bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile One-Pot Multicomponent Synthesis of Pyrazolo-Thiazole Substituted Pyridines with Potential Anti-Proliferative Activity: Synthesis, In Vitro and In Silico Studies
Authors: El Azab Islam H. , Bakr Rania B. , Elkanzi Nadia A. A.
Published: May 2021

Pyrazolothiazole-substituted pyridine conjugates are an important class of heterocyclic compounds with an extensive variety of potential applications in the medicinal and pharmacological arenas. Therefore, herein, we describe an efficient and facile approach for the synthesis of novel pyrazolo-thiazolo-pyridine conjugate 4, via multicomponent condensation. The latter compound was utilized as a base for the synthesis of two series of 15 novel pyrazolothiazole-based pyridine conjugates (5–16). The newly synthesized compounds were fully characterized using several spectroscopic methods (IR, NMR and MS) and elemental analyses. The anti-proliferative impact of the new synthesized compounds 5–13 and 16 was in vitro appraised towards three human cancer cell lines: human cervix (HeLa), human lung (NCI-H460) and human prostate (PC-3). Our outcomes regarding the anti-proliferative activities disclosed that all the tested compounds exhibited cytotoxic potential towards all the tested cell lines with IC50 = 17.50–61.05 µM, especially the naphthyridine derivative 7, which exhibited the most cytotoxic potential towards the tested cell lines (IC50 = 14.62–17.50 µM) compared with the etoposide (IC50 = 13.34–17.15 µM). Moreover, an in silico docking simulation study was performed on the newly prepared compounds within topoisomerase II (3QX3), to suggest the binding mode of these compounds as anticancer candidates. The in silico docking results indicate that compound 7 was a promising lead anticancer compound which possesses high binding affinity toward topoisomerase II (3QX3) protein.
How to Obtain the Maximum Properties Flexibility of 3D Printed Ketoprofen Tablets Using Only One Drug-Loaded Filament?
Authors: Pyteraf Jolanta , Jamróz Witold , Kurek Mateusz , Szafraniec-Szczęsny Joanna , Kramarczyk Daniel , Jurkiewicz Karolina , Knapik-Kowalczuk Justyna , Tarasiuk Jacek , Wroński Sebastian , Paluch Marian , Jachowicz Renata
Published: May 2021

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.
Synthesis and Modeling of Ezetimibe Analogues
Authors: Salgado Mateo M. , Manchado Alejandro , Nieto Carlos T. , Díez David , Garrido Narciso M.
Published: May 2021

Ezetimibe is a well-known drug that lowers blood cholesterol levels by reducing its absorption in the small intestine when joining to Niemann-Pick C1-like protein (NPC1L1). A ligand-based study on ezetimibe analogues is reported, together with one-hit synthesis, highlighted in the study. A convenient asymmetric synthesis of (2S,3S)-N-α-(R)-methylbenzyl-3-methoxycarbonylethyl-4-methoxyphenyl β-lactam is described starting from Baylis–Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland–Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent inversion of ester and acid functionality paves the way to the lactam core after monodebenzylation and lactam formation. It also shows interesting results when it comes to a pharmacophore study based on ezetimibe as the main ligand in lowering blood cholesterol levels, revealing which substituents on the azetidine-2-one ring are more similar to the ezetimibe skeleton and will more likely bind to NPC1L1 than ezetimibe.
Neuroprotection of N-benzyl Eicosapentaenamide in Neonatal Mice Following Hypoxic–Ischemic Brain Injury
Authors: Jiao Mengya , Dong Qun , Zhang Yiting , Lin Min , Zhou Wan , Liu Tao , Yuan Baohong , Yin Hui
Published: May 2021

Maca (Lepidium meyenii) has emerged as a popular functional plant food because of its medicinal properties and nutritional value. Macamides, as the exclusively active ingredients found in maca, are a unique series of non-polar, long-chain fatty acid N-benzylamides with multiple bioactivities such as antifatigue characteristics and improving reproductive health. In this study, a new kind of macamide, N-benzyl eicosapentaenamide (NB-EPA), was identified from maca. We further explore its potential neuroprotective role in hypoxic–ischemic brain injury. Our findings indicated that treatment with biosynthesized NB-EPA significantly alleviates the size of cerebral infarction and improves neurobehavioral disorders after hypoxic–ischemic brain damage in neonatal mice. NB-EPA inhibited the apoptosis of neuronal cells after ischemic challenge. NB-EPA improved neuronal cell survival and proliferation through the activation of phosphorylated AKT signaling. Of note, the protective property of NB-EPA against ischemic neuronal damage was dependent on suppression of the p53–PUMA pathway. Taken together, these findings suggest that NB-EPA may represent a new neuroprotectant for newborns with hypoxic–ischemic encephalopathy.
A Family of Ethyl N-Salicylideneglycinate Dyes Stabilized by Intramolecular Hydrogen Bonding: Photophysical Properties and Computational Study
Authors: Alkhimova Larisa , Babashkina Maria , Safin Damir
Published: May 2021

In this work we report solvatochromic and luminescent properties of ethyl N-salicylideneglycinate (1), ethyl N-(5-methoxysalicylidene)glycinate (2), ethyl N-(5-bromosalicylidene)glycinate (3), and ethyl N-(5-nitrosalicylidene)glycinate (4) dyes. 1–4 correspond to a class of N-salicylidene aniline derivatives, whose photophysical properties are dictated by the intramolecular proton transfer between the OH-function and the imine N-atom, affording tautomerization between the enol-imine and keto-enamine forms. Photophysical properties of 1–4 were studied in different pure non-polar and (a)protic polar solvents as well as upon gradual addition of NEt3, NaOH, and CH3SO3H. The DFT calculations were performed to verify the structures of 1–4 as well as their electronic and optical properties.
A Perfect Plastic Material for Studies on Self-Propelled Motion on the Water Surface
Authors: Löffler Richard J. G. , Hanczyc Martin M. , Gorecki Jerzy
Published: May 2021

We describe a novel plastic material composed of camphene, camphor, and polypropylene that seems perfectly suited for studies on self-propelled objects on the water surface. Self-motion is one of the attributes of life, and chemically propelled objects show numerous similarities with animated motion. One of important questions is the relationship between the object shape and its motility. In our paper published in 2019, we presented a novel hybrid material, obtained from the solution of camphor in camphene, that allowed making objects of various shapes. This hybrid material has wax-like mechanical properties, but it has a very high tackiness. Here, we report that a small amount of polypropylene removed this undesirable feature. We investigated the properties of camphor–camphene–polypropylene plastic by performing the statistical analysis of a pill trajectory inside a Petri dish and compared them with those of camphor-camphene wax. The plastic showed the stable character of motion for over an hour-long experiment. The surface activity of objects made of plastic did not significantly depend on the weight ratios of the compounds. Such a significant increase in usefulness came from the polypropylene, which controlled the dissipation of camphor and camphene molecules.
Blockade of NF-κB Translocation and of RANKL/RANK Interaction Decreases the Frequency of Th2 and Th17 Cells Capable of IL-4 and IL-17 Production, Respectively, in a Mouse Model of Allergic Asthma
Authors: Gregorczyk Izabela , Jasiecka-Mikołajczyk Agnieszka , Maślanka Tomasz
Published: May 2021

The main purpose of this study was to investigate whether the blockade of the interaction between the receptor activator of nuclear factor-κB (NF-ĸB) ligand (RANKL) and its receptor RANK as well as the blockade of NF-κB inhibitor kinase (IKK) and of NF-κB translocation have the potential to suppress the pathogenesis of allergic asthma by inhibition and/or enhancement of the production by CD4+ and CD8+ T cells of important cytokines promoting (i.e., IL-4 and IL-17) and/or inhibiting (i.e., IL-10 and TGF-β), respectively, the development of allergic asthma. Studies using ovalbumin(OVA)-immunized mice have demonstrated that all the tested therapeutic strategies prevented the OVA-induced increase in the absolute number of IL-4- and IL-17-producing CD4+ T cells (i.e., Th2 and Th17 cells, respectively) indirectly, i.e., through the inhibition of the clonal expansion of these cells in the mediastinal lymph nodes. Additionally, the blockade of NF-κB translocation and RANKL/RANK interaction, but not IKK, prevented the OVA-induced increase in the percentage of IL-4-, IL-10- and IL-17-producing CD4+ T cells. These latter results strongly suggest that both therapeutic strategies can directly decrease IL-4 and IL-17 production by Th2 and Th17 cells, respectively. This action may constitute an important mechanism underlying the anti-asthmatic effect induced by the blockade of NF-κB translocation and of RANKL/RANK interaction. Thus, in this context, both these therapeutic strategies seem to have an advantage over the blockade of IKK. None of the tested therapeutic strategies increased both the absolute number and frequency of IL-10- and TGF-β-producing Treg cells, and hence they lacked the potential to inhibit the development of the disease via this mechanism.
Controlled Biosynthesis of ZnCdS Quantum Dots with Visible-Light-Driven Photocatalytic Hydrogen Production Activity
Authors: Qi Shiyue , Miao Yahui , Chen Ji , Chu Huichao , Tian Bingyang , Wu Borong , Li Yanju , Xin Baoping
Published: May 2021

The development of visible-light-responsive photocatalysts with high efficiency, stability, and eco-friendly nature is beneficial to the large-scale application of solar hydrogen production. In this work, the production of biosynthetic ternary ZnCdS photocatalysts (Eg = 2.35–2.72 eV) by sulfate-reducing bacteria (SRB) under mild conditions was carried out for the first time. The huge amount of biogenic S2− and inherent extracellular proteins (EPs) secreted by SRB are important components of rapid extracellular biosynthesis. The ternary ZnCdS QDs at different molar ratios of Zn2+and Cd2+ from 15:1 to 1:1 were monodisperse spheres with good crystallinity and average crystallite size of 6.12 nm, independent of the molar ratio of Cd2+ to Zn2+. All the ZnCdS QDs had remarkable photocatalytic activity and stability for hydrogen evolution under visible light, without noble metal cocatalysts. Especially, ZnCdS QDs at Zn/Cd = 3:1 showed the highest H2 production activity of 3.752 mmol·h−1·g−1. This excellent performance was due to the high absorption of visible light, the high specific surface area, and the lower recombination rate between photoexcited electrons and holes. The adhered inherent EPs on the ZnCdS QDs slowed down the photocorrosion and improved the stability in photocatalytic hydrogen evolution. This study provides a new direction for solar hydrogen production.
Influence of Physicochemical Characteristics and Stability of Gold and Silver Nanoparticles on Biological Effects and Translocation across an Intestinal Barrier—A Case Study from In Vitro to In Silico
Authors: Kohl Yvonne , Hesler Michelle , Drexel Roland , Kovar Lukas , Dähnhardt-Pfeiffer Stephan , Selzer Dominik , Wagner Sylvia , Lehr Thorsten , von Briesen Hagen , Meier Florian
Published: May 2021

A better understanding of their interaction with cell-based tissue is a fundamental prerequisite towards the safe production and application of engineered nanomaterials. Quantitative experimental data on the correlation between physicochemical characteristics and the interaction and transport of engineered nanomaterials across biological barriers, in particular, is still scarce, thus hampering the development of effective predictive non-testing strategies. Against this background, the presented study investigated the translocation of gold and silver nanoparticles across the gastrointestinal barrier along with related biological effects using an in vitro 3D-triple co-culture cell model. Standardized in vitro assays and quantitative polymerase chain reaction showed no significant influence of the applied nanoparticles on both cell viability and generation of reactive oxygen species. Transmission electron microscopy indicated an intact cell barrier during the translocation study. Single particle ICP-MS revealed a time-dependent increase of translocated nanoparticles independent of their size, shape, surface charge, and stability in cell culture medium. This quantitative data provided the experimental basis for the successful mathematical description of the nanoparticle transport kinetics using a non-linear mixed effects modeling approach. The results of this study may serve as a basis for the development of predictive tools for improved risk assessment of engineered nanomaterials in the future.
Resistive Switching Characteristics Improved by Visible-Light Irradiation in a Cs2AgBiBr6-Based Memory Device
Authors: Lv Fengzhen , Zhong Tingting , Qin Yongfu , Qin Haijun , Wang Wenfeng , Liu Fuchi , Kong Wenjie
Published: May 2021

Light-modulated lead-free perovskites-based memristors, combining photoresponse and memory, are promising as multifunctional devices. In this work, lead-free double perovskite Cs2AgBiBr6 films with dense surfaces and uniform grains were prepared by the low-temperature sol-gel method on indium tin oxide (ITO) substrates. A memory device based on a lead-free double perovskite Cs2AgBiBr6 film, Pt/Cs2AgBiBr6/ITO/glass, presents obvious bipolar resistive switching behavior. The ROFF/RON ratio under 445 nm wavelength light illumination is ~100 times greater than that in darkness. A long retention capability (>2400 s) and cycle-to-cycle consistency (>500 times) were observed in this device under light illumination. The resistive switching behavior is primarily attributed to the trap-controlled space-charge-limited current mechanism caused by bromine vacancies in the Cs2AgBiBr6 medium layer. Light modulates resistive states by regulating the condition of photo-generated carriers and changing the Schottky-like barrier of the Pt/Cs2AgBiBr6 interface under bias voltage sweeping.
Correction: Mahmoud et al. Interaction of Gold Nanorods with Human Dermal Fibroblasts: Cytotoxicity, Cellular Uptake, and Wound Healing. Nanomaterials 2019, 9, 1131
Authors: Mahmoud Nouf N. , Al-Kharabsheh Lubna M. , Khalil Enam A. , Abu-Dahab Rana
Published: May 2021

The authors wish to make the following correction to Figure 1 D in this paper [...]
Thickness-Dependent Photoelectrochemical Water Splitting Properties of Self-Assembled Nanostructured LaFeO3 Perovskite Thin Films
Authors: Andrei Florin , Ion Valentin , Bîrjega Ruxandra , Dinescu Maria , Enea Nicoleta , Pantelica Dan , Mihai Maria Diana , Maraloiu Valentin-Adrian , Teodorescu Valentin Serban , Marcu Ioan-Cezar , Scarisoreanu Nicu Doinel
Published: May 2021

Tuning the intrinsic structural and stoichiometric properties by different means is used for increasing the green energy production efficiency of complex oxide materials. Here, we report on the formation of self-assembled nanodomains and their effects on the photoelectrochemical (PEC) properties of LaFeO3 (LFO) epitaxial thin films as a function of layer’s thickness. The variation with the film’s thickness of the structural parameters such as in-plane and out-of-plane crystalline coherence length and the coexistence of different epitaxial orientation—<100>SrTiO3//<001> LFO, <100>SrTiO3//<110> LFO and [110] LFO//[10] STO, as well as the appearance of self-assembled nanodomains for film’s thicknesses higher than 14 nm, is presented. LFO thin films exhibit different epitaxial orientations depending on their thickness, and the appearance of self-assembled nanopyramids-like domains after a thickness threshold value has proven to have a detrimental effect on the PEC functional properties. Using Nb:SrTiO3 as conductive substrate and 0.5 M NaOH aqueous solution for PEC measurements, the dependence of the photocurrent density and the onset potential vs. RHE on the structural and stoichiometric features exhibited by the LFO photoelectrodes are unveiled by the X-ray diffraction, high-resolution transmission electron microscopy, ellipsometry, and Rutherford backscattering spectroscopy results. The potentiodynamic PEC analysis has revealed the highest photocurrent density Jphotocurrent values (up to 1.2 mA/cm2) with excellent stability over time, for the thinnest LFO/Nb:SrTiO3 sample, both cathodic and anodic behavior being noticed. Noticeably, the LFO thin film shows unbiased hydrogen evolution from water, as determined by gas chromatography in aqueous 0.5 M NaOH solution under constant illumination.
Plasma Electrolytic Oxidation (PEO) Process—Processing, Properties, and Applications
Authors: Sikdar Soumya , Menezes Pramod V. , Maccione Raven , Jacob Timo , Menezes Pradeep L.
Published: May 2021

Plasma electrolytic oxidation (PEO) is a novel surface treatment process to produce thick, dense metal oxide coatings, especially on light metals, primarily to improve their wear and corrosion resistance. The coating manufactured from the PEO process is relatively superior to normal anodic oxidation. It is widely employed in the fields of mechanical, petrochemical, and biomedical industries, to name a few. Several investigations have been carried out to study the coating performance developed through the PEO process in the past. This review attempts to summarize and explain some of the fundamental aspects of the PEO process, mechanism of coating formation, the processing conditions that impact the process, the main characteristics of the process, the microstructures evolved in the coating, the mechanical and tribological properties of the coating, and the influence of environmental conditions on the coating process. Recently, the PEO process has also been employed to produce nanocomposite coatings by incorporating nanoparticles in the electrolyte. This review also narrates some of the recent developments in the field of nanocomposite coatings with examples and their applications. Additionally, some of the applications of the PEO coatings have been demonstrated. Moreover, the significance of the PEO process, its current trends, and its scope of future work are highlighted.
Interaction between Graphene-Based Materials and Small Ag, Cu, and CuO Clusters: A Molecular Dynamics Study
Authors: Lado-Touriño Isabel , Páez-Pavón Alicia
Published: May 2021

The excessive use of antibiotics has contributed to the rise in antibiotic-resistant bacteria, and thus, new antibacterial compounds must be developed. Composite materials based on graphene and its derivatives doped with metallic and metallic oxide nanoparticles, particularly Ag, Cu, and Cu oxides, hold great promise. These materials are often modified with polyethylene glycol (PEG) to improve their pharmacokinetic behavior and their solubility in biological media. In this work, we performed molecular dynamics (MD) simulations to study the interaction between small Ag, Cu, and CuO clusters and several graphene-based materials. These materials include pristine graphene (PG) and pristine graphene nanoplatelets (PGN) as well as PEGylated graphene oxide (GO_PEG) and PEGylated graphene oxide nanoplatelets (GO-PEG_N). We calculated the adsorption energies, mean equilibrium distances between the nanoparticles and graphene surfaces, and mean square displacement (MSD) of the nanoclusters. The results show that PEGylation favors the adsorption of the clusters on the graphene surfaces, causing an increase in adsorption energies and a decrease in both distances and MSD values. The strengthening of the interaction could be crucial to obtain effective antibacterial compounds.
Single-Pixel Photon-Counting Imaging Based on Dual-Comb Interferometry
Authors: Hu Huiqin , Ren Xinyi , Wen Zhaoyang , Li Xingtong , Liang Yan , Yan Ming , Wu E
Published: May 2021

We propose and experimentally demonstrate single-pixel photon counting imaging based on dual-comb interferometry at 1550 nm. Different from traditional dual-comb imaging, this approach enables imaging at the photon-counting regime by using single-photon detectors combined with a time-correlated single-photon counter to record the returning photons. The illumination power is as low as 14 pW, corresponding to 2.2 × 10−3 photons/pulse. The lateral resolution is about 50 μm. This technique paves the way for applying dual-comb in remote sensing and imaging.
Iron Oxide Nanorings and Nanotubes for Magnetic Hyperthermia: The Problem of Intraparticle Interactions
Authors: Das Raja , Masa Javier Alonso , Kalappattil Vijaysankar , Nemati Zohreh , Rodrigo Irati , Garaio Eneko , García José Ángel , Phan Manh-Huong , Srikanth Hariharan
Published: May 2021

Magnetic interactions can play an important role in the heating efficiency of magnetic nanoparticles. Although most of the time interparticle magnetic interactions are a dominant source, in specific cases such as multigranular nanostructures intraparticle interactions are also relevant and their effect is significant. In this work, we have prepared two different multigranular magnetic nanostructures of iron oxide, nanorings (NRs) and nanotubes (NTs), with a similar thickness but different lengths (55 nm for NRs and 470 nm for NTs). In this way, we find that the NTs present stronger intraparticle interactions than the NRs. Magnetometry and transverse susceptibility measurements show that the NTs possess a higher effective anisotropy and saturation magnetization. Despite this, the AC hysteresis loops obtained for the NRs (0–400 Oe, 300 kHz) are more squared, therefore giving rise to a higher heating efficiency (maximum specific absorption rate, SARmax = 110 W/g for the NRs and 80 W/g for the NTs at 400 Oe and 300 kHz). These results indicate that the weaker intraparticle interactions in the case of the NRs are in favor of magnetic hyperthermia in comparison with the NTs.
The Moderating Effects of the Families Improving Together (FIT) for Weight Loss Intervention and Parenting Factors on Family Mealtime in Overweight and Obese African American Adolescents
Authors: Wilson Dawn K. , Sweeney Allison M. , Quattlebaum Mary , Loncar Haylee , Kipp Colby , Brown Asia
Published: May 2021

Few studies have integrated positive parenting and motivational strategies to address dietary outcomes such as frequency of family mealtime. The Families Improving Together (FIT) for Weight Loss trial was a randomized group cohort trial (n = 241 dyads) testing the efficacy of integrating a motivational plus family weight loss (M + FWL) intervention for healthy eating and weight loss in overweight and obese African American adolescents. The current study tested the interaction of parenting styles (responsiveness, demandingness) and parental feeding practices (restriction, concern about child’s weight, pressure to eat) and the FIT intervention on frequency of family mealtime over 16 weeks. Multilevel modeling demonstrated significant interactions between the group-based treatment and responsiveness (p = 0.018) and demandingness (p = 0.010) on family mealtime. For the group-based M + FWL intervention, increased responsiveness and reduced demandingness were associated with increased frequency of family mealtime from baseline to 16 weeks. There was also a negative association between parental restriction and frequency of family mealtime, but a positive association between parental concerns about their adolescent’s weight and frequency of mealtime. These findings are the first to demonstrate that an authoritative or nurturing parenting style moderated intervention effects for improving the frequency of family mealtime in overweight and obese African American adolescents.
Nutritional Regulation of Human Brown Adipose Tissue
Authors: Suchacki Karla J. , Stimson Roland H.
Published: May 2021

The recent identification of brown adipose tissue in adult humans offers a new strategy to increase energy expenditure to treat obesity and associated metabolic disease. While white adipose tissue (WAT) is primarily for energy storage, brown adipose tissue (BAT) is a thermogenic organ that increases energy expenditure to generate heat. BAT is activated upon cold exposure and improves insulin sensitivity and lipid clearance, highlighting its beneficial role in metabolic health in humans. This review provides an overview of BAT physiology in conditions of overnutrition (obesity and associated metabolic disease), undernutrition and in conditions of altered fat distribution such as lipodystrophy. We review the impact of exercise, dietary macronutrients and bioactive compounds on BAT activity. Finally, we discuss the therapeutic potential of dietary manipulations or supplementation to increase energy expenditure and BAT thermogenesis. We conclude that chronic nutritional interventions may represent a useful nonpharmacological means to enhance BAT mass and activity to aid weight loss and/or improve metabolic health.
The Efficacy of Short-Term Weight Loss Programs and Consumption of Natural Probiotic Bryndza Cheese on Gut Microbiota Composition in Women
Authors: Hric Ivan , Ugrayová Simona , Penesová Adela , Rádiková Žofia , Kubáňová Libuša , Šardzíková Sára , Baranovičová Eva , Klučár Ľuboš , Beke Gábor , Grendar Marian , Kolisek Martin , Šoltys Katarína , Bielik Viktor
Published: May 2021

Weight loss interventions with probiotics have favourable effects on gut microbiota composition and derived metabolites. However, little is known about whether the consumption of natural probiotics, such as Bryndza cheeses, brings similar benefits. The purpose of the study was to find the effect of short-term weight loss programs and Bryndza cheese consumption on the structure of the gut microbiota, microbiota-derived metabolites and body composition in middle-aged women. We conducted a randomised controlled intervention study. Twenty-two female participants with a body fat percentage ≥25% underwent a short weight loss program (4 weeks). Subjects were randomised to either the control or intervention group according to diet. The intervention group comprised 13 participants, whose diet contained 30 g of “Bryndza” cheese daily (WLPB). The control group comprised nine participants without the regular consumption of Bryndza cheese (WLP) in their diet. Both interventions lead to a significant and favourable change of BMI, body fat, waist circumference and muscle mass. Moreover, the relative abundance of Erysipelotrichales significantly increased in both groups. However, the relative abundance of lactic acid bacteria (Lactobacillales, Streptococcaceae, Lactococcus and Streptococcus) significantly increased only in the WLPB group. Furthermore, short-chain fatty acid producers Phascolarctobacterium and Butyricimonas increased significantly in the WLPB group. A short-term weight loss program combined with Bryndza cheese consumption improves body composition and increases the abundance of lactic acid bacteria and short-chain fatty acid producers in middle-aged women.
Availability of a Flavored Beverage and Impact on Children’s Hydration Status, Sleep, and Mood
Authors: Szymanski Michael R. , Giersch Gabrielle E. W. , Morrissey Margaret C. , Benjamin Courteney L. , Sekiguchi Yasuki , Manning Ciara N. , Stearns Rebecca L. , Casa Douglas J.
Published: May 2021

Euhydration remains a challenge in children due to lack of access and unpalatability of water and to other reasons. The purpose of this study was to determine if the availability/access to a beverage (Creative Roots®) influences hydration in children and, therefore, sleep quality and mood. Using a crossover investigation, 46 participants were randomly assigned to a control group (CON) or an intervention group and received Creative Roots® (INT) for two-week periods. We recorded daily first morning and afternoon urine color (Ucol), thirst perception, and bodyweight of the two groups. Participants reported to the lab once per week and provided first morning urine samples to assess Ucol, urine specific gravity (USG), and urine osmolality (Uosmo). Participants also completed the questionnaires Profile of Mood States-Adolescents (POMS-a) and Pittsburgh Sleep Quality Index (PSQI). Dependent t-tests were used to assess the effects of the intervention on hydration, mood, and sleep quality. Uosmo was greater and Ucol was darker in the control group (mean ± SD) [Uosmo: INT = 828 ± 177 mOsm·kg−1, CON = 879 ± 184 mOsm·kg−1, (p = 0.037], [Ucol:INT = 5 ± 1, CON = 5 ± 1, p = 0.024]. USG, POMS-a, and PSQI were not significant between the groups. At-home daily afternoon Ucol was darker in the control group [INT = 3 ± 1, CON = 3 ± 1, p = 0.022]. Access to Creative Roots® provides a small, potentially meaningful hydration benefit in children. However, children still demonstrated consistent mild dehydration based on Uosmo, despite consuming the beverage.
Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study
Authors: Alcala-Diaz Juan F. , Limia-Perez Laura , Gomez-Huelgas Ricardo , Martin-Escalante Maria D. , Cortes-Rodriguez Begoña , Zambrana-Garcia Jose L. , Entrenas-Castillo Marta , Perez-Caballero Ana I. , López-Carmona Maria D. , Garcia-Alegria Javier , Lozano Rodríguez-Mancheño Aquiles , Arenas-de Larriva Maria del Sol , Pérez-Belmonte Luis M. , Jungreis Irwin , Bouillon Roger , Quesada-Gomez Jose Manual , Lopez-Miranda Jose
Published: May 2021

Context. Calcifediol has been proposed as a potential treatment for COVID-19 patients. Objective: To compare the administration or not of oral calcifediol on mortality risk of patients hospitalized because of COVID-19. Design: Retrospective, multicenter, open, non-randomized cohort study. Settings: Hospitalized care. Patients: Patients with laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the South of Spain. Intervention: Patients received calcifediol (25-hydroxyvitamin D3) treatment (0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or not. Main Outcome Measure: In-hospital mortality during the first 30 days after admission. Results: A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol (mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving such treatment (mortality rate of 20%; p < 0.01). Patients who received calcifediol after admission were more likely than those not receiving treatment to have comorbidity and a lower rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg, and age ≥ 65 years), acute respiratory distress syndrome (moderate or severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a multivariable logistic regression model, adjusting for confounders, there were significant differences in mortality for patients receiving calcifediol compared with patients not receiving it (OR = 0.16 (95% CI 0.03 to 0.80). Conclusion: Among patients hospitalized with COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was significantly associated with lower in-hospital mortality during the first 30 days. The observational design and sample size may limit the interpretation of these findings.
Triglyceride-Rich Lipoproteins and Their Remnants as Silent Promoters of Atherosclerotic Cardiovascular Disease and Other Metabolic Disorders: A Review
Authors: Sascău Radu , Clement Alexandra , Radu Rodica , Prisacariu Cristina , Stătescu Cristian
Published: May 2021

While targeting elevated serum levels of low-density lipoprotein cholesterol has been the mainstay of atherosclerosis prevention and treatment for decades, the evidence regarding the atherogenic role of hypertriglyceridemia is still controversial. Various epidemiological population-based studies on statin-treated subjects nominated triglycerides, triglyceride-rich lipoproteins (namely, chylomicrons and very-low-density lipoprotein particles), and their remnants as major determinants of the substantial residual cardiovascular risk. With the triglyceride-glucose index and triglyceride to high-density lipoprotein ratio emerging as surrogate indicators of peripheral artery disease and atherosclerotic cerebrovascular disease, one can conclude that further research addressing the intricate relationship between triglycerides and atherosclerosis is warranted. Therefore, this review aims to provide insight into the current clinical and epidemiological state of knowledge on the relationship between triglycerides and atherosclerotic cardiovascular disease. It also intends to highlight the connection between triglycerides and other metabolic disorders, including diabetes mellitus, and the potential benefits of triglyceride-lowering agents on cardiovascular outcomes and all-cause mortality.
Human Milk Virome Analysis: Changing Pattern Regarding Mode of Delivery, Birth Weight, and Lactational Stage
Authors: Dinleyici Meltem , Pérez-Brocal Vicente , Arslanoglu Sertac , Aydemir Ozge , Sevuk Ozumut Sibel , Tekin Neslihan , Vandenplas Yvan , Moya Andrés , Dinleyici Ener Cagri
Published: May 2021

The human milk (HM) microbiota is a significant source of microbes that colonize the infant gut early in life. The aim of this study was to compare transient and mature HM virome compositions, and also possible changes related to the mode of delivery, gestational age, and weight for gestational age. Overall, in the 81 samples analyzed in this study, reads matching bacteriophages accounted for 79.5% (mainly Podoviridae, Myoviridae, and Siphoviridae) of the reads, far more abundant than those classified as eukaryotic viruses (20.5%, mainly Herpesviridae). In the whole study group of transient human milk, the most abundant families were Podoviridae and Myoviridae. In mature human milk, Podoviridae decreased, and Siphoviridae became the most abundant family. Bacteriophages were predominant in transient HM samples (98.4% in the normal spontaneous vaginal delivery group, 92.1% in the premature group, 89.9% in the C-section group, and 68.3% in the large for gestational age group), except in the small for gestational age group (only ~45% bacteriophages in transient HM samples). Bacteriophages were also predominant in mature HM; however, they were lower in mature HM than in transient HM (71.7% in the normal spontaneous vaginal delivery group, 60.8% in the C-section group, 56% in the premature group, and 80.6% in the large for gestational age group). Bacteriophages still represented 45% of mature HM in the small for gestational age group. In the transient HM of the normal spontaneous vaginal delivery group, the most abundant family was Podoviridae; however, in mature HM, Podoviridae became less prominent than Siphoviridae. Myoviridae was predominant in both transient and mature HM in the premature group (all C-section), and Podoviridae was predominant in transient HM, while Siphoviridae and Herpesviridae were predominant in mature HM. In the small for gestational age group, the most abundant taxa in transient HM were the family Herpesviridae and a species of the genus Roseolovirus. Bacteriophages constituted the major component of the HM virome, and we showed changes regarding the lactation period, preterm birth, delivery mode, and birth weight. Early in life, the HM virome may influence the composition of an infant’s gut microbiome, which could have short- and long-term health implications. Further longitudinal mother–newborn pair studies are required to understand the effects of these variations on the composition of the HM and the infant gut virome.
Prevalence of Metabolic Syndrome in Children and Adolescents with Type 1 Diabetes Mellitus and Possibilities of Prevention and Treatment: A Systematic Review
Authors: Grabia Monika , Markiewicz-Żukowska Renata , Socha Katarzyna
Published: May 2021

Overweight and obesity are an increasingly common problem, not only among the healthy population, but also in adolescents with type 1 diabetes (T1DM). Excess body weight is related to many cardiometabolic complications as well as a high risk of metabolic syndrome (MetS). The purpose of this systematic review is to provide a concise and critical overview of the prevalence of MetS in children and adolescents with T1DM and, ultimately, to discuss prevention and treatment options. The study was conducted in accordance with PRISMA guidelines. This review shows that, apart from the growing percentage of overweight and obese children and adolescents with T1DM (on average 20.1% and 9.5%, respectively), the problem of the increasing incidence of MetS (range from 3.2 to 29.9%, depending on the criteria used) is one of the most important phenomena of our time. One of the methods of prevention and treatment is a combined approach: changing eating habits and lifestyle, but there are also reports about the beneficial effects of the gut microflora.
Management of Hypnotics in Patients with Insomnia and Heart Failure during Hospitalization: A Systematic Review
Authors: Jorge-Samitier Pablo , Fernández-Rodrigo María Teresa , Juárez-Vela Raúl , Antón-Solanas Isabel , Gea-Caballero Vicente
Published: May 2021

Background: Heart failure is a chronic, progressive syndrome of signs and symptoms, which has been associated to a range of comorbidities including insomnia. Acute decompensation of heart failure frequently leads to hospital admission. During hospital admission, long-term pharmacological treatments such as hypnotics can be modified or stopped. Aim: To synthesize the scientific evidence available about the effect of withdrawing hypnotic drugs during hospital admission in patients with decompensated heart failure and insomnia. Method: A systematic review of the literature following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was carried out in the following scientific databases: PubMed, Scopus, Dialnet and Cochrane. Inclusion criteria: studies including a population of adults with heart failure and sleep disorders in treatment with hypnotics and admitted to hospital, studies written in English or Spanish and published until June 2020. Exclusion criteria: studies involving children, patients admitted to intensive care and patients diagnosed with sleep apnea. Results: We identified a total of 265 documents; only nine papers met the selection criteria. The most frequently used drugs for the treatment of insomnia in patients with heart failure were benzodiazepines and benzodiazepine agonists; their secondary effects can alter perceived quality of life and increase the risk of adverse effects. Withdrawal of these drugs during hospital admission could increase the risk of delirium. Future research in this area should evaluate the management of hypnotics during hospital admission in patients with decompensated heart failure. In addition, safe and efficient non-pharmacological alternatives for the treatment of insomnia in this population should be tested and implemented.
Investigating the Presence of SARS CoV-2 in Free-Living and Captive Animals
Authors: Jemeršić Lorena , Lojkić Ivana , Krešić Nina , Keros Tomislav , Zelenika Tajana Amšel , Jurinović Luka , Skok Damir , Bata Ingeborg , Boras Jadranko , Habrun Boris , Brnić Dragan
Published: May 2021

Due to SARS CoV-2 recombination rates, number of infected people and recent reports of environmental contamination, the possibility of SARS CoV-2 transmission to animals can be expected. We tested samples of dominant free-living and captive wildlife species in Croatia for the presence of anti-SARS CoV-2 antibodies and viral RNA. In total, from June 2020 until February 2021, we tested blood, muscle extract and fecal samples of 422 free-living wild boars (Sus scrofa), red foxes (Vulpes vulpes) and jackals (Canis aureus); blood and cloacal swabs of 111 yellow-legged gulls (Larus michahellis) and fecal samples of 32 zoo animals. A commercially available ELISA (ID.Vet, France) and as a confirmatory test, a surrogate virus neutralization test (sVNT; GenScript, Netherlands) were used. Fecal samples were tested for the presence of viral RNA by a real-time RT–PCR protocol. Fifteen out of 533 (2.8%) positive ELISA results were detected; in wild boars (3.9%), red foxes (2.9%) and jackals (4.6%). However, the positive findings were not confirmed by sVNT. No viral RNA was found. In conclusion, no spillover occurred within the investigated period (second COVID-19 wave). However, further investigation is needed, especially regarding wildlife sample features for serological tests.
Detection of Anti-Nucleocapsid Antibody in COVID-19 Patients in Bangladesh Is not Correlated with Previous Dengue Infection
Authors: Lytton Simon D. , Yeasmin Mahmuda , Ghosh Asish Kumar , Bulbul Md. Rakibul Hassan , Molla Md. Maruf Ahmed , Herr Martha , Duchmann Helmut , Sharif Md. Mohiuddin , Nafisa Tasnim , Amin Md. Robed , Hosen Nur , Rahman Md. Tanvir , Islam Sumaiya , Islam Alimul , Shamsuzzaman Abul Khair Mohammad
Published: May 2021

Background: The assessment of antibody responses to severe acute respiratory syndrome coronavirus-2 is potentially confounded by exposures to flaviviruses. The aims of the present research were to determine whether anti-dengue antibodies affect the viral load and the detection of anti-coronavirus nucleocapsid (N)-protein antibodies in coronavirus infectious disease 2019 (COVID-19) in Bangladesh. Methods: Viral RNA was evaluated in swab specimens from 115 COVID-19 patients by real-time reverse transcription polymerase chain reaction (rT-PCR). The anti-N-protein antibodies, anti-dengue virus E-protein antibodies and the dengue non-structural protein-1 were determined in serum from 115 COVID-19 patients, 30 acute dengue fever pre-COVID-19 pandemic and nine normal controls by ELISA. Results: The concentrations of viral RNA in the nasopharyngeal; Ct median (95% CI); 22 (21.9–23.3) was significantly higher than viral RNA concentrations in oropharyngeal swabs; and 29 (27–30.5) p < 0.0001. Viral RNA concentrations were not correlated with-dengue IgG levels. The anti-nucleocapsid antibodies were IgA 27% positive and IgG 35% positive at days 1 to 8 post-onset of COVID-19 symptoms versus IgA 0% and IgG 0% in dengue patients, p < 0.0001. The levels of anti- nucleocapsid IgA or IgG versus the levels of anti-dengue IgM or IgG revealed no significant correlations. Conclusions: Viral RNA and anti-nucleocapsid antibodies were detected in COVID-19 patients from dengue-endemic regions of Bangladesh, independently of the dengue IgG levels.
Identification of an Attenuated Substrain of Francisella tularensis SCHU S4 by Phenotypic and Genotypic Analyses
Authors: Lovchik Julie A. , Reed Douglas S. , Hutt Julie A. , Xia Fangfang , Stevens Rick L. , Modise Thero , Barry Eileen M. , Wu Terry H.
Published: May 2021

Pneumonic tularemia is a highly debilitating and potentially fatal disease caused by inhalation of Francisella tularensis. Most of our current understanding of its pathogenesis is based on the highly virulent F. tularensis subsp. tularensis strain SCHU S4. However, multiple sources of SCHU S4 have been maintained and propagated independently over the years, potentially generating genetic variants with altered virulence. In this study, the virulence of four SCHU S4 stocks (NR-10492, NR-28534, NR-643 from BEI Resources and FTS-635 from Battelle Memorial Institute) along with another virulent subsp. tularensis strain, MA00-2987, were assessed in parallel. In the Fischer 344 rat model of pneumonic tularemia, NR-643 and FTS-635 were found to be highly attenuated compared to NR-10492, NR-28534, and MA00-2987. In the NZW rabbit model of pneumonic tularemia, NR-643 caused morbidity but not mortality even at a dose equivalent to 500x the LD50 for NR-10492. Genetic analyses revealed that NR-10492 and NR-28534 were identical to each other, and nearly identical to the reference SCHU S4 sequence. NR-643 and FTS-635 were identical to each other but were found to have nine regions of difference in the genomic sequence when compared to the published reference SCHU S4 sequence. Given the genetic differences and decreased virulence, NR-643/FTS-635 should be clearly designated as a separate SCHU S4 substrain and no longer utilized in efficacy studies to evaluate potential vaccines and therapeutics against tularemia.
Detection of Tick-Borne Pathogens in Red Deer (Cervus elaphus), United Kingdom
Authors: Johnson Nicholas , Golding Megan , Phipps Laurence Paul
Published: May 2021

Deer represent a major vertebrate host for all feeding stages of the hard tick Ixodes ricinus in the United Kingdom (UK), and could play a role in the persistence of tick-borne pathogens. However, there have been few studies reporting the presence of Babesia spp. and Anaplasma phagocytophilum in deer in the UK, and those that detected Babesia were unable to confirm the species. To address this, we have investigated blood samples from red deer (Cervus elaphus) for the presence of tick-borne pathogens. Total DNA was extracted from haemolysed blood that was removed from clotted blood sampled from culled, captive red deer. Babesia spp. were detected with a pan-piroplasm PCR that amplifies a fragment of the 18S rRNA gene. Species were identified based on identity with published sequences. Anaplasma phagocytophilum was detected with a probe-based PCR targeting the msp2 gene. In addition, residual serum samples from a subset of animals were tested for the presence of anti-flavivirus antibodies. Of 105 red deer samples tested from three locations in the United Kingdom, 5 were positive for piroplasm and 5 were positive for A. phagocytophilum. Co-infection with both pathogens was detected in two samples from one location. No evidence for antibodies against West Nile virus were detected. However, 12% of sera tested were positive for tick-borne encephalitis virus antibodies.