bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio-Compatibility and Bio-Insulation of Implantable Electrode Prosthesis Ameliorated by A-174 Silane Primed Parylene-C Deposited Embedment
Authors: Lin Chin-Yu , Lou Wan-Shiun , Chen Jyh-Chern , Weng Kuo-Yao , Shih Ming-Cheng , Hung Ya-Wen , Chen Zhu-Yin , Wang Mei-Chih
Published: November 2020

Microelectrodes for pain management, neural prosthesis or assistances have a huge medical demand, such as the application of pain management chip or retinal prosthesis addressed on age-related macular degeneration (AMD) and the retinitis pigmentosa (RP). Due to lifelong implanted in human body and direct adhesion of neural tissues, the electrodes and associated insulation materials should possess an ideal bio-compatibility, including non-cytotoxicity and no safety concern elicited by immune responses. Our goal intended to develop retinal prosthesis, an electrical circuit chip used for assisting neural electrons transmission on retina and ameliorating the retinal disability. Therefore, based on the ISO 10993 guidance for implantable medical devices, the electrode prosthesis with insulation material has to conduct bio-compatibility assessment including cytotoxicity, hemolysis, (skin) irritation and pathological implantation examinations. In this study, we manufactured inter-digitated electrode (IDE) chips mimic the electrode prosthesis through photolithography. The titanium and platinum composites were deposited onto a silicon wafer to prepare an electric circuit to mimic the electrode used in retinal prosthesis manufacture, which further be encapsulated to examine the bio-compatibility in compliance with ISO 10993 and ASTM guidance specifically for implantable medical devices. Parylene-C, polyimide and silicon carbide were selected as materials for electrode encapsulation in comparison. Our data revealed parylene-C coating showed a significant excellence on bio-insulation and bio-compatibility specifically addressed on implantable neuron stimulatory devices and provided an economic procedure to package the electrode prosthesis. Therefore, parylene C encapsulation should serve as a consideration for future application on retinal prosthesis manufacture and examination.
Phosphogypsum and Black Steel Slag as Additives for Ecological Bentonite-Based Materials: Microstructure and Characterization
Authors: Harrou Achraf , Gharibi El Khadir , Taha Yassine , Fagel Nathalie , El Ouahabi Meriam
Published: November 2020

The Black Steel slag (Ss) and phosphogypsum (PG) are industrial wastes produced in Morocco. In order to reduce these two wastes and to evaluate their pozzolanic reactivity in the presence of water, they were incorporated into bentonite (B) mixed with lime (L). The studied mixtures (BLW, BL–PG–W and BL–PG–Ss–W) were analyzed by X-ray diffraction, Infrared spectroscopy, Raman spectroscopy and SEM/EDX analysis. Compressive strength tests were performed on hardened specimens. The results obtained show that the hydration kinetics of the B–L–W and B–L–PG–W mixtures are slow. The addition of PG to a bentonite––lime mixture induces the formation of new microstructures such as hydrated calcium silicate (C–S–H) and ettringite, which increases the compressive strength of the cementitious specimens. The addition of the Ss to a mixture composed of 8%PG and 8%L–B accelerates the kinetics of hydration and activates the pozzolanic reaction. The presence of C2S in the slag helps to increase the mechanical strength of the mixture B–L–PG–Ss. The compressive strength of the mixtures BL–W, BL–PG–W and BL–PG–Ss–W increases from 15 to 28 days of setting. After 28 days of setting, 8% of Sc added to the mixture 8% PG–8%L–B is responsible for an increase of the compressive strength to 0.6 MPa.
Evaluation of Deformation Temperatures in Carbonate Mylonites at Low Temperature Thrust-Tectonic Settings via Micro-Raman Spectroscopy
Authors: Croce Alessandro , Pigazzi Enrico , Fumagalli Patrizia , Rinaudo Caterina , Zucali Michele
Published: November 2020

Carbonaceous materials (CMs) have been widely used to assess temperatures in sedimentary and metamorphic carbonate rocks. The use of Raman spectroscopy of carbonaceous material (RSCM) is largely devoted to the study of deformed rocks hosted in thrust-tectonic settings. Raman spectroscopy of carbonaceous material successfully allows the study of carbonate rocks at a temperature as high as 650 °C. In this study, a set of carbonate-mylonite rocks (Italian Alps) were investigated using micro-Raman spectroscopy, in order to infer the deformation conditions associated with the Alpine thrusts, expected to occur at T < 350 °C. Micro-Raman spectra were collected using two sources: green (532 nm) and red (632.8 nm) lasers. Several deconvolution procedures and parameters were tested to optimize the collected spectrum morphologies for the laser sources, also in accordance with the low temperature expected. The obtained temperatures highlight two clusters: one at 340–350 °C for the samples collected in the axial part of the Alpine chain, and the other at 200–240 °C for those collected in the external thrust-and-fold belt. These results agree with the independent geological and petrological constraints. Consistent results were obtained using 532 and 632.8 nm laser sources when the appropriate deconvolution approach was used.
Geochronology, Geochemistry, and Geodynamic Relationship of the Mafic Dykes and Granites in the Qianlishan Complex, South China
Authors: Yu Zhi-Feng , Peng Qi-Ming , Zhao Zheng , Wang Ping-An , Xia Ying , Wang Yu-Qi , Wang Hao
Published: November 2020

The Qianlishan complex, located in Hunan Province of South China, is closely associated with intense W-dominated polymetallic mineralization. The Qianlishan complex is composed of three phases: the main-phase porphyritic and equigranular granites, granite porphyry, and mafic dykes. Geochronologically, the zircon U-Pb dating results show that the porphyritic and equigranular granites have ages of approximately 159 and 158 Ma, respectively, similar to those of mafic dykes (approximately 158 Ma), while the granite porphyry was formed later at approximately 145 Ma. Geochemically, the mafic dykes are characterized by calc-alkaline high-Mg andesite (HMA) with high MgO, TiO2, Mg#, and CA/TH index. They exhibit significantly depleted εNd(t) and εHf(t) with high Ba/La, La/Nb, and (La/Yb)N, indicating that they formed from mixing melts of depleted asthenospheric mantle and metasomatized subcontinental lithospheric mantle (SCLM). The main-phase granites are peraluminous and are characterized by high SiO2, low (La/Yb)N ratios, and relative depletion in Ba, Sr, Ti, and Eu. They also display negative correlations between La, Ce, Y, and Rb contents, suggesting that they are highly fractionated S-type granites. Furthermore, they show high εNd(t) and εHf(t), CaO/Na2O ratios, HREE, and Y contents, indicating that they were produced by parental melting of ancient basement mixed with mantle-derived components. In contrast, the granite porphyry shows A-type signature granites, with higher εNd(t) and εHf(t) and CaO/Na2O ratios than the main-phase granites but similar Zr/Nb and Zr/Hf ratios to the mafic dykes, suggesting that they are the products of partial melting of a hybrid source with ancient basement and the mafic dykes. We thus infer that the slab roll-back led to generation of Qianlishan back-arc basalt and HMA and further triggered the formation of the Qianlishan granite.
Field Emission Air-Channel Devices as a Voltage Adder
Authors: Chang Wen-Teng , Cheng Ming-Chih , Chuang Tsung-Ying , Tsai Ming-Yen
Published: November 2020

Field emission air-channel (FEAC) devices can work under atmospheric pressure with a low operation voltage when the electron channel is far less than the mean free path (MFP) in the air, thereby making them a practical component in circuits. Forward and reverse electron emissions of the current FEAC devices demonstrated symmetric Fowler–Nordheim (F–N) plots owing to the symmetric cathode and anode electrodes. This research aimed to demonstrate the arithmetic application of the FEAC devices, their substrate effect, and reliability. A voltage adder was composed of two FEAC devices whose two inputs were connected to two separate function generators, and one output was wire-connected to an oscilloscope. The devices were on a thin dielectric film and low-resistivity silicon substrate to evaluate the parasitic components and substrate effect, resulting in frequency-dependent impedance. The results show that the FEAC devices possessed arithmetic function, but the output voltage decreased. The FEAC devices were still capable of serving as a voltage adder after the reliability test, but electric current leakage increased. Finite element analysis indicated that the highest electrical fields and electron trajectories occur at the apices where the electrons travel with the shortest route less than the MFP in the air, thereby meeting the FEAC devices’ design. The modeling also showed that a sharp apex would generate a high electric field at the tip-gap-tip, enhancing the tunneling current.
Green Synthesis of Silver Nanoparticles Using Astragalus tribuloides Delile. Root Extract: Characterization, Antioxidant, Antibacterial, and Anti-Inflammatory Activities
Authors: Sharifi-Rad Majid , Pohl Pawel , Epifano Francesco , Álvarez-Suarez José M.
Published: November 2020

Today, the green synthesis of metal nanoparticles is a promising strategy in material science and nanotechnology. In this research, silver nanoparticles (AgNPs) were synthesized through the high-efficient, cost-effective green and facile process, using the Astragalus tribuloides Delile. root extract as a bioreduction and capping agent at room temperature. UV–Vis spectroscopy was applied for the investigation of the reaction proceedings. To characterize the greenly synthesized AgNPs, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), and transmission electron microscopy (TEM) analyses were utilized. In addition, the total phenolics and flavonoids contents, antioxidant, antibacterial, and anti-inflammatory activities of the greenly synthesized AgNPs and the A. tribuloides root extract were evaluated. The results indicated that the AgNPs had spherical morphology and crystalline structure with the average size of 34.2 ± 8.0 nm. The total phenolics and flavonoids contents of the greenly synthesized AgNPs were lower than those for the A. tribuloides root extract. The resultant AgNPs exhibited the appropriate antioxidant activity (64%) as compared to that for the A. tribuloides root extract (47%). The antibacterial test approved the higher bactericidal activity of the resulting AgNPs on the Gram-positive and Gram-negative bacteria in comparison to the A. tribuloides root extract. Considering the anti-inflammatory activity, the greenly synthesized AgNPs showed a stranger effect than the A. tribuloides root extract (82% versus 69% at 500 μg/mL). Generally, the AgNPs that were fabricated by using the A. tribuloides root extract had appropriate antioxidant, antibacterial, and anti-inflammatory activities and, therefore, can be considered as a promising candidate for various biomedical applications.
Effects of Nutrition Education Interventions in Team Sport Players. A Systematic Review
Authors: Sánchez-Díaz Silvia , Yanci Javier , Castillo Daniel , Scanlan Aaron T. , Raya-González Javier
Published: November 2020

Considering nutrition education interventions have been frequently implemented in team sport athletes and have shown promising results, this study aimed to summarize the effects of nutrition education interventions on eating habits, nutrition knowledge, body composition, and physical performance in team sport athletes. A systematic review was conducted using the following databases: PubMed/MEDLINE, Web of Science and SPORTDiscus. A total of 14 studies met the inclusion criteria for the review. The methodological quality of included studies was evaluated, and each study was assessed according to the analyzed variables (i.e., eating habits, nutrition knowledge, body composition, and physical performance). Most studies showed improvements in or maintenance of variables used to indicate eating habits, nutrition knowledge, and body composition. However, limited studies examined the effect of nutrition education interventions on physical performance, with existing studies demonstrating disparate results. These findings suggest implementation of nutrition education interventions in team sport athletes could be an effective strategy to improve their eating habits, nutrition knowledge, and body composition. Due to the heterogeneity across the included studies regarding sport modality, competition level, age, and sex of the athletes investigated, as well as the intervention type adopted (i.e., online or face-to-face), it is difficult to establish optimal nutrition education interventions for each analyzed variable.
An Anthocyanin-Rich Extract Obtained from Portuguese Blueberries Maintains Its Efficacy in Reducing Microglia-Driven Neuroinflammation after Simulated Digestion
Authors: Serra Diana , Henriques Joana F. , Serra Teresa , Bento Silva Andreia , Bronze Maria Rosário , Dinis Teresa C. P. , Almeida Leonor M.
Published: November 2020

Dietary polyphenols are multi-target compounds that have been considered promising candidates in strategies for the mitigation of neurological diseases, acting particularly through reduction of microglia-driven neuroinflammation. In this study, an anthocyanin-rich extract obtained from Portuguese blueberries was subjected to a simulated gastrointestinal digestion; after chemical characterisation, the potential of both non-digested and digested extracts to combat neuroinflammation was evaluated using a microglia N9 cell line. Although the extracts have markedly different chemical composition, both were efficient in reducing the production of either key inflammatory markers or reactive oxygen species and in enhancing reduced glutathione levels in activated cells. Furthermore, this protection was shown to be related to the suppression of nuclear factor kappa B (NF-kB) activation, and to a signal transducer and activator of transcription 1 (STAT1)-independent mechanism. These results demonstrate that the anthocyanin extract, after simulated digestion, maintains its efficacy against neuroinflammation, and can, therefore, assume a relevant role in prevention of neuroinflammation-related neurological disorders.
The Benefits of Including Hummus and Hummus Ingredients into the American Diet to Promote Diet Quality and Health: A Comprehensive Review
Authors: Reister Evan J. , Belote Lynn N. , Leidy Heather J.
Published: November 2020

Over the last decade, hummus has become an increasingly popular food. Given the ingredients (i.e., primarily chickpeas and tahini), nutrient composition, versatility, and acceptability, hummus can play a unique role when included in the American diet, to promote diet quality and improve health. The purpose of this paper is to provide a comprehensive review of the scientific evidence examining the effects of acute and long-term consumption of hummus and hummus ingredients on diet quality and risk factors related to type 2 diabetes, cardiovascular disease, and obesity. In addition, food pattern/menu modeling is included to illustrate the potential nutritional impact of consuming hummus to meet dietary guidelines. In general, the consumption of hummus and/or its respective ingredients has been shown to improve postprandial glycemic control, fasting lipids, appetite control, and daily food intake compared to other commonly consumed foods. The incorporation of hummus into the American diet can also improve diet quality by replacing foods higher in saturated fats, sodium, or added sugars. Collectively, these findings support the addition of hummus and/or hummus ingredients as an important component of a healthy dietary pattern.
Dietary Habits and Risk of Early-Onset Dementia in an Italian Case-Control Study
Authors: Filippini Tommaso , Adani Giorgia , Malavolti Marcella , Garuti Caterina , Cilloni Silvia , Vinceti Giulia , Zamboni Giovanna , Tondelli Manuela , Galli Chiara , Costa Manuela , Chiari Annalisa , Vinceti Marco
Published: November 2020

Risk of early-onset dementia (EOD) might be modified by environmental factors and lifestyles, including diet. The aim of this study is to evaluate the association between dietary habits and EOD risk. We recruited 54 newly-diagnosed EOD patients in Modena (Northern Italy) and 54 caregivers as controls. We investigated dietary habits through a food frequency questionnaire, assessing both food intake and adherence to dietary patterns, namely the Greek-Mediterranean, the Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. We modeled the relation between dietary factors and risk using the restricted cubic spline regression analysis. Cereal intake showed a U-shaped relation with EOD, with risk increasing above 350 g/day. A high intake (>400 g/day) of dairy products was also associated with excess risk. Although overall fish and seafood consumption showed no association with EOD risk, we found a U-shaped relation with preserved/tinned fish, and an inverse relation with other fish. Similarly, vegetables (especially leafy) showed a strong inverse association above 100 g/day, as did citrus and dry fruits. Overall, sweet consumption was not associated with EOD risk, while dry cake and ice-cream showed a positive relation and chocolate products an inverse one. For beverages, we found no relation with EOD risk apart from a U-shaped relation for coffee consumption. Concerning dietary patterns, EOD risk linearly decreased with the increasing adherence to the MIND pattern. On the other hand, an inverse association for the Greek-Mediterranean and DASH diets emerged only at very high adherence levels. To the best of our knowledge, this is the first study that explores the association between dietary factors and EOD risk, and suggests that adherence to the MIND dietary pattern may decrease such risk.
Relationship between Breastfeeding and Malocclusion: A Systematic Review of the Literature
Authors: Abate Andrea , Cavagnetto Davide , Fama Andrea , Maspero Cinzia , Farronato Giampietro
Published: November 2020

Background: The purpose of this systematic review was to analyze the available literature about the influence of breastfeeding in primary and mixed dentition on different types of malocclusions. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines were used to perform the present review. The following electronic databases were searched: Pubmed, Evidence-Based Medicine Reviews (EBMR), Embase, Cochrane Library, Medline, Web of Science and Ovid. Results: A primary research found a total of 279 articles. Two more papers were also considered from the gray literature. Two hundred sixty-three articles were excluded as they were deemed irrelevant on the basis of: duplicates, title, abstract, methods and/or irrelevant contents. Eighteen papers were selected and included in the qualitative analysis. Conclusions: breastfeeding is a positive factor that seems to reduce the incidence of posterior crossbite, skeletal class II and distoclusion in primary and mixed dentition. A sort of positive relationship between months of breastfeeding and risk reduction seems to exist. More longitudinal research is needed to avoid bias in the results, with data collected prospectively on the months of exclusive breastfeeding, by means of specific questionnaires and successive clinical evaluation of the occlusal condition at the primary dentition, mixed dentition and permanent dentition stages.
Dietary Pattern and Dietary Energy from Fat Associated with Sarcopenia in Community-Dwelling Older Chinese People: A Cross-Sectional Study in Three Regions of China
Authors: Li Cheng , Kang Bingxian , Zhang Ting , Gu Hongru , Song Pengkun , Chen Jingyi , Wang Xile , Xu Bin , Zhao Wenhua , Zhang Jian
Published: November 2020

Associations between dietary patterns (DPs) and sarcopenia remain controversial, and fewer studies have mentioned the relationship between dietary energy composition and sarcopenia. The present cross-sectional study was conducted in three regions of China, to detect the associations between DPs and sarcopenia, and to identify the influencing nutrients. Exploratory factor analysis was conducted for DP identification. Logistic regressions were performed to explore the associations between DPs and sarcopenia. Dietary nutrients and dietary energy composition were calculated and compared among different DPs. Three DPs were identified from 861 community-dwelling older people. The “mushrooms–fruits–milk” pattern was negatively associated with sarcopenia (OR = 0.33, 95% CI = 0.14~0.77, p-trend = 0.009). Subjects in the highest quartile of the “mushrooms–fruits–milk” pattern showed more abundant intake (1.7 g/kg/d) of dietary protein, and lower percentage (31%) of energy from fat (PEF) than the other two DPs. Further analyses indicated that lower PEF (<30%) was negatively associated with sarcopenia. In conclusion, the “mushrooms–fruits–milk” pattern was negatively associated with sarcopenia in community-dwelling older Chinese people. This pattern showed abundant protein intake and low PEF, which may partially contribute to its protective effect on sarcopenia. Therefore, besides protein, dietary fat and PEF may also be considered in the prevention and management of sarcopenia.
Trial Design in Critical Care Nutrition: The Past, Present and Future
Authors: Chapple Lee-anne S. , Ridley Emma J. , Chapman Marianne J.
Published: November 2020

The specialty of nutrition in critical care is relatively modern, and accordingly, trial design has progressed over recent decades. In the past, small observational and physiological studies evolved to become small single-centre comparative trials, but these had significant limitations by today’s standards. Power calculations were often not undertaken, outcomes were not specified a priori, and blinding and randomisation were not always rigorous. These trials have been superseded by larger, more carefully designed and conducted multi-centre trials. Progress in trial conduct has been facilitated by a greater understanding of statistical concepts and methodological design. In addition, larger numbers of potential study participants and increased access to funding support trials able to detect smaller differences in outcomes. This narrative review outlines why critical care nutrition research is unique and includes a historical critique of trial design to provide readers with an understanding of how and why things have changed. This review focuses on study methodology, population group, intervention, and outcomes, with a discussion as to how these factors have evolved, and concludes with an insight into what we believe trial design may look like in the future. This will provide perspective on the translation of the critical care nutrition literature into clinical practice.
DNA Methylation Profiles of Vegans and Non-Vegetarians in the Adventist Health Study-2 Cohort
Authors: Miles Fayth L. , Mashchak Andrew , Filippov Valery , Orlich Michael J. , Duerksen-Hughes Penelope , Chen Xin , Wang Charles , Siegmund Kimberly , Fraser Gary E.
Published: November 2020

We sought to determine if DNA methylation patterns differed between vegans and non-vegetarians in the Adventist Health Study-2 cohort. Genome-wide DNA methylation derived from buffy coat was profiled in 62 vegans and 142 non-vegetarians. Using linear regression, methylation of CpG sites and genes was categorized or summarized according to various genic/intergenic regions and CpG island-related regions, as well as the promoter. Methylation of genes was measured as the average methylation of available CpG’s annotated to the nominated region of the respective gene. A permutation method defining the null distribution adapted from Storey et al. was used to adjust for false discovery. Differences in methylation of several CpG sites and genes were detected at a false discovery rate < 0.05 in region-specific and overall analyses. A vegan diet was associated predominantly with hypomethylation of genes, most notably methyltransferase-like 1 (METTL1). Although a limited number of differentially methylated features were detected in the current study, the false discovery method revealed that a much larger proportion of differentially methylated genes and sites exist, and could be detected with a larger sample size. Our findings suggest modest differences in DNA methylation in vegans and non-vegetarians, with a much greater number of detectable significant differences expected with a larger sample.
Understanding the Heterogeneity of Obesity and the Relationship to the Brain-Gut Axis
Authors: Hung Tony K. W. , Dong Tien S. , Chen Zixi , Elashoff David , Sinsheimer Janet S. , Jacobs Jonathan P. , Lagishetty Venu , Vora Priten , Stains Jean , Mayer Emeran A. , Gupta Arpana
Published: November 2020

Obesity is best understood as a multifactorial metabolic imbalances disorder. In a cross-sectional study, we aimed to explore sociodemographic and dietary determinants of obesity in relation to brain-gut homeostasis among overweight and obese individuals. Multivariate logistic regression models were used to examine obesity and its association with sociodemographic and dietary factors. Biological variables examined included the gut microbiome, fecal amino acid metabolites and brain structural volumes. Among 130 participants, there were higher odds of obesity if individuals were Hispanic (adjusted odds ratio (aOR) 1.56, p = 0.014). Compared to non-Hispanics, Hispanics differed in gut microbial composition (p = 0.046) with lower microbial species richness (Chao1) (p = 0.032) and evenness (Shannon) (p = 0.0029). Fourteen of the twenty fecal amino acids including branch-chain- and aromatic- amino acids were increased among Hispanics (q < 0.05). Brain structural volumes in reward regions were decreased in Hispanics (pallidum, q = 0.036; brainstem, q = 0.011). Correlation patterns suggest complex brain-gut interactions differ by Hispanic ethnicity. In conclusion, Hispanics expressed a unique brain-gut microbial signature, which was associated with obesity despite sociodemographic and dietary differences. Addressing ethnic disparities guided by biologic phenotypes may unlock novel understanding of obesity heterogeneity and treatment strategies.
Lactobacillus sakei ADM14 Induces Anti-Obesity Effects and Changes in Gut Microbiome in High-Fat Diet-Induced Obese Mice
Authors: Won Sung-Min , Chen Siyu , Lee Seo Yeon , Lee Kyung Eun , Park Kye Won , Yoon Jung-Hoon
Published: November 2020

The aim of our study was to evaluate the anti-obesity effects of Lactobacillus sakei (L. sakei) ADM14 administration in a high-fat diet-induced obese mouse model and the resulting changes in the intestinal microbiota. Prior to in vivo testing, L. sakei ADM14 was shown to inhibit adipogenesis through in vitro test and genetic analysis. Subsequently, mice were orally administered 0.85% saline supplemented or not with L. sakei ADM14 to high-fat diet group and normal diet group daily. The results showed that administration of L. sakei ADM14 reduced weight gain, epididymal fat expansion, and total blood cholesterol and glucose levels, and significantly decreased expression of lipid-related genes in the epididymal fat pad. Administration of L. sakei ADM14 showed improvement in terms of energy harvesting while restoring the Firmicutes to Bacteroidetes ratio and also increased the relative abundance of specific microbial taxa such as Bacteroides faecichinchillae and Alistipes, which are abundant in non-obese people. L. sakei ADM14 affected the modulation of gut microbiota, altered the strain profile of short-chain fatty acid production in the cecum and enhanced the stimulation of butyrate production. Overall, L. sakei ADM14 showed potential as a therapeutic probiotic supplement for metabolic disorders, confirming the positive changes of in vivo indicators and controlling gut microbiota in a high-fat diet-induced obese mouse model.
Association between Serum Vitamin D Metabolites and Metabolic Function in Healthy Asian Adults
Authors: Ding Cherlyn , Chan Zhiling , Chooi Yu Chung , Choo John , Sadananthan Suresh Anand , Michael Navin , Velan Sambasivam Sendhil , Leow Melvin Khee-Shing , Magkos Faidon
Published: November 2020

The association between low vitamin D status and the development of type 2 diabetes mellitus is well established; however, intervention trials that increased serum vitamin D (through ultraviolet B exposure or dietary supplementation) provide mixed outcomes. Recent evidence suggests that metabolites directly related to vitamin D receptor activation—1α,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3—may be better markers of vitamin D repletion status. We tested the hypothesis that a vitamin D metabolite (VDM) index, calculated as the sum of normalized fasting serum concentrations of 1α,25-dihydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3, is associated with metabolic function. We measured subcutaneous and visceral adipose tissue volume, intrahepatic triglyceride content, maximum oxygen uptake, insulin sensitivity (4 h hyperinsulinemic-euglycemic clamp), and insulin secretion (3 h meal tolerance test with mathematical modeling) and calculated the VDM index in 65 healthy Asian adults. Subjects with a low VDM index had lower peripheral insulin sensitivity and beta-cell function compared to subjects with a high VDM index (both p < 0.05), matched for age, sex, BMI, and serum 25-hydroxyvitamin D3. Serum 25-hydroxyvitamin D3 was not associated with peripheral insulin sensitivity or beta-cell function. Our results suggest that, rather than enhancing vitamin D substrate availability, upregulation of vitamin D action is more likely to lead to improvements in glucose homeostasis.
Synthesis of Platinum(II) Complexes with Some 1-Methylnitropyrazoles and In Vitro Research on Their Cytotoxic Activity
Authors: Mastalarz Henryk , Mastalarz Agnieszka , Wietrzyk Joanna , Milczarek Magdalena , Kochel Andrzej , Regiec Andrzej
Published: November 2020

A series of eight novel platinum(II) complexes were synthesized by the reaction of the appropriate 1-methylnitropyrazole derivatives with K2PtCl4 and characterized by elemental analysis, ESI MS spectrometry, 1H NMR, 195Pt NMR, IR and far IR spectroscopy. Thermal isomerization of cis-dichloridobis(1-methyl-4-nitropyrazole)platinum(II) 1 to trans-dichloridobis(1-methyl-4-nitropyrazole)platinum(II) 2 has been presented, and the structure of the compound 2 has been confirmed by X-ray diffraction method. Cytotoxicity of the investigated compounds was examined in vitro on three human cancer cell lines (MCF-7 breast, ES-2 ovarian and A-549 lung adenocarcinomas) and their logP was measured using a shake-flask method. The trans complex 2 showed better antiproliferative activity than cisplatin for all the tested cancer cell lines. Additionally, trans-dichloridobis(1-methyl-5-nitropyrazole)platinum(II) 4 has featured a lower IC50 value than reference cisplatin against MCF-7 cell line. To gain additional information that may facilitate the explanation of the mode of action of tested compounds cellular platinum uptake, stability in L-glutathione solution, influence on cell cycle progression of HL-60 cells and ability to apoptosis induction were determined for compounds 1 and 2.
Synthesis, Biological, and Computational Evaluation of Antagonistic, Chiral Hydrobenzoin Esters of Arecaidine Targeting mAChR M1
Authors: Ozenil Marius , Aronow Jonas , Piljak Daniela , Vraka Chrysoula , Holzer Wolfgang , Spreitzer Helmut , Wadsak Wolfgang , Hacker Marcus , Pichler Verena
Published: November 2020

Muscarinic acetylcholine receptors (mAChRs) are a pivotal constituent of the central and peripheral nervous system. Yet, therapeutic and diagnostic applications thereof are hampered by the lack of subtype selective ligands. Within this work, we synthesized and chemically characterized three different stereoisomers of hydrobenzoin esters of arecaidine by NMR, HR-MS, chiral chromatography, and HPLC-logP. All compounds are structurally eligible for carbon-11 labeling and show appropriate stability in Dulbecco’s phosphate-buffered saline (DPBS) and F12 cell culture medium. A competitive radioligand binding assay on Chinese hamster ovary cell membranes comprising the human mAChR subtypes M1-M5 showed the highest orthosteric binding affinity for subtype M1 and a strong influence of stereochemistry on binding affinity, which corresponds to in silico molecular docking experiments. Ki values toward M1 were determined as 99 ± 19 nM, 800 ± 200 nM, and 380 ± 90 nM for the (R,R)-, (S,S)-, and racemic (R,S)-stereoisomer, respectively, highlighting the importance of stereochemical variations in mAChR ligand development. All three stereoisomers were shown to act as antagonists toward mAChR M1 using a Fluo-4 calcium efflux assay. With respect to future positron emission tomography (PET) tracer development, the (R,R)-isomer appears especially promising as a lead structure due to its highest subtype selectivity and lowest Ki value.
Curcumin In Situ Gelling Polymeric Insert with Enhanced Ocular Performance
Authors: Abdelkader Hamdy , Wertheim David , Pierscionek Barbara , Alany Raid G.
Published: November 2020

The search for an ocular drug delivery system that could provide long-acting effects without a detriment to the anatomy and physiology of the eye remains a challenge. Polyphenolic compounds (curcumin in particular) have recently gained popularity due to their powerful antioxidant properties; yet curcumin suffers poor stability and water solubility. A conventional eye drop formulation of curcumin in the form of a suspension is likely to suffer a short duration of action requiring multiple instillations. On the other hand, polymeric in-situ gelling inserts offer the prospect of overcoming these limitations. The aim of this study was to prepare, characterize and evaluate in vivo, polymeric, in-situ gelling and mucoadhesive inserts for ocular surface delivery of curcumin. Different types and ratios of biocompatible polymers (HPMC, CMC, PL 127 and PVA) and three plasticizers along with the solvent casting method were adopted to prepare curcumin inserts. The inserts were investigated for their physicochemical characteristics, applicability, and suitability of use for potential placement on the ocular surface. The prepared inserts revealed that curcumin was mainly dispersed in the molecular form. Insert surfaces remained smooth and uniform without cracks appearing during preparation and thereafter. Improved mechanical and mucoadhesive properties, enhanced in vitro release (7.5- to 9-fold increases in RRT300 min) and transcorneal permeation (5.4- to 8.86-fold increases in Papp) of curcumin was achieved by selected in-situ gelling inserts compared to a control curcumin suspension. The developed inserts demonstrated acceptable ocular tolerability, enhanced corneal permeability, and sustained release of curcumin along with retention of insert formulation F7 on the ocular surface for at least two-hours. This insert provides a viable alternative to conventional eye drop formulations of curcumin.
Nanostructured Polymeric, Liposomal and Other Materials to Control the Drug Delivery for Cardiovascular Diseases
Authors: Skourtis Dimitrios , Stavroulaki Dimitra , Athanasiou Varvara , Fragouli Panagiota G. , Iatrou Hermis
Published: November 2020

Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives each year, representing one third of global mortality. As existing therapies still have limited success, due to the inability to control the biodistribution of the currently approved drugs, the quality of life of these patients is modest. The advent of nanomedicine has brought new insights in innovative treatment strategies. For this reason, several novel nanotechnologies have been developed for both targeted and prolonged delivery of therapeutics to the cardiovascular system tο minimize side effects. In this regard, nanoparticles made of natural and/or synthetic nanomaterials, like liposomes, polymers or inorganic materials, are emerging alternatives for the encapsulation of already approved drugs to control their delivery in a targeted way. Therefore, nanomedicine has attracted the attention of the scientific community as a potential platform to deliver therapeutics to the injured heart. In this review, we discuss the current types of biomaterials that have been investigated as potential therapeutic interventions for CVDs as they open up a host of possibilities for more targeted and effective therapies, as well as minimally invasive treatments.
Enhanced Antisense Oligonucleotide Delivery Using Cationic Liposomes Grafted with Trastuzumab: A Proof-of-Concept Study in Prostate Cancer
Authors: Sicard Guillaume , Paris Clément , Giacometti Sarah , Rodallec Anne , Ciccolini Joseph , Rocchi Palma , Fanciullino Raphaëlle
Published: November 2020

Prostate cancer (PCa) is the second most common cancer in men worldwide and the fifth leading cause of death by cancer. The overexpression of TCTP protein plays an important role in castration resistance. Over the last decade, antisense technology has emerged as a rising strategy in oncology. Using antisense oligonucleotide (ASO) to silence TCTP protein is a promising therapeutic option—however, the pharmacokinetics of ASO does not always meet the requirements of proper delivery to the tumor site. In this context, developing drug delivery systems is an attractive strategy for improving the efficacy of ASO directed against TCTP. The liposome should protect and deliver ASO at the intracellular level in order to be effective. In addition, because prostate cancer cells express Her2, using an anti-Her2 targeting antibody will increase the affinity of the liposome for the cell and optimize the intratumoral penetration of the ASO, thus improving efficacy. Here, we have designed and developed pegylated liposomes and Her2-targeting immunoliposomes. Mean diameter was below 200 nm, thus ensuring proper enhanced permeation and retention (EPR) effect. Encapsulation rate for ASO was about 40%. Using human PC-3 prostate cancer cells as a canonical model, free ASO and ASO encapsulated into either liposomes or anti-Her2 immunoliposomes were tested for efficacy in vitro using 2D and 3D spheroid models. While the encapsulated forms of ASO were always more effective than free ASO, we observed differences in efficacy of encapsulated ASO. For short exposure times (i.e., 4 h) ASO liposomes (ASO-Li) were more effective than ASO-immunoliposomes (ASO-iLi). Conversely, for longer exposure times, ASO-iLi performed better than ASO-Li. This pilot study demonstrates that it is possible to encapsulate ASO into liposomes and to yield antiproliferative efficacy against PCa. Importantly, despite mild Her2 expression in this PC-3 model, using a surface mAb as targeting agent provides further efficacy, especially when exposure is longer. Overall, the development of third-generation ASO-iLi should help to take advantage of the expression of Her2 by prostate cancer cells in order to allow greater specificity of action in vivo and thus a gain in efficacy.
CD Oxyanions as a Tool for Synthesis of Highly Anionic Cyclodextrin Polymers
Authors: Girek Tomasz , Koziel Kinga , Girek Beata , Ciesielski Wojciech
Published: November 2020

Water soluble highly anionic β-cyclodextrin-based polymers were synthesized by reaction between cyclodextrin oxyanion and pyromellitic anhydride. The synthesis method utilizes activation hydroxyl groups in anhydrous glucopyranosyl units (AGU) in the DMF solution with the use of NaH. In these conditions, like in the case of the cyclodextrin reactions in the highly alkaline media, there is a nucleophilic substitution of difunctional compounds, which develops a polymer network with various cyclodextrin substitution. Different molar ratios of the reagents were investigated in terms of molecular size, chemical structure and water solubility of the polymers. The separation of the polymer due to particle size by ultrafiltration process and HPSEC-MALLS-RI and MALDI-TOF MS measurements for molecular mass analysis were employed. The IR, H NMR, SEM, DSC and TG measurements were taken for the structural characterization of the polymers. Additionally, the solubility test and metal ion complexation processes were also investigated in a wide range of pH. These polymers could be used in several areas such as: improving the aqueous solubility of poor water-soluble molecules, removing heavy metals from waste water, protecting degradable substances or synthesizing new drug delivery systems.
Identification and Quantitation Studies of Migrants from BPA Alternative Food-Contact Metal Can Coatings
Authors: Zhang Nan , Scarsella Joseph B. , Hartman Thomas G.
Published: November 2020

Bisphenol A (BPA)-based epoxy resins have wide applications as food-contact materials such as metal can coatings. However, negative consumer perceptions toward BPA have driven the food packaging industry to develop other alternatives. In this study, four different metal cans and their lids manufactured with different BPA-replacement food-contact coatings are subjected to migration testing in order to identify migratory chemical species from the coatings. Migration tests are conducted using food simulants and conditions of use corresponding to the intended applications and regulatory guidance from the U.S. Food and Drug Administration. Extracts are analyzed by gas chromatography mass spectrometry (GC-MS) and high resolution GC-MS. The migratory compounds identified include short chain cyclic polyester migrants from polyester-based coatings and bisphenol-type migrants including tetramethyl bisphenol F (TMBPF), tetramethyl bisphenol F diglycidyl ether (TMBPF DGE), bisphenol F (BPF), bisphenol C (BPC), and other related monomers or oligomers. The concentration of the migrants is estimated using an internal standard, and validated trimethylsilyl (TMS) derivatization GC-MS methods are developed to specifically quantify TMBPF, BPF, BPC, and BPA in the coatings. The results will aid the safety evaluation of new food-contact material coating technology based on TMBPF chemistry and will provide an important reference for the industry in identifying and quantifying non-BPA coating-borne migrants.
Bibliometric Analysis of Literature Published on Antibacterial Dental Adhesive from 1996–2020
Authors: Khan Abdul Samad , Ur Rehman Shafiq , AlMaimouni Yara Khalid , Ahmad Shakil , Khan Maria , Ashiq Murtaza
Published: November 2020

This study aimed to investigate the current state of research on antibacterial dental adhesives. The interest in this field can be drawn from an increasing number of scholarly works in this area. However, there is still a lack of quantitative measurement of this topic. The main aim of this study was to consolidate the research published on the antibacterial adhesive from 1996 to 2020 in Web of Science indexed journals. The bibliometric method, a quantitative study of investigating publishing trends and patterns, was used for this study. The result has shown that a gradual increase in research was found, whereby a substantial increase was observed from 2013. A total of 248 documents were published in 84 journals with total citations of 5107. The highly cited articles were published mainly in Q1 category journals. Most of the published articles were from the USA, China, and other developed countries; however, some developing countries contributed as well. The authorship pattern showed an interdisciplinary and collaborative approach among researchers. The thematic evaluation of keywords along with a three-factor analysis showed that ‘antibacterial adhesives’ and ‘quaternary ammonium’ have been used commonly. This bibliometric analysis can provide direction not only to researchers but also to funding organizations and policymakers.
Synthesis of Lactic Acid-Based Thermosetting Resins and Their Ageing and Biodegradability
Authors: Lopes Gomes Hastenreiter Lara , Ramamoorthy Sunil Kumar , Srivastava Rajiv K. , Yadav Anilkumar , Zamani Akram , Åkesson Dan
Published: November 2020

The present work is focused on the synthesis of bio-based thermoset polymers and their thermo–oxidative ageing and biodegradability. Toward this aim, bio-based thermoset resins with different chemical architectures were synthesized from lactic acid by direct condensation with ethylene glycol, glycerol and pentaerythritol. The resulting branched molecules with chain lengths (n) of three were then end-functionalized with methacrylic anhydride. The chemical structures of the synthesized lactic acid derivatives were confirmed by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT–IR) before curing. To evaluate the effects of structure on their properties, the samples were investigated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and the tensile testing. The samples went through thermo-oxidative ageing and biodegradation; and their effects were investigated. FT-IR and 1H-NMR results showed that three different bio-based resins were synthesized using polycondensation and end-functionalization. Lactic acid derivatives showed great potential to be used as matrixes in polymer composites. The glass transition temperature of the cured resins ranged between 44 and 52 °C. Pentaerythritol/lactic acid cured resin had the highest tensile modulus and it was the most thermally stable among all three resins. Degradative processes during ageing of the samples lead to the changes in chemical structures and the variations in Young’s modulus. Microscopic images showed the macro-scale surface degradation on a soil burial test.
“Spiritual Warfare” or “Crimes against Humanity”? Evangelized Drug Traffickers and Violence against Afro-Brazilian Religions in Rio de Janeiro
Authors: Boaz Danielle N.
Published: November 2020

Since at least 2005, drug traffickers in the cities and favelas of the state of Rio de Janeiro have been carrying out systematic and violent assaults on Afro-Brazilian religious communities. Motivated by their conversion to sects of Evangelical Christianity that regard Afro-Brazilian religions as devil worship, the traffickers have forcibly expelled devotees of these faiths from their homes and temples, destroyed shrines and places of worship, and threatened to kill priests if they continue to practice their religion. Scholars have often described this religious landscape as a “conflict” and a “spiritual war.” However, I argue that Evangelized drug traffickers and Afro-Brazilian religions are not engaged in a two-sided struggle; rather, the former is unilaterally committing gross violations of the latter’s human rights, which contravene international norms prohibiting crimes against humanity and genocide.