfavourable changes in professional and/or family life were observed in 12.4% (PCo) and 18.7% (RCo) of subjects. Few regrets about PGT were expressed (0.8% RCo, 2.3% PCo). Medical benefit was not the main motivation, which emphasises the role of pre/post-test counselling. When PGT was performed by expert teams, the negative impact was modest, but careful management is required in specific categories of subjects, whatever the genetic test result.
Adenosine and the Cardiovascular System: The Good and the Bad
Authors: Guieu Régis , Deharo Jean-Claude , Maille Baptiste , Crotti Lia , Torresani Ermino , Brignole Michele , Parati Gianfranco
Published: May 2020

Adenosine is a nucleoside that impacts the cardiovascular system via the activation of its membrane receptors, named A1R, A2AR, A2BR and A3R. Adenosine is released during hypoxia, ischemia, beta-adrenergic stimulation or inflammation and impacts heart rhythm and produces strong vasodilation in the systemic, coronary or pulmonary vascular system. This review summarizes the main role of adenosine on the cardiovascular system in several diseases and conditions. Adenosine release participates directly in the pathophysiology of atrial fibrillation and neurohumoral syncope. Adenosine has a key role in the adaptive response in pulmonary hypertension and heart failure, with the most relevant effects being slowing of heart rhythm, coronary vasodilation and decreasing blood pressure. In other conditions, such as altitude or apnea-induced hypoxia, obstructive sleep apnea, or systemic hypertension, the adenosinergic system activation appears in a context of an adaptive response. Due to its short half-life, adenosine allows very rapid adaptation of the cardiovascular system. Finally, the effects of adenosine on the cardiovascular system are sometimes beneficial and other times harmful. Future research should aim to develop modulating agents of adenosine receptors to slow down or conversely amplify the adenosinergic response according to the occurrence of different pathologic conditions.
A U-Shaped Relationship between the Prevalence of Frailty and Body Mass Index in Community-Dwelling Japanese Older Adults: The Kyoto–Kameoka Study
Authors: Watanabe Daiki , Yoshida Tsukasa , Watanabe Yuya , Yamada Yosuke , Kimura Misaka
Published: May 2020

The relationship between body mass index (BMI) and frailty remains unclear. Using two validated frailty assessment tools, this study aimed to investigate the relationship between the prevalence of frailty and BMI in Japanese older adults. This cross-sectional study used baseline data of 7191 individuals aged ≥65 years, living in Kameoka City, Kyoto, Japan. The BMI was calculated based on self-reported height and body weight, and classified into six categories. Frailty was defined using two validated assessment tools, the Fried phenotype (FP) model and Kihon Checklist (KCL). We evaluated the relationship between frailty and BMI using a multivariate restricted cubic spline logistic regression. The prevalence of frailty defined using the FP model was 25.3%, 19.6%, 14.3%, 12.4%, 12.6%, and 19.4% for each BMI category of <18.5, 18.5–19.9, 20.0–22.4, 22.5–24.9, 25.0–27.4, and ≥27.5 kg/m2, respectively. The spline model showed a significant U-shaped relationship between BMI and the prevalence of frailty defined using both, KCL and FP models. This study found that the BMI range corresponding to lowest prevalence of frailty defined using both tools was 21.4–25.7 kg/m2. Thus, a healthy BMI may reduce the prevalence of frailty, and the risk of frailty needs to be evaluated in individuals who are underweight or overweight.
Association between Anxiety and Vascular Dementia Risk: New Evidence and an Updated Meta-Analysis
Authors: Santabárbara Javier , Lipnicki Darren M. , Olaya Beatriz , Villagrasa Beatriz , Gracia-García Patricia , Bueno-Notivol Juan , Lobo Antonio , López-Antón Raúl
Published: May 2020

The association between anxiety and vascular dementia (VaD) is unclear. We aimed to reliably estimate the association between anxiety and VaD risk using meta-analysis to pool new results from a large community-based cohort (Zaragoza Dementia and Depression (ZARADEMP) study) and results from previous studies. ZARADEMP participants (n = 4057) free of dementia were followed up on for up to 12 years. Cases and subcases of anxiety were determined at baseline. A panel of four psychiatrists diagnosed incident cases of VaD by consensus. We searched for similar studies published up to October 2019 using PubMed and Web of Science. Observational studies reporting associations between anxiety and VaD risk, and adjusting at least for age, were selected. Odds ratios (ORs) from each study were combined using fixed-effects models. In the ZARADEMP study, the risk of VaD was 1.41 times higher among individuals with anxiety (95% CI: 0.75–2.68) compared with non-cases (p = 0.288). Pooling this result with results from two previous studies yielded an OR of 1.65 (95% CI: 1.07–2.53; p = 0.022). These findings indicate that anxiety is associated with an increased risk of VaD. Taking into account that anxiety is commonly observed in the elderly, treating and preventing it might reduce the prevalence and incidence of VaD. However, whether anxiety is a cause of a prodrome of VaD is still unknown, and future research is needed to clarify this.
D-Chiro-Inositol Improves Sperm Mitochondrial Membrane Potential: In Vitro Evidence
Authors: Condorelli Rosita A. , Barbagallo Federica , Calogero Aldo E. , Cannarella Rossella , Crafa Andrea , La Vignera Sandro
Published: May 2020

The use of inositols in endocrinological clinical practice is increasingly widespread. Most of the existing evidence concerns myoinositol (MYO), the most abundant form in nature, especially in women with polycystic ovarian syndrome. We have previously shown that MYO increases sperm motility in patients with asthenozoospermia by the increase of sperm mitochondrial membrane potential (MMP), a biofunctional sperm parameter closely associated to sperm motility. The aim of this study was to evaluate the effects of D-chiro-inositol (DCI), another biologically active isoform of inositols, on sperm MMP, as data on this matter has never been released so far. To accomplish this, semen samples from 15 patients with asthenozoospermia and 15 healthy normozoospermic men were incubated with increasing concentrations of DCI (0, 75, and 750 µg/mL) or phosphate buffer saline for 30 min. Incubation with DCI significantly improved sperm MMP at lower concentrations, and with shorter incubation length than those used in our similar MYO studies. In conclusion, these findings indicate that DCI positively impacts on sperm mitochondrial function in vitro. Studies aimed at assessing the role of DCI in the treatment of asthenozoospermia in-vivo are warranted.
Leakage and Stenosis of the Hepaticojejunostomy Following Surgery for Perihilar Cholangiocarcinoma
Authors: Bednarsch Jan , Czigany Zoltan , Heise Daniel , Lang Sven Arke , Olde Damink Steven W. M. , Luedde Tom , Bruners Philipp , Ulmer Tom Florian , Neumann Ulf Peter
Published: May 2020

This study aims to provide a deep insight into the incidence and clinical significance of postoperative anastomotic leakage (AL) and anastomotic stenosis (AS) of the hepaticojejunostomy (HJ) after curative-intent liver resection for perihilar cholangiocarcinoma (pCCA). Between 2011 and mid-2019, 114 patients with pCCA underwent surgery in curative intent at our institution and were analyzed regarding the postoperative incidence of AL and AS. Further, associations between AL and AS and clinical characteristics were assessed using multiple univariate logistic regression analyses. AL was diagnosed in 11.4% (13/114) of the patients resulting in postoperative mortality in the minority of patients (23.0%, 3/13). AS occurred in 11.0% (11/100) of the individuals eligible for follow-up with local tumor recurrence being the underlying pathology in 72.7% (8/11) of the cases. None of the investigated clinical factors including surgical difficulty of the HJ showed a meaningful association with AL or AS. AL and AS are frequent complications and can be treated by conservative, interventional or surgical therapy with a high success rate. Also, technical difficulty of the HJ appears not to be not associated with the occurrence of AL or AS. Moreover, AS is associated with tumor recurrence in the majority of cases.
Evaluation of Urban Landscape Outdoor Advertisement Signboards Using Virtual Reality
Authors: Lee Young-Woo , Huh Jun-Ho
Published: May 2020

The social interest in outdoor advertising signs, which have been recognized as an important element affecting impressions of a town, has been gradually increasing. However, when these signs are fully scattered around commercial areas, an oppressive feeling may be experienced by people, which cannot be neglected. Thus, this paper attempts to identify the characteristics of such visual oppression in urban landscapes through factor analysis, aiming to control them in such a way that does not oppress people. In addition, comparisons between Japanese and foreign nationals (i.e., foreign students from the Republic of Korea and the People’s Republic of China) were carried out, in order to check for any differences in perception of oppressive feelings depending on nationality. At the same time, to check for the possibility of different levels of perception depending on nationality, 20 Japanese and 20 foreign nationals (including Koreans and Chinese) were selected as test subjects. We expect this study to provide useful research material when reviewing the possibility of creating desirable urban landscapes or establishing guidelines for outdoor advertisements. For the research, landscape pictures focusing on outdoor advertising signs (15 wall, 6 roof-top, and 6 projection advertising signs) were taken as a sample for analysis. They were then presented in a 3D cyberdome for factor analysis, focusing on an impression evaluation test in relation to oppressive feelings. In addition, among the data obtained from the sample analysis, “Proportion,” which was considered to be the most influential factor on the oppressive feeling, was studied. The correlation coefficient between these two populations was 0.918, revealing a high level of correlation; thus, all subjects were treated as a single population. The factor analysis revealed 50.87% for the first factor (Evaluation), 25.39% for the second factor (capacity), and 9.47% for the third factor (Emotion), suggesting a relationship wherein the first factor decreased when the oppressive feeling increased; while the oppressive feeling increased along with the second factor.
Hydrogen vs. Halogen Bonds in 1-Halo-Closo-Carboranes
Authors: Alkorta Ibon , Elguero Jose , Oliva-Enrich Josep M.
Published: May 2020

A theoretical study of the hydrogen bond (HB) and halogen bond (XB) complexes between 1-halo-closo-carboranes and hydrogen cyanide (NCH) as HB and XB probe has been carried out at the MP2 computational level. The energy results show that the HB complexes are more stable than the XBs for the same system, with the exception of the isoenergetic iodine derivatives. The analysis of the electron density with the quantum theory of atoms in molecules (QTAIM) shows the presence of a unique intermolecular bond critical point with the typical features of weak noncovalent interactions (small values of the electron density and positive Laplacian and total energy density). The natural energy decomposition analysis (NEDA) of the complexes shows that the HB and XB complexes are dominated by the charge-transfer and polarization terms, respectively. The work has been complemented with a search in the CSD database of analogous complexes and the comparison of the results, with those of the 1-halobenzene:NCH complexes showing smaller binding energies and larger intermolecular distances as compared to the 1-halo-closo-carboranes:NCH complexes.
Healable Carbon Fiber-Reinforced Epoxy/Cyclic Olefin Copolymer Composites
Authors: Mahmood Haroon , Dorigato Andrea , Pegoretti Alessandro
Published: May 2020

Cyclic olefin copolymer (COC) particles were dispersed in various amounts in an epoxy matrix, and the resulting blends were used to impregnate unidirectional carbon fibers (CF) by hand lay-up. The thermal stability was not substantially modified by the presence of COC particles. The mixture of the two polymers resulted in a phase separated blend and the flexural modulus and interlaminar shear strength progressively decreased with the addition of COC particles in the laminates. Mode I fracture toughness tests were executed on double cantilever beam specimens. The opened crack was then thermally mended at 190 °C for 1 h. The laminates containing 30 wt.% of COC particles showed a healing efficiency of ~180%.
Rare Neurologic Disease-Associated Mutations of AIMP1 Are Related with Inhibitory Neuronal Differentiation Which Is Reversed by Ibuprofen
Authors: Takeuchi Yu , Tanaka Marina , Okura Nanako , Fukui Yasuyuki , Noguchi Ko , Hayashi Yoshihiro , Torii Tomohiro , Ooizumi Hiroaki , Ohbuchi Katsuya , Mizoguchi Kazushige , Miyamoto Yuki , Yamauchi Junji
Published: May 2020

Background: Hypomyelinating leukodystrophy 3 (HLD3), previously characterized as a congenital diseases associated with oligodendrocyte myelination, is increasingly regarded as primarily affecting neuronal cells. Methods: We used N1E-115 cells as the neuronal cell model to investigate whether HLD3-associated mutant proteins of cytoplasmic aminoacyl-tRNA synthase complex-interacting multifunctional protein 1 (AIMP1) aggregate in organelles and affect neuronal differentiation. Results: 292CA frame-shift type mutant proteins harboring a two-base (CA) deletion at the 292th nucleotide are mainly localized in the lysosome where they form aggregates. Similar results are observed in mutant proteins harboring the Gln39-to-Ter (Q39X) mutation. Interestingly, the frame-shift mutant-specific peptide specifically interacts with actin to block actin fiber formation. The presence of actin with 292CA mutant proteins, but not with wild type or Q39X ones, in the lysosome is detectable by immunoprecipitation of the lysosome. Furthermore, expression of 292CA or Q39X mutants in cells inhibits neuronal differentiation. Treatment with ibuprofen reverses mutant-mediated inhibitory differentiation as well as the localization in the lysosome. Conclusions: These results not only explain the cell pathological mechanisms inhibiting phenotype differentiation in cells expressing HLD3-associated mutants but also identify the first chemical that restores such cells in vitro.
Formation and Properties of Amorphous Multi-Component (CrFeMoNbZr)Ox Thin Films
Authors: Gu Xiaoyu , Luan Hengwei , Yang Xinglong , Wang Xinchao , Fang Kaixuan , Li Jinfeng , Jia Yuzhen , Yao Kefu , Zhang Zhengjun , Chen Na
Published: May 2020

In this work, a new multi-component (CrFeMoNbZr)Ox system was developed. The thin films presented dual-phase amorphous structures, comprising a dominant amorphous alloy phase and a small amount of an amorphous oxide phase. The thin films showed higher hardness and better corrosion resistance than a commercial Zr-based alloy. The combined properties of high hardness and superior corrosion-resistance make the amorphous thin film a candidate for coating materials on commercial Zr-based alloys for engineering applications.
Does Intra-Wound Vancomycin Powder Affect the Action of Intra-Articular Tranexamic Acid in Total Joint Replacement?
Authors: Koutalos Antonios A. , Drakos Athanasios , Fyllos Apostolos , Doxariotis Nikos , Varitimidis Sokratis , Malizos Konstantinos N.
Published: May 2020

The intra-articular use of tranexamic acid (TXA) has contributed to reduced blood loss in total joint arthroplasty (TJA). The purpose of this study is to assess the efficacy of simultaneously topical use of tranexamic acid and vancomycin powder within the TJA space. From 2016 to 2017, 219 consecutive total hip arthroplasties (THAs) and 272 total knee arthroplasties (TKAs) were performed in a tertiary care center, with a group of patients receiving intra-articular TXA and vancomycin, compared to patients receiving only TXA and to a control group that did not receive anything. Haemoglobin and hematocrit were measured preoperatively, on the first and third days. Transfusions and adverse events were recorded. Haemoglobin and hematocrit dropped significantly in all THA and TKA groups till the third day postoperatively, with a major reduction in the control group, compared to the other two treatment groups. Infections and thromboembolic events were similar in either group of the TJAs. In conclusion, the topical use of tranexamic acid mixed with the vancomycin powder within the joint space after the TJAs of the hip and knee did not alter the anti-fibrinolytic effect of TXA.
The Quaternization Reaction of 5-O-Sulfonates of Methyl 2,3-o-Isopropylidene-β-D-Ribofuranoside with Selected Heterocyclic and Aliphatic Amines
Authors: Dmochowska Barbara , Ślusarz Rafał , Chojnacki Jarosław , Samaszko-Fiertek Justyna , Madaj Janusz
Published: May 2020

The synthesis of N-((methyl 5-deoxy-2,3-O-isopropylidene-β-D-ribofuranoside)-5-yl)ammonium salts are presented. To determine the effect of the nucleophile type and outgoing group on the quaternization reaction, selected aliphatic and heterocyclic aromatic amines reacted with: methyl 2,3-O-isopropylidene-5-O-tosyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside or methyl 2,3-O-isopropylidene-5-O-triflyl-β-D-ribofuranoside were performed on a micro scale. High-resolution 1H- and 13C-NMR spectral data for all new compounds were recorded. Additionally, the single-crystal X-ray diffraction analysis for methyl 2,3-O-isopropylidene-5-O-mesyl-β-D-ribofuranoside and selected in silico interaction models are reported.
Enhanced Low-Neutron-Flux Sensitivity Effect in Boron-Doped Silicon
Authors: Yang Guixia , Wu Kunlin , Liu Jianyong , Zou Dehui , Li Junjie , Lu Yi , Lv Xueyang , Xu Jiayun , Qiao Liang , Liu Xuqiang
Published: May 2020

Space particle irradiation produces ionization damage and displacement damage in semiconductor devices. The enhanced low dose rate sensitivity (ELDRS) effect caused by ionization damage has attracted wide attention. However, the enhanced low-particle-flux sensitivity effect and its induction mechanism by displacement damage are controversial. In this paper, the enhanced low-neutron-flux sensitivity (ELNFS) effect in Boron-doped silicon and the relationship between the ELNFS effect and doping concentration are further explored. Boron-doped silicon is sensitive to neutron flux and ELNFS effect could be greatly reduced by increasing the doping concentration in the flux range of 5 × 109–5 × 1010 n cm−2 s−1. The simulation based on the theory of diffusion-limited reactions indicated that the ELNFS in boron-doped silicon might be caused by the difference in the concentration of remaining vacancy-related defects (Vr) under different neutron fluxes. The ELNFS effect in silicon becomes obvious when the (Vr) is close to the boron doping concentration and decreased with the increase in boron doping concentration due to the remaining vacancy-related defects being covered. These conclusions are confirmed by the p+-n-p Si-based bipolar transistors since the ELNFS effect in the low doping silicon increased the reverse leakage of the bipolar transistors and the common-emitter current gain (β) dominated by highly doped silicon remained unchanged with the decrease in the neutron flux. Our work demonstrates that the ELNFS effect in boron-doped silicon can be well explained by noise diagnostic analysis together with electrical methods and simulation, which thus provide the basis for detecting the enhanced low-particle-flux damage effect in other semiconductor materials.
Magneto-Liposomes as MRI Contrast Agents: A Systematic Study of Different Liposomal Formulations
Authors: Kostevšek Nina , Cheung Calvin C. L. , Serša Igor , Kreft Mateja Erdani , Monaco Ilaria , Comes Franchini Mauro , Vidmar Janja , Al-Jamal Wafa T.
Published: May 2020

The majority of the clinically approved iron oxide nanoparticles (IO NPs) used as contrast agents for magnetic resonance imaging (MRI) have been withdrawn from the market either due to safety concerns or lack of profits. To address this challenge, liposomes have been used to prepare IO-based T2 contrast agents. We studied the influence of different phospholipids on the relaxivity (r2) values of magneto-liposomes (MLs) containing magnetic NPs in the bilayer, where a strong correlation between the bilayer fluidity and r2 is clearly shown. Embedding 5-nm IO NPs in the lipid bilayer leads to a significant improvement in their relaxivity, where r2 values range from 153 ± 5 s−1 mM−1 for DPPC/cholesterol/DSPE-PEG (96/50/4) up to 673 ± 12 s−1 mM−1 for DOPC/DSPE-PEG (96/4), compared to “free” IO NPs with an r2 value of 16 s−1 mM−1, measured at 9.4 T MRI scanner. In vitro MRI measurements, together with the ICP-MS analysis, revealed MLs as highly selective contrast agents that were preferentially taken up by cancerous T24 cells, which led to an improvement in the contrast and an easier distinction between the healthy and the cancerous cells. A careful selection of the lipid bilayer to prepare MLs could offer efficient MRI contrast agents, even at very low IO NP concentrations.
Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress
Authors: Carr Anitra C. , Spencer Emma , Dixon Liane , Chambers Stephen T.
Published: May 2020

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the Intensive Care Unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and hematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, an established marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs. 56 ± 24 µmol/L, p < 0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs. 24 ± 14 µmol/L, p = 0.02). The pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (p < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples from 28% of the cohort (mean 2.7 ± 1.7 days; range 1–7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (p = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease excessive oxidative stress and aid in their recovery.
Efficacy of Commercially Available Nutritional Supplements: Analysis of Serum Uptake, Macular Pigment Optical Density and Visual Functional Response
Authors: Bone Richard A. , Davey Pinakin Gunvant , Roman Betzabe O. , Evans David W.
Published: May 2020

Purpose: To compare the change in serum carotenoids, macular pigment optical density (MPOD) and visual function with the intake of two commercially available nutritional supplements. Methods: Participants were given a 24-week supply of a lipid-based micronized liquid medical food, Lumega-Z™ (LM), containing 28 mg of the macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ), or given PreserVision™ AREDS 2 Formula (gel-caps; PV) containing 12 mg of the macular carotenoids L and Z, but no reported MZ. Serum levels of L, Z and MZ were obtained at baseline and after 12 weeks. Macular pigment optical densities (MPOD) and visual function were assessed at baseline and after 24 weeks. Results: Average blood serum concentrations of L, Z and MZ in the two groups at baseline were similar. The increases in L, Z and MZ were 0.434, 0.063 and 0.086 µmol/L vs. 0.100, 0.043 and 0.001 µmol/L, respectively, in the LM vs. PV group. From baseline to week 24, average MPOD in the LM-group increased by 0.064 from 0.418 to 0.482, whereas in the PV-group, it was essentially unchanged (0.461 to 0.459;). Although log-contrast sensitivity was improved in all groups under three conditions (photopic, mesopic and mesopic with glare), the change in log-contrast sensitivity was not statistically significant. Conclusion: Despite only a 2.3-fold higher carotenoid concentration than PV, LM supplementation provides approximately 3–4-fold higher absorption, which leads to a significant elevation of MPOD levels.
A Low-Glycemic Index, High-Fiber, Pulse-Based Diet Improves Lipid Profile, but Does Not Affect Performance in Soccer Players
Authors: Mizelman Eliran , Chilibeck Philip D. , Hanifi Abdul , Kaviani Mojtaba , Brenna Eric , Zello Gordon A.
Published: May 2020

Pulses (i.e., lentils, chickpeas, beans, peas) are low-glycemic index, high-fiber foods that are beneficial for improving blood lipids. Young soccer players typically have low dietary fiber intake, perhaps because of concerns regarding gastro-intestinal problems during exercise performance. Twenty-seven (17 females) soccer players were randomized to receive a pulse-based diet or their regular diet for four weeks in a cross-over study and evaluated for changes in blood lipids and athletic performance, with 19 (22 ± 6y; 12 females) completing the study (eight participants withdrew because of lack of time). Women increased high density lipoproteins (+0.5 ± 0.7 vs. −0.6 ± 0.3 mmol/L; p < 0.01) and reduced total cholesterol to high density lipoprotein ratio (−2.4 ± 2.9 vs. +2.6 ± 2.2; p < 0.01) on the pulse-based vs. regular diet, respectively, while there were no differences between diet phases in men. Athletic performance assessed by distance covered during games by a global positioning system was not significantly different during the pulse-based vs. regular diet (9180 ± 1618 vs. 8987 ± 1808 m per game; p = 0.35). It is concluded that a pulse-based diet can improve blood lipid profile without affecting athletic performance in soccer players.
Genomic Comparison of Salmonella Enteritidis Strains Isolated from Laying Hens and Humans in the Abruzzi Region during 2018
Authors: Di Marcantonio Lisa , Janowicz Anna , Zilli Katiuscia , Romantini Romina , Bilei Stefano , Paganico Daniela , Persiani Tiziana , Di Donato Guido , Di Giannatale Elisabetta
Published: May 2020

Salmonellosis is a major cause of bacterial foodborne infection. Since 2016, an increased number of cases of gastroenteritis caused by Salmonella enterica serovar Enteritidis linked to eggs produced in Poland has been reported in Europe. In Italy, S. Enteritidis is one of the three most commonly reported serotypes, associated mainly with the consumption of contaminated eggs and derived products. In our work, we analysed 61 strains of S. Enteritidis obtained from humans and farms in the Abruzzi region, Italy, in 2018. We used Multiple-Loci Variable-Number Tandem Repeat (VNTR) analysis (MLVA)-based typing and Whole-Genome Sequencing (WGS) tools to identify closely related strains and perform cluster analysis. We found two clusters of genetically similar strains. The first one was present in the local farms and isolated from human cases and had single-linkage distance of no more than two core genes and less than five Single-Nucleotide Polymorphisms (SNPs). The second cluster contained strains isolated from humans and from a dessert (tiramisù) sample that shared identical core genome and were assigned the same SNP address. Cluster 2 isolates were found to be genetically similar to an S. Enteritidis strain from a multi-country outbreak linked to Polish eggs.
Gel Formulation of Nabumetone and a Newly Synthesized Analog: Microemulsion as a Photoprotective Topical Delivery System
Authors: Grande Fedora , Ragno Gaetano , Muzzalupo Rita , Occhiuzzi Maria Antonietta , Mazzotta Elisabetta , De Luca Michele , Garofalo Antonio , Ioele Giuseppina
Published: May 2020

Photostability studies were performed on topical formulations containing the anti-inflammatory drug Nabumetone and an analog newly synthesized in order to achieve better photostability and pharmacokinetic profile. Stability tests, according to the International Conference on Harmonization rules, were applied on ethanol solutions and topical gel formulations of both compounds. The photodegradation profiles were monitored by Multivariate curve resolution applied to the UV spectral data. The inclusion of the compounds in microemulsion was investigated to improve light stability and, at the same time, to ensure a sustained release system for skin delivery. All the formulations in solution, gel, microemulsion, and microemulsion-in-gel were exposed to a forced irradiation of 350 W/m2, corresponding to a 21 kJ/m2 min, for up to 300 min. Photostability increased significantly for both drugs in the liquid microemulsion and microemulsion-in-gel, compared to the ethanol solution and plain gel, reaching a residual drug of 97% and 98% for Nabumetone and analog in microemulsion-in-gel, respectively. Permeation experiments on the microemulsion-in-gel showed a better performance of the analog formulated at 0.2%, compared to the same formulation of Nabumetone at 0.7%. These results highlight the potential of the designed matrices as delayed drug delivery systems along with the use of lower drug doses leading to reduced side effects.
Physical Properties of an Ionic Liquid Composed of Two Water-Soluble Vitamins and Enhanced Skin Permeation of Both Vitamins
Authors: Sugibayashi Kenji , Yoshida Yuya , Suzuki Ryuichiro , Yoshizawa Kota , Mori Kenji , Itakura Shoko , Takayama Kozo , Todo Hiroaki
Published: May 2020

A highly viscous substance was prepared by evaporating an ethanol solution containing two hydrophilic vitamins; vitamin C, and vitamin B6. The viscous substance and physical mixture of the two vitamins were tested using a differential scanning calorimeter and an X-ray diffractometer. The highly viscous substance was found to be a liquid crystal (LC) made of these two hydrophilic vitamins. Determination by proton nuclear magnetic resonance measurement suggested that intramolecular hydrogen bonding in vitamin B6 was eliminated by the LC formation. This LC compound showed high solubility in 1,3-butanediol (almost 87%). Much higher skin permeation of both vitamin C and B6 was also observed from the LC compound than that from the physical mixture. The present LC compound containing vitamin C and vitamin B6 may be useful for pharmaceutical and cosmeceutical applications.
Bioinformatics Resources for Plant Abiotic Stress Responses: State of the Art and Opportunities in the Fast Evolving -Omics Era
Authors: Ambrosino Luca , Colantuono Chiara , Diretto Gianfranco , Fiore Alessia , Chiusano Maria Luisa
Published: May 2020

Abiotic stresses are among the principal limiting factors for productivity in agriculture. In the current era of continuous climate changes, the understanding of the molecular aspects involved in abiotic stress response in plants is a priority. The rise of -omics approaches provides key strategies to promote effective research in the field, facilitating the investigations from reference models to an increasing number of species, tolerant and sensitive genotypes. Integrated multilevel approaches, based on molecular investigations at genomics, transcriptomics, proteomics and metabolomics levels, are now feasible, expanding the opportunities to clarify key molecular aspects involved in responses to abiotic stresses. To this aim, bioinformatics has become fundamental for data production, mining and integration, and necessary for extracting valuable information and for comparative efforts, paving the way to the modeling of the involved processes. We provide here an overview of bioinformatics resources for research on plant abiotic stresses, describing collections from -omics efforts in the field, ranging from raw data to complete databases or platforms, highlighting opportunities and still open challenges in abiotic stress research based on -omics technologies.
Effect of Leaf Litter from Cistus ladanifer L. on the Germination and Growth of Accompanying Shrubland Species
Authors: Gallego Juan Carlos Alías , Caro Jonás González , Campos Virginia Hinojal , Lobón Natividad Chaves
Published: May 2020

Most communities with the presence of Cistus ladanifer are characterised by the low richness of accompanying species, with C. ladanifer, in most cases, exceeding 70% of the coverage of woody species. This fact could be due to the allelopathic activity attributed to compounds present in the leaves of C. ladanifer, which may have a negative effect on the germination and growth of woody species that share its habitat. One of the possible ways of incorporating allelopathic compounds to the soil is the degradation of leaf litter. Therefore, the aim of this study was to determine how the presence of leaf litter from C. ladanifer affects accompanying species. Under controlled conditions, we analysed the effect of C. ladanifer leaf litter on the germination and growth of seedlings of five species that share their habitat with C. ladanifer (Retama sphaerocarpa, Cytisus multiflorus, Lavandula stoechas, Cistus salviifolius, and Cistus crispus). Additionally, the effect of leaf litter on the species itself, C. ladanifer, has been studied. The experiments were designed with different concentrations of leaf litter (UL) and leaf litter from which the compounds with allelopathic activity were extracted (WL). The results show that such effect greatly depends on the analysed species, with L. stoechas being the most negatively affected species. On the other hand, C. multiflorus and C. salviifolius were only negatively affected at the stage of seedling growth. The results reveal the involvement of leaf litter in the allelopathic activity attributed to C. ladanifer and that its presence has a negative influence on the germination and growth of accompanying woody species. This shows the need to delve into the potential relevance of allelopathy as an interaction that determines the composition, structure and dynamics of a community.
Influence of the Land Use Type on the Wild Plant Diversity
Authors: Aneva Ina , Zhelev Petar , Lukanov Simeon , Peneva Mariya , Vassilev Kiril , Zheljazkov Valtcho D.
Published: May 2020

Studies on the impact of agricultural practices on plant diversity provide important information for policy makers and the conservation of the environment. The aim of the present work was to evaluate wild plant diversity across the agroecosystems in two contrasting regions of Bulgaria; Pazardzhik-Plovdiv (representing agroecosystems in the lowlands) and Western Stara Planina (the Balkan Mountains, representing agroecosystems in the foothills of the mountains). This study conducted a two-year assessment of plant diversity in different types of agricultural and forest ecosystems, representing more than 30 land use types. Plant diversity, measured by species number, was affected by the land use type only in Pazardzhik-Plovdiv region. More pronounced was the effect of the groups of land use types on the diversity, measured by the mean species number per scoring plot. Climatic conditions, measured by 19 bioclimatic variables, were the most important factor affecting plant species diversity. Six bioclimatic variables had a significant effect on the plant diversity, and the effect was more pronounced when the analysis considered pooled data of the two regions. The highest plant diversity was found on grazing land with sparse tree cover, while the lowest one was in the land use types representing annual crops or fallow. The study also established a database on weed species, relevant to agriculture. A number of common weeds were found in the Pazardzhik-Plovdiv region, while the most frequent species in the Western Stara Planina region were indigenous ones. Overall, the natural flora of Western Stara Planina was more conserved; eleven orchid species with conservation significance were found in the pastures and meadows in that region. The present study is the first attempt in Bulgaria to characterize the plant diversity across diverse agroecosystems representing many different land use types and environmental conditions. The results can contribute to nature conservation, biodiversity, and the sustainable use of plant resources.