bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Dynamics Simulations on the Elastic Properties of Polypropylene Bionanocomposite Reinforced with Cellulose Nanofibrils
Authors: Modi Vaibhav , Karttunen Antti J.
Published: September 2022

Cellulose-reinforced polypropylene bionanocomposites can show improved elastic properties over their pure polypropylene counterparts. We have used equilibrium and non-equilibrium molecular dynamics (MD) simulations to study the elastic properties of polypropylene bionanocomposite systems composed of cellulose nanofibrils (CNF), polypropylene (PP) matrix, and maleic anhydride (MAH) coupling agent. The components of the bionanocomposite were parametrized for compatibility with the AMBER14SB force fields. The elastic properties of pure PP systems converge for the chains with at least 20 monomers. The ratio of cellulose in CNF-PP bionanocomposites strongly affects their elastic properties. The elastic modulus of CNF-PP bionanocomposites shows small improvement when the adhesion between hydrophobic and hydrophilic components is facilitated by a MAH coupling agent. The results demonstrate how fully-atomistic MD simulations can be systematically used to evaluate the elastic properties of CNF-PP bionanocomposites and to make predictions that are in agreement with experiments.
The Effects of Lengths of Flavin Surfactant N-10-Alkyl Side Chains on Promoting Dispersion of a High-Purity and Diameter-Selective Single-Walled Nanotube
Authors: Park Minsuk , Hwang Seongjoo , Ju Sang-Yong
Published: September 2022

Flavin with defined helical self-assembly helps to understand chemical designs for obtaining high-purity semiconducting (s)-single-walled carbon nanotubes (SWNT) in a diameter (dt)-selective manner for high-end applications. In this study, flavins containing 8, 12, 16, and 20 n-alkyl chains were synthesized, and their single/tandem effects on dt-selective s-SWNT dispersibility were investigated at isomolarity. Flavins with n-dodecyl and longer chain lengths (FC12, FC16, and FC20) act as good surfactants for stable SWNT dispersions whereas n-octyl flavin (FC8) exhibits poor dispersibility owing to the lack of SWNT buoyancy. When used with small-dt SWNT, FC8 displays chirality-selective SWNT dispersion. This behavior, along with various flavin helical motifs, prompts the development of criteria for ‘side chain length (lS)’ required for stable and dt-selective SWNT dispersion, which also explains lS-dependent dt-enrichment behavior. Moreover, SWNT dispersions with flavins with dodecyl and longer lS exhibit increased metallic (m)-SWNT, background absorption-contributing carbonaceous impurities (CIs) and preferential selectivity of s-SWNT with slightly larger dt. The increased CIs that affect the SWNT quantum yield were attributed to a solubility parameter. Furthermore, the effects of flavin lS, sonication bath temperature, centrifugal speed, and surfactant concentration on SWNT purity and s-/m-SWNT ratio were investigated. A tandem FC8/FC12 provides fine-tuning of dt-selective SWNT dispersion, wherein the FC8 ratio governs the tendency towards smaller dt. Kinetic and thermodynamic assemblies of tandem flavins result in different sorting behaviors in which wide dt-tunability was demonstrated using kinetic assembly. This study highlights the importance of appropriate side chain length and other extrinsic parameters to obtain dt-selective or high-purity s-SWNT.
A Novel p-Type ZnCoxOy Thin Film Grown by Atomic Layer Deposition
Authors: Li Leyi , Wan Zhixin , Wen Quan , Lv Zesheng , Xi Bin
Published: September 2022

Reported herein is the atomic layer deposition (ALD) of novel ternary ZnCoxOy films possessing p-type semiconducting behavior. The preparation comprises of optimized ZnO and Co3O4 deposition in sub-cycles using the commercially available precursors cyclopentadienylcobalt dicarbonyl (CpCo(CO)2), diethylzinc (DEZ) and ozone (O3). A systematic exploration of the film’s microstructure, crystallinity, optical properties and electrical properties was conducted and revealed an association with Zn/Co stoichiometry. The noteworthy results include the following: (1) by adjusting the sub-cycle of ZnO/ Co3O4 to 1/10, a spinel structured ZnCoxOy film was grown at 150 °C, with it exhibiting a smooth surface, good crystallinity and high purity; (2) the material transmittance and bandgap decreased as the Co element concentration increased; (3) the ZnCoxOy film is more stable than its p-type analog Co3O4 film; and (4) upon p-n diode fabrication, the ZnCoxOy film demonstrated good rectification behaviors as well as very low and stable reverse leakage in forward and reverse-biased voltages, respectively. Its application in thin film transistors and flexible or transparent semiconductor devices is highly suggested.
Structure and Surface Relaxation of CeO2 Nanoparticles Unveiled by Combining Real and Reciprocal Space Total Scattering Analysis
Authors: Scavini Marco , Bertolotti Federica , Mlloja Jonadri , Umbri Filippo , Bosc Anna , Cappelli Serena , Checchia Stefano , Oliva Cesare , Fumagalli Patrizia , Ceresoli Davide , Longhi Mariangela , Guagliardi Antonietta , Coduri Mauro
Published: September 2022

We present a combined real and reciprocal space structural and microstructural characterization of CeO2 nanoparticles (NPs) exhibiting different crystallite sizes; ~3 nm CeO2 NPs were produced by an inverse micellae wet synthetic path and then annealed at different temperatures. X-ray total scattering data were analyzed by combining real-space-based Pair Distribution Function analysis and the reciprocal-space-based Debye Scattering Equation method with atomistic models. Subtle atomic-scale relaxations occur at the nanocrystal surface. The structural analysis was corroborated by ab initio DFT and force field calculations; micro-Raman and electron spin resonance added important insights to the NPs’ defective structure. The combination of the above techniques suggests a core-shell like structure of ultrasmall NPs. These exhibit an expanded outer shell having a defective fluorite structure, while the inner shell is similar to the bulk structure. The presence of partially reduced O2−δ species testifies to the high surface activity of the NPs. On increasing the annealing temperature, the particle dimensions increase, limiting disorder as a consequence of the progressive surface-to-volume ratio reduction.
In Silico Identification and Characterization of circRNAs as Potential Virulence-Related miRNA/siRNA Sponges from Entamoeba histolytica and Encystment-Related circRNAs from Entamoeba invadens
Authors: López-Luis Mario Ángel , Padrón-Manrique Cristian Julio César , García-Lerena Jesús Alberto , Lozano-Amado Daniela , Hernández-Rivas Rosaura , Saucedo-Cárdenas Odila , Méndez-Tenorio Alfonso , Valdés Jesús
Published: September 2022

Ubiquitous eukaryotic non-coding circular RNAs regulate transcription and translation. We have reported full-length intronic circular RNAs (flicRNAs) in Entamoeba histolytica with esterified 3′ss and 5′ss. Their 5′ss GU-rich elements are essential for their biogenesis and their suggested role in transcription regulation. Here, we explored whether exonic, exonic-intronic, and intergenic circular RNAs are also part of the E. histolytica and E. invadens ncRNA RNAome and investigated their possible functions. Available RNA-Seq libraries were analyzed with the CIRI-full software in search of circular exonic RNAs (circRNAs). The robustness of the analyses was validated using synthetic decoy sequences with bona fide back splice junctions. Differentially expressed (DE) circRNAs, between the virulent HM1:IMSS and the nonvirulent Rahman E. histolytica strains, were identified, and their miRNA sponging potential was analyzed using the intaRNA software. Respectively, 188 and 605 reverse overlapped circRNAs from E. invadens and E. histolytica were identified. The sequence composition of the circRNAs was mostly exonic although different to human circRNAs in other attributes. 416 circRNAs from E. histolytica were virulent-specific and 267 were nonvirulent-specific. Out of the common circRNAs, 32 were DE between strains. Finally, we predicted that 8 of the DE circRNAs could function as sponges of the bioinformatically reported miRNAs in E. histolytica, whose functions are still unknown. Our results extend the E. histolytica RNAome and allow us to devise a hypothesis to test circRNAs/miRNAs/siRNAs interactions in determining the virulent/nonvirulent phenotypes and to explore other regulatory mechanisms during amoebic encystment.
Development and Validation of the Vietnamese Children’s Short Dietary Questionnaire to Evaluate Food Groups Intakes and Dietary Practices among 9–11-Year-Olds Children in Urban Vietnam
Authors: Mai Thi My Thien , Tran Quoc Cuong , Nambiar Smita , Pols Jolieke C. Van der , Gallegos Danielle
Published: September 2022

This study aims to develop and assess the reproducibility and validity of the Vietnamese Children’s Short Dietary Questionnaire (VCSDQ) in evaluating food groups intakes and dietary practices among school-aged children 9–11 years old in urban Vietnam. A 26-item questionnaire covering frequency intakes of five core food groups, five non-core food groups, five dietary practices over a week, and daily intakes of fruits, vegetables, and water was developed. Children (n = 144) from four primary schools in four areas of Ho Chi Minh City, Vietnam completed the VCSDQ twice, as well as three consecutive 24 h recalls over a week. Intra-class correlation, Spearman correlation, weighted kappa, cross-classification, and Bland–Altman plots were used to evaluate the reproducibility and validity. The direct validity of food groups from VCSDQ against the 24 h recalls was examined using Wilcoxon-test for trend. The VCSDQ had good reproducibility in 12 out of 15 group items; the ICC ranged from 0.33 (grains) to 0.84 (eating while watching screens). This VCSDQ had low relative validity, two items (instant noodles, eating while watching screens) had a moderate to good agreement (k = 0.43, k = 0.84). There was good direct validity in three core-food groups (fruits, vegetables, dairy) and three non-core food groups (sweetened beverages, instant noodles, processed meat). In addition, the VCSDQ can also be used to classify daily intakes of fruits and vegetables from low to high.
Potential Modulation of Inflammation by Probiotic and Omega-3 Supplementation in Elderly with Chronic Low-Grade Inflammation—A Randomized, Placebo-Controlled Trial
Authors: Tingö Lina , Hutchinson Ashley N. , Bergh Cecilia , Stiefvatter Lena , Schweinlin Anna , Jensen Morten G. , Krüger Kirsten , Bischoff Stephan C. , Brummer Robert J.
Published: September 2022

Probiotic and omega-3 supplements have been shown to reduce inflammation, and dual supplementation may have synergistic health effects. We investigated if the novel combination of a multi-strain probiotic (containing B. lactis Bi-07, L. paracasei Lpc-37, L. acidophilus NCFM, and B. lactis Bl-04) alongside omega-3 supplements reduces low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) in elderly participants in a proof-of-concept, randomized, placebo-controlled, parallel study (NCT04126330). In this case, 76 community-dwelling elderly participants (median: 71.0 years; IQR: 68.0–73.8) underwent an intervention with the dual supplement (n = 37) or placebo (n = 39) for eight weeks. In addition to hs-CRP, cytokine levels and intestinal permeability were also assessed at baseline and after the eight-week intervention. No significant difference was seen for hs-CRP between the dual supplement group and placebo. However, interestingly, supplementation did result in significant increases in the level of the anti-inflammatory marker IL-10. In addition, dual supplementation increased levels of valeric acid, further suggesting the potential of the supplements in reducing inflammation and conferring health benefits. Together, the results suggest that probiotic and omega-3 dual supplementation exerts modest effects on inflammation and may have potential use as a non-pharmacological treatment for low-grade inflammation in the elderly.
Can Nutrition Play a Role in Ameliorating Digital Eye Strain?
Authors: Lem Drake W. , Gierhart Dennis L. , Davey Pinakin Gunvant
Published: September 2022

Digital eye strain is a complex, multifactorial condition that can be caused by excessive screen time exposure to various electronic devices such as smartphones, tablets, e-readers, and computers. Current literature suggests oxidative damage concomitant with a chronic pro-inflammatory state represent significant etiopathogenic mechanisms. The present review aims to discuss the potential dietary role for micronutrients with nutraceutical properties to ameliorate various ocular and vision-related symptoms associated with digital eye strain. For ocular surface dysfunction, enhanced anti-inflammatory benefits with omega-3 polyunsaturated fatty acids have been well documented for treatment of dry eye disease. The anti-oxidative and immunosuppressive properties of anthocyanin phytochemicals may also confer protective effects against visually induced cognitive stress and digital asthenopia. Meanwhile, nutraceutical strategies involving xanthophyll macular carotenoids demonstrate enhanced cognitive functioning and overall visual performance that aids digital eye strain. Collectively, preliminary findings seem to offer a strong line of evidence to substantiate the need for additional randomized controlled trials aimed at treating digital eye strain with adjunctive nutraceutical strategies. Further RCT and comparisons on commercially available nutritional supplements are needed to quantify the clinical benefits.
Food Costs of Children and Adolescents Consuming Vegetarian, Vegan or Omnivore Diets: Results of the Cross-Sectional VeChi Youth Study
Authors: Hohoff Eva , Zahn Helena , Weder Stine , Fischer Morwenna , Längler Alfred , Michalsen Andreas , Keller Markus , Alexy Ute
Published: September 2022

The aim was to analyse the total food costs and the impact of food groups on total food costs among vegetarian, vegan and omnivore children and adolescents in Germany. Based on three-day weighed dietary records of 6–18-year-old children and adolescents of the VeChi Youth Study, the total daily food costs and food group costs (both EUR/day, EUR/1000 kcal) of a vegetarian (n = 145 records), vegan (n = 110) and omnivore (n = 135) diet were calculated. Minimum retail prices of 1000 empirically selected foods reported in the dietary records were linked to individual food intakes. The group differences were analysed using ANCOVA or Kruskal-Wallis tests. Vegans had the highest energy adjusted total food costs at 2.98 EUR/1000 kcal, vegetarians the lowest at 2.52 EUR/1000 kcal. Omnivores also had significantly higher costs than vegetarians with 2.83 EUR/1000 kcal/1000 kcal (p = 0.01), but the total costs did not differ significantly between omnivores and vegans (EUR/d and EUR/1000 kcal). Compared to vegetarians, vegans had significantly higher expenditures (EUR/day) on fruit (p = 0.0003), vegetables (p = 0.006), dairy alternatives (p = 0.0003) and legumes/nuts/seeds (p = 0.0003). Expenditure on starchy foods was significantly higher in the vegetarian or vegan than in the omnivore diet (p = 0.0003). Omnivores spent a quarter of their total food costs on animal source foods (25%), which is equivalent to the sum of food costs for legumes/nuts/seeds, dairy alternatives and meat alternatives in vegans and additionally dairy in vegetarians. The VeChi Youth Study indicated that financial constraints are not necessarily a barrier to switching to a more plant-based diet.
Higher Serum 25-Hydroxyvitamin D Is Associated with Lower All-Cause and Cardiovascular Mortality among US Adults with Nonalcoholic Fatty Liver Disease
Authors: Chen Yuxiong , Feng Siqin , Chang Zhen’ge , Zhao Yakun , Liu Yanbo , Fu Jia , Liu Yijie , Tang Siqi , Han Yitao , Zhang Shuyang , Fan Zhongjie
Published: September 2022

Aims: We aimed to assess the association between serum 25-hydroxyvitamin D (25(OH)D) levels with all-cause and cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). Methods: We performed a retrospective cohort study based on the US National Health and Nutrition Examination Survey 2001–2016 on adults aged ≥20 years. NAFLD was determined as a US Fatty Liver Index score ≥ 30 in the absence of other liver conditions. Weighted Cox proportional hazards regression models were applied to explore the relationship between serum 25(OH)D levels and mortality. Results: 898 all-cause deaths and 305 cardiovascular deaths were recorded over a median follow-up of 8.7 years. Compared with those in the severe deficiency group (below 25.0 nmol/L), the fully adjusted HRs and 95% CIs of NAFLD patients with sufficient serum 25(OH)D concentrations (≥75.0 nmol/L) were 0.36 (0.22, 0.60) for all-cause mortality and 0.14 (0.07, 0.29) for cardiovascular mortality. Each one-unit increase in the natural log-transformed serum 25(OH)D concentration was related to a 41% lower risk for all-cause deaths (HR = 0.59, 95% CI: 0.46, 0.77) and a 65% lower risk for cardiovascular deaths (HR = 0.35, 95% CI: 0.22, 0.58). Conclusions: Among NAFLD patients, increased serum 25(OH)D levels were independently associated with reduced risk for all-cause and cardiovascular deaths.
The Role of Infant Formulas in the Primary Prevention of Allergies in Non-Breastfed Infants at Risk of Developing Allergies—Recommendations from a Multidisciplinary Group of Experts
Authors: Dias Jorge Amil , Santos Edmundo , Asseiceira Inês , Jacob Sylvia , Koninckx Carmen Ribes
Published: September 2022

The worldwide incidence of allergic diseases has been continuously increasing, and up to one in every five people are currently affected by these medical conditions. Although seldom fatal, allergies have a profound impact on children’s growth, development, and quality of life, besides being associated with heavy healthcare costs and resource utilisation. In this context, a group of experts in nutrition, paediatric gastroenterology, allergology, and neonatology joined forces to discuss the role of infant formulas in the primary prevention of allergies in infants for whom breastfeeding is not an option and who are at risk of developing allergies. The topics discussed included the assessment of risk, the impact of the microbiota on the modulation of immune tolerance, and the added value of certain formula characteristics, namely, protein integrity (hydrolysed protein vs. intact protein) and the addition of prebiotics, probiotics, or synbiotics. This article describes the latest evidence on each of the above-mentioned points, as well as a number of recommendations made by the experts to guide counselling of parents in the choice of a formula for infants at risk of allergy. Overall, the experts highlighted family history and dysbiosis-promoting factors (namely, caesarean delivery and antibiotic use) as two of the most important risk factors for allergy development. Moreover, in line with international guidelines, the panel advocated that intact protein formula should be offered to all bottle-fed healthy infants, irrespective of their allergic risk (with the exception of short-term bottle feeding of otherwise breastfed babies in their first week of life, for whom a hydrolysed formula may be advisable). Finally, the experts agreed that the use of prebiotic-, probiotic-, or synbiotic-enriched formulas should be considered in infants at risk of developing allergies.
The Safety and Efficacy of Citrus aurantium (Bitter Orange) Extracts and p-Synephrine: A Systematic Review and Meta-Analysis
Authors: Koncz Dorottya , Tóth Barbara , Bahar Muh. Akbar , Roza Orsolya , Csupor Dezső
Published: September 2022

Synephrine has been used to promote weight loss; however, its safety and efficacy have not been fully established. The goals of our study were to give an overview of the safety and efficacy of p-synephrine, to systematically evaluate its efficacy regarding weight loss and to assess its safety, focusing on its cardiovascular side effects in a meta-analysis. PubMed, the Cochrane Library, Web of Science and Embase were searched for relevant studies. Only placebo-controlled, human clinical trials with synephrine intervention were included in the meta-analysis. The meta-analysis was reported according to the PRISMA guidelines using the PICOS format and taking into account the CONSORT recommendations. Altogether, 18 articles were included in the meta-analysis. Both systolic and diastolic blood pressure (DBP) increased significantly after prolonged use (6.37 mmHg, 95% CI: 1.02–11.72, p = 0.02 and 4.33 mmHg, 95% CI: 0.48–8.18, p = 0.03, respectively). The weight loss in the synephrine group was non-significant after prolonged treatment, and it did not influence body composition parameters. Based on the analyzed clinical studies, synephrine tends to raise blood pressure and heart rate, and there is no evidence that synephrine can facilitate weight loss. Further studies are needed to confirm evidence of its safety and efficacy.
Ketoanalogues Supplemental Low Protein Diet Safely Decreases Short-Term Risk of Dialysis among CKD Stage 4 Patients
Authors: Yen Chieh-Li , Fan Pei-Chun , Chen Jia-Jin , Kuo George , Hsiao Ching-Chung , Chen Chao-Yu , Tu Yi-Ran , Hsu Hsiang-Hao , Chen Yung-Chang , Chang Chih-Hsiang
Published: September 2022

Background: Rigid dietary controls and pill burden make a very-low protein (0.3–0.4 g/kg body weight per day), vegetarian diet supplemented with ketoanalogues of amino acids (sVLPD) hard to follow in the long-term. This study aimed to evaluate whether a ketoanalogue supplemental low-protein diet (sLPD) (0.6 g/kg body weight per day) could also reduce the risks of dialysis among CKD stage 4 patients. Methods: Patients aged >20 years with a diagnosis of stage 4 CKD who subsequently received ketosteril treatment, which is the most commonly used ketoanalogue of essential amino acids, between 2003 and 2018 were identified from the Chang Gung Research Database (CGRD). Then, these individuals were divided into two groups according to the continuation of ketosteril for more than three months or not. The primary outcome was ESKD requiring maintenance dialysis. Results: With one-year follow-up, the continuation group (n = 303) exhibited a significantly lower incidence of new-onset end-stage kidney disease (ESKD) requiring maintenance dialysis (6.8% vs. 10.4%, hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.41–0.94) in comparison to the discontinuation group (n = 238). Conclusions: This study demonstrated that initiating sLPDs since CKD stage 4 may additionally reduce the short-term risks of commencing dialysis without increasing CV events, infections, or mortality.
Eating Choices—The Roles of Motivation and Health Literacy: A Cross-Sectional Study
Authors: Zwierczyk Urszula , Sowada Christoph , Duplaga Mariusz
Published: September 2022

Food choices are determined by intrinsic and extrinsic product characteristics, biological and physiological features, psychological factors, and situational and socio-cultural factors. Self-determination theory offers the explanation of health behavior change identifying motivations located along a continuum of autonomy. Another approach to the motivations guiding health behaviors, including food choices, relies on distinguishing thematic categories. Health motivations seem to be an obvious determinant of health behaviors, but final decisions regarding health are also the effect of other types of motivations such as economic, cultural, or emotional. The role of marketing pressure in modern society is perceived to be an important source of motivation for purchasing food and other products. The Motivation–Opportunity–Ability (MOA) framework was initially proposed in order to explain the processing of brand information from advertisements and was later expanded to other areas, including health and nutritional behaviors. The aim of this study was the analysis of determinants of food choices. We have developed a common regression model including six categories of motivations addressed by the Eating Motivations Scale and three health literacy types corresponding with element of ability from the MOA framework, adjusted for socio-demographic factors, health status, and the use of the Internet and TV. The analysis was performed on data from a computer-assisted web-based interviewing (CAWI) survey among 2008 adult Internet users completed in May 2022. The uni- and multivariate linear regression models were developed with the Index of Unhealthy Food Choices (IUFC), calculated based on the responses to items asking about the frequency of the consumption of twelve food categories. Univariate modeling revealed that IUFC is significantly associated with health, food, and e-health literacies and with five out of six eating motivations. However, the multivariate regression model yielded significant associations only for eating motivations but not for the three literacy scores. Health motivation was negatively associated with IUFC (B, standard error (SE): 0.83, 0.07; 95% confidence interval (95% CI): 0.98–0.69), but positively with emotional (B, SE: 0.22, 0.04; 95% CI: 0.14–0.3), economic (B, SE: 0.41, 0.08; 95% CI: 0.25–0.56), and marketing (B, SE: 0.62, 0.08; 95% CI: 0.47–0.78) motivations. Our findings suggest that motivations guiding food choices may prevail over the element of ‘ability’ distinguished in the frameworks and models that explain people’s behaviors, including behaviors relating to health. Thus, it is essential to emphasize development of appropriate motivations and not only to provide knowledge and skills. Furthermore, one should also remember motivations other than health motivations when searching for the determinants of health behaviors.
Heart Rate Variability and Laboratory-Based Loss-of-Control Eating in Children and Adolescents
Authors: Parker Megan N. , Faulkner Loie M. , Shank Lisa M. , Schvey Natasha A. , Loch Lucy K. , Haynes Hannah E. , Bloomer Bess F. , Moursi Nasreen A. , Fatima Syeda , Te-Vazquez Jennifer A. , Brady Sheila M. , Yang Shanna B. , Turner Sara A. , Tanofsky-Kraff Marian , Yanovski Jack A.
Published: September 2022

Among youth, greater heart rate (HR) and lesser HR variability (HRV) are precursors to loss-of-control (LOC) eating episodes in the natural environment. However, there are limited data examining whether pre-meal HR and HRV are associated with greater LOC-eating in the laboratory setting. We therefore examined temporal relationships between pre-meal HR, frequency- and time-based metrics of pre-meal HRV, perceived LOC-eating, and energy intake during a meal designed to simulate a LOC-eating episode. Among 209 participants (54.5% female, 12.58 ± 2.72 years, 0.52 ± 1.02 BMIz), 19 reported LOC-eating in the prior month. Perceived LOC-eating during the laboratory meal was not significantly linked to pre-meal HR (p = 0.37), but was positively related to pre-meal HRV (ps = 0.02–0.04). This finding was driven by youth with recent LOC-eating, as these associations were not significant when analyses were run only among participants without recent reported LOC-eating (p = 0.15–0.99). Pre-meal HR and HRV were not significantly related to total energy intake (ps = 0.27–0.81). Additional research is required to determine whether early-stage pediatric LOC-eating is preceded by a healthy pre-meal stress response. Longitudinal studies could help clarify whether this pattern becomes less functional over time among youth who develop recurrent LOC-eating episodes.
Vulnerability in Children with Celiac Disease: A Scoping Review Protocol
Authors: Macedo Lúcia , Catarino Marta , Festas Constança , Alves Paulo
Published: September 2022

(1) Background: The scientific literature reports that children with celiac disease (CD) are more susceptible to developing physical, psychological and social problems, conditioning their healthy childhood development. Despite this scientific evidence, the knowledge about determinants of vulnerability for the development of such problems is not consistent. In order to search the literature, a scoping review was conducted to analyse and map the evidence on the sociopsychosomatic vulnerability of children with CD and identify the gaps in this topic. (2) Methods: The methodology proposed by the Joanna Briggs Institute will be adopted and aims to identify studies that meet pre-defined eligibility criteria. The survey will include a range of relevant electronic databases as well as grey literature using related terms such as vulnerability, child and celiac disease. (3) Results: This review will consider any type of quantitative, qualitative and mixed studies and systematic reviews, focusing on dimensions of vulnerability in children with CD. The process of selection of studies, data extraction and analysis will be developed by two independent researchers. A third and fourth researcher will be involved in the study when there is no consensus between the previous researchers, as well as for resolving issues regarding the methodological process. (4) Conclusions: Identifying the determinants of vulnerability in children with CD will help nurses to understand the impact on their childhood development and trace possible gaps. This research is registered on the platform Open Science Framework (OSF).
Strandings in St Vincent Gulf Bioregion, South Australia: 12-Year Study Monitors Biology and Pathology of Cetaceans
Authors: Tomo Ikuko , Kemper Catherine M.
Published: September 2022

The semi-enclosed environment of the St Vincent Gulf Bioregion and its fauna are impacted by many human activities. Long-term monitoring of cetaceans is vital. Records of collected specimens (173) and those not examined by the South Australian Museum (98 non-specimens) from 2009–2020 were analyzed. Necropsies were carried out on most carcasses using gross, histopathological, and diagnostic assessment of pathogens, organs, and skin lesions. The relative age and circumstance of death were assigned. Baleen whales (five species) and odontocetes (eight species) were studied. Indo-Pacific bottlenose dolphins (Tursiops aduncus) and common dolphins (Delphinus delphis) were frequently recorded and analyzed in detail. Anthropogenic cases were prevalent (21%). Many dolphins (62%) were immature males. Disease (73%) was the most frequently recorded circumstance of death. The most common pathological change was inflammatory disease, including infectious pneumonia. In Indo-Pacific bottlenose dolphins, infectious disease was more prevalent in the greater St Vincent Gulf Bioregion than in the Adelaide Dolphin Sanctuary. Microbe testing confirmed 32 species of bacteria, 2 fungi, and 1 virus. Nematodes and trematodes were recorded throughout the study, sometimes in association with microbes. Toxoplasma gondii was observed in an Indo-Pacific bottlenose dolphin. Severe traumatic injury was recorded in many dolphins, including anthropogenic cases. A tumor (leiomyoma) was described from a single common dolphin. This study provides an important baseline for the future monitoring of emerging infectious and chronic diseases, and anthropogenic threats in the region.
Tablets Made from Paper—An Industrially Feasible Approach
Authors: Abdelkader Ayat , Moos Christoph , Pelloux Adrien , Pfeiffer Marcus , Alter Christian , Kolling Stefan , Keck Cornelia M.
Published: September 2022

Many orally administrated drugs exhibit poor bioavailability due to their limited solubility. The smartFilm technology is an innovative approach to improve the drug aqueous solubility, where the drug is embedded within the matrix of cellulose-based paper in an amorphous state, hence increasing its solubility. Despite its proven effectiveness, smartFilms, i.e., pieces of paper, exhibit limited flowability and are not easy to swallow, and thus oral administration is not convenient. In addition, there is a lack of knowledge of their mechanical behavior under compression. This study aimed to transform unloaded smartFilms, i.e., paper, into a flowable physical form and investigated its mechanical behavior when compressed. Granules made of paper were prepared via wet granulation and were compressed into tablets. The influence of using different amounts and forms of sucrose, as a binder, on the pharmaceutical properties of the produced granules and tablets was studied and the most suitable composition was identified by using instrumented die experiments. For this, the Poisson’s ratio and Young’s modulus were determined for different compaction force levels and the deformation behavior was estimated with the Heckel mathematical model. All granule batches showed good flowability with angle of repose values between 25–35°. Granule batches with ≤30% dry sucrose content produced tablets that fulfilled the European Pharmacopeia requirements, and the compaction behavior of the granules was found to be comparable to the behavior of classical binders and compression enhancers. Paper can be transferred into granules. These granules can be used as suitable intermediate products for the production of tablets made of paper in large, industrial scale.
Calcitonin Gene-Related Peptide (CGRP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Migraine Pathogenesis
Authors: Christensen Casper Emil , Ashina Messoud , Amin Faisal Mohammad
Published: September 2022

Migraine is a prevalent and debilitating neurologic disorder. Advancements in understanding the underlying pathophysiological mechanisms are spearheading the effort to introduce disease-specific treatment options. In recent years this effort has largely focused on alteration of endogenous neuropeptide signaling, namely the peptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Human studies into the pathophysiological underpinnings of CGRP and PACAP in migraine are manifold and here we review the works investigating these neuropeptides in patients suffering from migraine in order to elucidate the background for developing new treatment options for this vastly disabling disorder.
Antimicrobial Quantitative Relationship and Mechanism of Plant Flavonoids to Gram-Positive Bacteria
Authors: Yuan Ganjun , Xia Xuexue , Guan Yingying , Yi Houqin , Lai Shan , Sun Yifei , Cao Seng
Published: September 2022

Antimicrobial resistance (AMR) poses a serious threat to human health, and new antimicrobial agents are desperately needed. Plant flavonoids are increasingly being paid attention to for their antibacterial activities, for the enhancing of the antibacterial activity of antimicrobials, and for the reversing of AMR. To obtain more scientific and reliable equations, another two regression equations, between the minimum inhibitory concentration (MIC) (y) and the lipophilicity parameter ACD/LogP or LogD7.40 (x), were established once again, based on the reported data. Using statistical methods, the best one of the four regression equations, including the two previously reported, with regard to the antimicrobial quantitative relationship of plant flavonoids to Gram-positive bacteria, is y = −0.1285 x6 + 0.7944 x5 + 51.785 x4 − 947.64 x3 + 6638.7 x2 − 21,273 x + 26,087; here, x is the LogP value. From this equation, the MICs of most plant flavonoids to Gram-positive bacteria can be calculated, and the minimum MIC was predicted as approximately 0.9644 μM and was probably from 0.24 to 0.96 μM. This more reliable equation further proved that the lipophilicity is a key factor of plant flavonoids against Gram-positive bacteria; this was further confirmed by the more intuitive evidence subsequently provided. Based on the antibacterial mechanism proposed in our previous work, these also confirmed the antibacterial mechanism: the cell membrane is the major site of plant flavonoids acting on the Gram-positive bacteria, and this involves the damage of the phospholipid bilayers. The above will greatly accelerate the discovery and application of plant flavonoids with remarkable antibacterial activity and the thorough research on their antimicrobial mechanism.
Glu-Urea-Lys Scaffold Functionalized Superparamagnetic Iron Oxide Nanoparticles Targeting PSMA for In Vivo Molecular MRI of Prostate Cancer
Authors: Zhou Wei , Huang Jiandong , Xiao Qingwei , Hu Shunmin , Li Shijia , Zheng Jie , Du Zhiyun , Peng Jiangling , Chen Huixiong
Published: September 2022

The prostate specific membrane antigen (PSMA), extensively overexpressed on prostate cancer (PCa) cell surface, has been validated as a diagnostic biomarker for PCa. However, insufficient attention has been paid to the development of PSMA-specific probes loaded with small chemical molecules for the in vivo molecular imaging of PCa. In this study, we innovatively labelled superparamagnetic iron oxide nanoparticles with a PSMA-targeting Glu-Urea-Lys scaffold. An optimized synthetic route was developed to offer a physiochemically stable probe. The probe demonstrated high binding affinity (0.38 ± 0.08 μg(Fe)/mL) and binding specificity to PSMA expressed on prostate cancer cell surface in vitro. In a xenograft PCa mouse model, significant negative contrast of the implanted prostate cancer xenograft could be specifically observed by MRI 6 h after tail vein injection of the tracer (Fe, 20 mg/kg), exhibiting its potential to exclusively enhance magnetic resonance detection of PCa.
Development of a Luliconazole Nanoemulsion as a Prospective Ophthalmic Delivery System for the Treatment of Fungal Keratitis: In Vitro and In Vivo Evaluation
Authors: Yang Jingjing , Liang Zhen , Lu Ping , Song Fei , Zhang Zhen , Zhou Tianyang , Li Jingguo , Zhang Junjie
Published: September 2022

Luliconazole (LCZ), a novel imidazole drug, has broad-spectrum and potential antifungal effects, which makes it a possible cure for fungal keratitis; nevertheless, its medical use in ocular infections is hindered by its poor solubility. The purpose of this study was to design and optimize LCZ nanoemulsion (LCZ-NE) formulations using the central composite design-response surface methodology, and to investigate its potential in improving bioavailability following ocular topical administration. The LCZ-NE formulation was composed of Capryol 90, ethoxylated hydrogenated castor oil, Transcutol® P and water. The shape of LCZ-NE was spherical and uniform, with a droplet size of 18.43 ± 0.05 nm and a low polydispersity index (0.070 ± 0.008). The results of an in vitro release of LCZ study demonstrated that the LCZ-NE released more drug than an LCZ suspension (LCZ-Susp). Increases in the inhibition zone indicated that the in vitro antifungal activity of the LCZ-NE was significantly improved. An ocular irritation evaluation in rabbits showed that the LCZ-NE had a good tolerance in rabbit eyes. Ocular pharmacokinetics analysis revealed improved bioavailability in whole eye tissues that were treated with LCZ-NE, compared with those treated with LCZ-Susp. In conclusion, the optimized LCZ-NE formulation exhibited excellent physicochemical properties, good tolerance, enhanced antifungal activity and bioavailability in eyes. This formulation would be safe, and shows promise in effectively treating ocular fungal infections.
Evaluation of Newly Designed and Traditional Punches in Manufacturing of Scored ODTs
Authors: Palugan Luca , Moutaharrik Saliha , Maroni Alessandra , Foppoli Anastasia Anna , Melocchi Alice , Vecchio Carlo , Gazzaniga Andrea , Cerea Matteo
Published: September 2022

To overcome difficulties in splitting, uneven breaking and inconsistent dosing frequently reported with scored tablets, a novel punch was proposed for the manufacturing of easy breakable tablets (EBTs). In this work, the performance of the EBT punch was investigated vs. a ridged one for traditional breakable tablets (TBTs) using a furosemide powder formulation for orally disintegrating tablets (ODTs). A Face Centered Central Composite Design was applied to investigate the influence of punch type, compaction force, tablet weight and press rotation speed on the mechanical properties of ODTs, their behavior in aqueous fluids and aptitude for splitting. Mass uniformity and adequate crushing strength, friability, water uptake, disintegration and wetting times were obtained from both TBTs and EBTs. Interestingly, more favorable splitting behavior was shown by tablets manufactured by the novel punch, in view of lower mass loss and portion mass variability after breaking. The ease of breaking, accuracy of subdivision and mass loss of ODTs were also evaluated by a volunteer (n = 20) panel test. Less difficulty was found in splitting EBTs than TBTs (p < 0.05), and a larger number of tablets were properly broken into four parts. Thus, this study proved the usefulness of the EBT punch in overcoming drawbacks associated with divisible tablets.
Platinum(IV) Complexes of the 1,3,5-Triamino Analogue of the Biomolecule Cis-Inositol Designed as Innovative Antineoplastic Drug Candidates
Authors: Velcheva Vyara , Hegetschweiler Kaspar , Momekov Georgi , Ivanova Stefka , Ugrinov Angel , Morgenstern Bernd , Gencheva Galina
Published: September 2022

Metal complexes occupy a special place in the field of treatment and diagnostics. Their main advantages stem from the possibility of fine-tuning their thermodynamic properties and kinetic behavior in the biological milieu by applying different approaches such as properly constructed inner coordination sphere, appropriate choice of ligands, metal oxidation state, redox potential, etc., which are specific to these compounds. Here we discuss the design and synthesis of two octahedral cationic Pt(IV) complexes of the tridentate ligand all-cis-2,4,6-triaminocyclohexane-1,3,5-triol (taci) with composition, fac-[Pt(taci)I3]+, 1 and bis-[Pt(taci)2]4+, 2 as well as the potential for their application as antineoplastic agents. The complexes have been isolated in a solid state as: fac-[Pt(taci)I3]I·3H2O (1A), fac-[Pt(taci)I3]I (1B), fac-[Pt(taci)I3]I·2DMF (1C), bis-[Pt(taci)2](CO3)2·6H2O (2A) by changing the acidity of the reaction systems, the molar ratios of the reagents and the counterions, and by re-crystallization. The ligand taci is coordinated through the NH2-groups, each molecule occupying three coordination places in the inner coordination sphere of Pt(IV). Monitoring of the hydrolysis processes of 1A and 2A at different acidity showed that while 2A remained stable over the study period, the I−-ions in 1A were successively substituted, with the main product under physiologically mimetic conditions being fac,cis-[Pt(taci)I(OH)2]+ (h2). The antiproliferative tests involved eight cancer cell models, among which chemosensitive (derived from leukemias and solid tumors) and chemoresistant human Acute myeloid leukemia lines (HL-60/Dox, HL-60/CDDP), as well as the non-malignant kidney’ cells HEK-293T showed that the complexes 1A and 2A are characterized by a fundamentally different profile of chemosensitivity and spectrum of cytotoxic activity compared to cisplatin. The new Pt(IV) complexes were shown to be more effective in selectively inhibiting the proliferation of human malignant cells compared to cisplatin. Remarkable activity was recorded for 1A, which showed an effect (IC50 = 8.9 ± 2.4) at more than 16-fold lower concentration than cisplatin (IC50 = 144.4 ± 9.8) against the resistant cell line HL-60/CDDP. In parallel, 1A exhibited virtually the same cytotoxic effect against the parental HL-60 cells (IC50 = 9.0 ± 1.2), where cisplatin displays comparable chemosensitivity (IC50 = 8.3 ± 0.8). The determined resistance indices (RI~1) show unequivocally that the resistant lines are sensitive to both compounds tested; therefore, they are capable of overcoming the mechanisms of cisplatin resistance. The structural features of these compounds and their promising pharmacological properties justify their inclusion in the group of “non-classical metal-based antitumor compounds” and are a prerequisite for the admission of alternative mechanisms of action.
Pharmacometric Modeling of the Impact of Azelastine Nasal Spray on SARS-CoV-2 Viral Load and Related Symptoms in COVID-19 Patients
Authors: Dings Christiane , Meiser Peter , Holzer Frank , Flegel Michael , Selzer Dominik , Nagy Eszter , Mösges Ralph , Klussmann Jens Peter , Lehr Thorsten
Published: September 2022

The histamine-1 receptor antagonist azelastine was recently found to impact SARS-CoV-2 viral kinetics in a Phase 2 clinical trial (CARVIN). Thus, we investigated the relationship between intranasal azelastine administrations and viral load, as well as symptom severity in COVID-19 patients and analyzed the impact of covariates using non-linear mixed-effects modeling. For this, we developed a pharmacokinetic (PK) model for the oral and intranasal administration of azelastine. A one-compartment model with parallel absorption after intranasal administration described the PK best, covering both the intranasal and the gastro-intestinal absorption pathways. For virus kinetic and symptoms modeling, viral load and symptom records were gathered from the CARVIN study that included data of 82 COVID-19 patients receiving placebo or intranasal azelastine. The effect of azelastine on viral load was described by a dose–effect model targeting the virus elimination rate. An extension of the model revealed a relationship between COVID-19 symptoms severity and the number of infected cells. The analysis revealed that the intranasal administration of azelastine led to a faster decline in viral load and symptoms severity compared to placebo. Moreover, older patients showed a slower decline in viral load compared to younger patients and male patients experienced higher peak viral loads than females.
ADV6209 for Premedication in Pediatric Anesthesia: A Double-Blinded, Randomized Controlled Trial
Authors: Zadrazil Markus , Marhofer Peter , Schmid Werner , Marhofer Daniela , Opfermann Philipp
Published: September 2022

ADV6209, a new formulation of midazolam with the addition of γ-cyclodextrin for oral use, has recently been licensed as the first pediatric sedative in the European Union. We compared the clinical efficacy of ADV6209 to the standard formulation of midazolam in premedication to reduce anxiety in children before anesthesia induction in a randomized, double-blinded controlled trial. Eighty children (ASA I/II; age: 2–8 years) scheduled for elective surgery were randomized to receive 0.25 mg kg−1 of either conventional midazolam or ADV6209. Assessment tools included the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) as well as scores for oral acceptance of the premedication and facemask acceptance during inhalational anesthesia induction. Mann–Whitney U and Pearson’s chi-square tests were used for comparisons of outcome parameters. The primary outcome parameter of the study (mYPAS-SF anxiety score 30 min after the drug administration) did not reveal any significant intergroup difference between the ADV6209 group and the conventional midazolam group. Both drugs revealed their efficacy in reducing anxiety and in providing adequate sedation. The premedication dose was accepted by all children in the ADV6209 but rejected by 15% in the conventional midazolam group (p = 0.037). Acceptance of facemask placement was not found to differ significantly. No adverse events related to the study medications were noted. ADV6209 was better orally accepted than the conventional midazolam preparation and proved its efficacy in reducing preoperative anxiety. This clinically interesting preparation may alleviate the premedication process of 2−8 year-old children and obviates off-label drug use.