bluuebunny/crossref_metadata_2025 huggingface dataset:
(−)-Loliolide Isolated from Sargassum horneri Abate UVB-Induced Oxidative Damage in Human Dermal Fibroblasts and Subside ECM Degradation
Authors: Fernando Ilekuttige Priyan Shanura , Heo Soo-Jin , Dias Mawalle Kankanamge Hasitha Madhawa , Madusanka Dissanayaka Mudiyanselage Dinesh , Han Eui-Jeong , Kim Min-Ju , Sanjeewa Kalu Kapuge Asanka , Lee Kyounghoon , Ahn Ginnae
Published: July 2021

Ultraviolet (UV) B exposure is a prominent cause of skin aging and a contemporary subject of interest. The effects are progressing through the generation of reactive oxygen species (ROS) that alter cell signaling pathways related to inflammatory responses. The present study evaluates the protective effects of (7aR)-6-hydroxy-4,4,7a-trimethyl-6,7-dihydro-5H-1-benzofuran-2-one (HTT) isolated from the edible brown algae Sargassum horneri against UVB protective effects in human dermal fibroblasts (HDFs). HTT treatment dose-dependently suppressed intracellular ROS generation in HDFs with an IC50 of 62.43 ± 3.22 µM. HTT abated UVB-induced mitochondrial hyperpolarization and apoptotic body formation. Furthermore, UVB-induced activation of key nuclear factor (NF)-κB and mitogen-activated protein kinase signaling proteins were suppressed in HTT treated cells while downregulating pro-inflammatory cytokines (interleukin-1β, 6, 8, 33 and tumor necrosis factor-α). Moreover, HTT treatment downregulated matrix metalloproteinase1, 2, 3, 8, 9 and 13 that was further confirmed by the inhibition of collagenase and elastase activity. The evidence implies that HTT delivers protective effects against premature skin aging caused by UVB exposure via suppressing inflammatory responses and degradation of extracellular matrix (ECM) components. Extensive research in this regard will raise perspectives for using HTT as an ingredient in UV protective ointments.
Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer
Authors: Peyrottes Arthur , Ouzaid Idir , Califano Gianluigi , Hermieu Jean-Francois , Xylinas Evanguelos
Published: July 2021

Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative immunotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.
Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review
Authors: Piccioni Andrea , Santoro Michele Cosimo , de Cunzo Tommaso , Tullo Gianluca , Cicchinelli Sara , Saviano Angela , Valletta Federico , Pascale Marco Maria , Candelli Marcello , Covino Marcello , Franceschi Francesco
Published: July 2021

The diagnosis and treatment of sepsis have always been a challenge for the physician, especially in critical care setting such as emergency department (ED), and currently sepsis remains one of the major causes of mortality. Although the traditional definition of sepsis based on systemic inflammatory response syndrome (SIRS) criteria changed in 2016, replaced by the new criteria of SEPSIS-3 based on organ failure evaluation, early identification and consequent early appropriated therapy remain the primary goal of sepsis treatment. Unfortunately, currently there is a lack of a foolproof system for making early sepsis diagnosis because conventional diagnostic tools like cultures take a long time and are often burdened with false negatives, while molecular techniques require specific equipment and have high costs. In this context, biomarkers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT), are very useful tools to distinguish between normal and pathological conditions, graduate the disease severity, guide treatment, monitor therapeutic responses and predict prognosis. Among the new emerging biomarkers of sepsis, Presepsin (P-SEP) appears to be the most promising. Several studies have shown that P-SEP plasma levels increase during bacterial sepsis and decline in response to appropriate therapy, with sensitivity and specificity values comparable to those of PCT. In neonatal sepsis, P-SEP compared to PCT has been shown to be more effective in diagnosing and guiding therapy. Since in sepsis the P-SEP plasma levels increase before those of PCT and since the current methods available allow measurement of P-SEP plasma levels within 17 min, P-SEP appears a sepsis biomarker particularly suited to the emergency department and critical care.
Micro-CT and Microscopy Study of Internal and Marginal Gap to Tooth Surface of Crenelated versus Conventional Dental Indirect Veneers
Authors: Măroiu Alexandra-Cristina , Sinescu Cosmin , Duma Virgil-Florin , Topală Florin , Jivănescu Anca , Popovici Paul Mircea , Tudor Anca , Romînu Mihai
Published: July 2021

Background and Objectives: Ceramic veneers represent the most appropriate treatment option for minimally invasive aesthetic rehabilitation. For long-term clinical success, the accurate marginal and internal adaptation of dental restorations are of paramount importance. The aim of this in vitro study is to assess the effect of a novel (patented) design of veneers compared to conventional ones on their marginal and internal gap to the prepared tooth surface. Materials and Methods: Twenty-four lithium disilicate ceramic veneers are obtained using Computer-Aided-Design (CAD) and then milled using Computer-Aided-Manufacturing (CAM). The samples are divided into two groups: 12 conventional (CO) veneers (i.e., with a linear marginal contour) and 12 crenelated (CR) veneers, the latter with the novel sinusoidal marginal design. All samples are bonded to frontal teeth, and the adhesive interfaces are analyzed using two methods, optical microscopy and micro-Computed Tomography (CT): the former for the accuracy of the marginal gap and the latter for the internal gap (as well as for the homogeneity of the luting cement) of ceramic veneers. Results: STATA and one-way ANOVA tests reveal significant differences between CO and CR veneers: (i) the marginal gap is smaller for CR (64 μm) than for CO veneers (236 μm); (ii) the internal adaptation is better for CR veneers: for a cement width of up to 120 μm, the covered surface for the CR group is 81.5%, while for the CO group it is 64.5%; (iii) the mean of the porosities within the cement is not significantly different (3.4·106 μm3 for CO and 3.9·106 μm3 for CR veneers), with a higher standard deviation for the CO group. Analytical modeling is achieved for internal gaps using the micro-CT results. The characteristic functions obtained allow us to compare the volume of luting cement for the two types of veneers. Conclusion: The novel veneers design produces an improvement in the marginal and internal adaptation of the restorations to the prepared tooth surface. Thus, it provides favorable premises for better clinical performances.
Vitamin D Deficiency as a Risk Factor for Myocardial Ischemia
Authors: Batsi Christina , Gkika Evangelia , Astrakas Loukas , Papadopoulos Athanassios , Iakovou Ioannis , Dogoritis Alexandros , Fotopoulos Andreas , Sioka Chrissa
Published: July 2021

Background and Objectives: Vitamin D (Vit D) deficiency has been implicated in various conditions, including cardiovascular disease. The purpose of this retrospective study was to investigate the incidence of patients with myocardial ischemia in relation to their serum levels of vitamin D. Materials and Methods: A 64-month search (January 2016 to April 2021) in our database of the Nuclear Medicine Laboratory revealed 113 patients who had both myocardial perfusion imaging with single photon emission computed tomography (MPI SPECT) and Vit D measurements. MPI SPECT obtained myocardial images during both stress (summed stress score, SSS) and rest (summed rest score, SRS). Abnormal MPI SPECT was when the SSS was ≥4. Vit D was determined by radioimmunoassay (RIA). Patients with Vit D values <10 ng/mL, 10–29 ng/mL and ≥30 ng/mL were defined as having a deficiency, insufficiency and sufficiency, respectively. Results: Among patients, 46/113 (40.7%) were male and 67/113 (59.3%) were female. Abnormal MPI was found in 58/113 (51.3%) patients. Vit D deficiency was noted in 20/113 (17.7%) patients, insufficiency in 86/113 (76.1%) patients, and normal Vit D was noted in only 7/113 (6.2%) patients. Sixteen of the 20 patients (80%) with Vit D deficiency, and 38/86 (44.2%) with insufficiency had an abnormal MPI SPECT. In contrast, only 1/7 (14.3%) patients with sufficient Vit D levels had an abnormal MPI SPECT. The Mann-Whitney U-test showed that ischemia reduced the values of Vit D. Correlation analysis showed a negative association of Vit D levels with SSS (rho = −0.232, p = 0.014) and SRS (rho = −0.250, p = 0.008). Further evaluation with a Vit D cut off 20 ng/mL retrieved no statistical significance. Finally, Vit D and gender were independently associated with myocardial ischemia. Conclusions: Low Vit D levels may represent a risk factor for myocardial ischemia.
An Investigation into the Effect of Rolling Reduction on 3D Curved Parts Rolling Process
Authors: Chang Xiang , Fu Wenzhi , Li Mingzhe , Wang Xintong , Yang Weifeng , Deng Yushan
Published: July 2021

Rolling technology based on arc-shaped rollers is a novel method for rapid manufacturing of 3D curved parts. The method uses a pair of arc-shaped rollers (a convex roller and a concave roller) as forming tools, forming an unevenly distributed roll gap. The sheet metal has both transverse bending and longitudinal uneven extension during rolling, so that surface parts with double curvature are processed. The curvature of the formed surface part can be changed by changing the rolling reduction. Changing the vertical distance between the rollers will cause the overall change of the roll gap height, which will inevitably have a great impact on the forming effect of formed 3D curved parts. In this paper, a finite element model and experiment with different rolling reductions was designed; the influence of rolling reduction on the bending deformation and shape accuracy of formed 3D curved parts was studied. The results show that, with the slight increase of rolling reduction (from 0.04 to 0.12 mm), the longitudinal bending deformation of the formed 3D curved part increases significantly, but its transversal bending is almost not affected. When the maximum rolling reduction is 0.04 and 0.06 mm (the corresponding minimum rolling reduction is less than or equal to zero), the shape accuracy of the formed 3D curved parts is not good enough; when the maximum rolling reduction is greater than 0.06 mm (the corresponding minimum rolling reduction is greater than zero), the shape accuracy of the formed 3D curved parts is significantly better. This indicates that, for the rolling of 3D curved parts based on arc-shaped rollers, ensuring that the minimum rolling reduction is greater than zero is the key to ensuring good shape accuracy of the formed 3D curved parts.
Evolution of Inclusions in Magnesium–Calcium-Treated Liquid Iron
Authors: Shi Liwei , Zhou Xingzhi , Wang Deyong , Qu Tianpeng , Wang Huihua , Zhu Jie
Published: July 2021

With the development of clean steel technology, the control of non-metallic inclusions in steel is of increasing importance. Magnesium–calcium treatment can effectively balance the castability of molten steel and the control on inclusion size, which is an inclusion modification approach with application prospect. In view of this, how three addition methods (i.e., adding Mg before Ca, adding Mg after Ca, and adding Mg together with Ca) influenced the modification effect of inclusions in liquid iron was experimentally studied, and how these inclusions evolved with time was discussed in this paper. The results demonstrated that despite the sharp difference in their inclusion evolution, composite inclusions with a magnesium aluminate spinel (MAS) core and an outer CaO–Al2O3–MgO layer were formed by all the three addition methods, with the average inclusion size of 1–2 μm. Furthermore, thermodynamic calculation was adopted to reveal the transformation relationship between MAS and calcium aluminate in each of the three addition methods, and clarify the formation and disappearance mechanisms of the intermediate product CaS in the process of Mg–Ca treatment. The thermodynamic calculation results agreed well with the experiment data.
Exploring the Gut Microbiota and Cardiovascular Disease
Authors: Murphy Kiera , O’Donovan Aoife N. , Caplice Noel M. , Ross R. Paul , Stanton Catherine
Published: July 2021

Cardiovascular disease (CVD) has been classified as one of the leading causes of morbidity and mortality worldwide. CVD risk factors include smoking, hypertension, dyslipidaemia, obesity, inflammation and diabetes. The gut microbiota can influence human health through multiple interactions and community changes are associated with the development and progression of numerous disease states, including CVD. The gut microbiota are involved in the production of several metabolites, such as short-chain fatty acids (SCFAs), bile acids and trimethylamine-N-oxide (TMAO). These products of microbial metabolism are important modulatory factors and have been associated with an increased risk of CVD. Due to its association with CVD development, the gut microbiota has emerged as a target for therapeutic approaches. In this review, we summarise the current knowledge on the role of the gut microbiome in CVD development, and associated microbial communities, functions, and metabolic profiles. We also discuss CVD therapeutic interventions that target the gut microbiota such as probiotics and faecal microbiota transplantation.
Metabolomic Profile in Venous Thromboembolism (VTE)
Authors: Franczyk Beata , Gluba-Brzózka Anna , Ławiński Janusz , Rysz-Górzyńska Magdalena , Rysz Jacek
Published: July 2021

Venous thromboembolism (VTE) is a condition comprising deep venous thrombosis (DVT) and pulmonary embolism (PE). The prevalence of this disease is constantly increasing and it is also a chief reason for morbidity. Therefore, the primary prevention of VTE remains a highly important public health issue. At present, its diagnosis generally relies on subjective clinical examination and ultrasound imaging. D-dimer is also used as a biomarker, but it is considered to be poorly specific and only moderately sensitive. There are also no reliable methods that could accurately guide the type of treatment and potentially identify patients who may benefit from more aggressive therapies without the risk of bleeding. The application of metabolomics profiling in the area of vascular diseases may become a turning point in early diagnosis and patient management. Among the most described metabolites possibly related to VTE are carnitine species, glucose, phenylalanine, 3-hydroxybutarate, lactic acid, tryptophan and some monounsaturated and polyunsaturated fatty acids. The cell response to acute PE was suggested to involve the uncoupling between glycolysis and oxidative phosphorylation. Despite technological advancement in the identification of metabolites and their alteration in thrombosis, we still do not understand the mechanisms and pathways responsible for the occurrence of observed alterations.
Antiretroviral Therapy Dampens Mucosal CD4+ T Lamina Propria Lymphocytes Immune Activation in Long-Term Treated People Living with HIV-1
Authors: Lazzaro Alessandro , Innocenti Giuseppe Pietro , Santinelli Letizia , Pinacchio Claudia , De Girolamo Gabriella , Vassalini Paolo , Fanello Gianfranco , Mastroianni Claudio Maria , Ceccarelli Giancarlo , d’Ettorre Gabriella
Published: July 2021

HIV infection is characterized by a severe deterioration of an immune cell-mediated response due to a progressive loss of CD4+ T cells from gastrointestinal tract, with a preferential loss of IL-17 producing Th cells (Th17), a specific CD4+ T cells subset specialized in maintaining mucosal integrity and antimicrobial inflammatory responses. To address the effectiveness of antiretroviral therapy (ART) in reducing chronic immunological dysfunction and immune activation of intestinal mucosa, we conducted a cross-sectional observational study comparing total IFN-γ-expressing (Th1) and IL-17-expressing (Th17) frequencies of CD4+ T lamina propria lymphocytes (LPLs) and their immune activation status between 11 male ART-naïve and 11 male long-term ART-treated people living with HIV-1 (PLWH) who underwent colonoscopy and retrograde ileoscopy for biopsies collection. Flow cytometry for surface and intracellular staining was performed. Long-term ART-treated PLWH showed lower levels of CD38+ and/or HLA-DR+ LPLs compared to ART-naïve PLWH. Frequencies of Th1 and Th17 LPLs did not differ between the two groups. Despite ART failing to restore the Th1 and Th17 levels within the gut mucosa, it is effective in increasing overall CD4+ T LPLs frequencies and reducing mucosal immune activation.
Ceria Particles as Efficient Dopant in the Electrodeposition of Zn-Co-CeO2 Composite Coatings with Enhanced Corrosion Resistance: The Effect of Current Density and Particle Concentration
Authors: Riđošić Marija , Bučko Mihael , Salicio-Paz Asier , García-Lecina Eva , Živković Ljiljana S. , Bajat Jelena B.
Published: July 2021

Novel Zn-Co-CeO2 protective composite coatings were deposited successfully from chloride plating solutions. Two different types of ceria sources were used and compared: commercial ceria powder and home-made ceria sol. Electrodeposition was performed by a direct current in the range of 1–8 A dm−2. Two different agitation modes were used and compared, magnetic stirring and ultrasound-assisted stirring (US). The influence of magnetic stirring on the stability of the related plating baths was evaluated via a dynamic scattering method. The results pointed to better stability of the prepared ceria sol. The morphology of the composite coatings was examined by scanning electron microscopy (SEM), and particle content was determined by energy-dispersive X-ray spectroscopy (EDS). The results showed that the increase in the deposition current density was not beneficial to the coating morphology and particle content. The corrosion behavior of the Zn-Co-CeO2 composite coatings was analyzed and compared by electrochemical impedance spectroscopy and polarization resistance. The ultrasound-assisted electrodeposition at small current densities was favorable for obtaining composite coatings with enhanced corrosion stability. The protection was more effective when US was applied and, additionally, upon utilization of ceria sol as a particle source, which was revealed by higher polarization resistance and greater low-frequency impedance modulus values for sol-derived composite coatings deposited under ultrasound.
Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications
Authors: d’Orlyé Fanny , Trapiella-Alfonso Laura , Lescot Camille , Pinvidic Marie , Doan Bich-Thuy , Varenne Anne
Published: July 2021

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.
Sensitivity of Botrytis cinerea Isolates Complex to Plant Extracts
Authors: Dėnė Lina , Valiuškaitė Alma
Published: July 2021

New agricultural strategies aim to reduce the use of pesticides due to their damage to the environment and humans, and the caused resistance to pathogens. Therefore, alternative sources of antifungal compounds from plants are under investigation lately. Extracts from plants have a wide composition of chemical compounds which may complicate the development of pathogen resistance. Botrytis cinerea, causing grey mould, is an important horticultural and ornamental pathogen, responsible for the relevant yield and quality losses. B. cinerea isolated from a different plant host may differ in the sensitivity to antifungal substances from plants. Assessing the importance of research covering a wide range of pathogens for the rapid development of biopesticides, this study aims to determine the sensitivity of the B. cinerea isolate complex (10 strains) to plant extracts, describe morphological changes caused by the extract treatment, and detect differences between the sensitivity of different plant host isolates. The results showed the highest sensitivity of the B. cinerea isolates complex to cinnamon extract, and the lowest to laurel extract. In contrast, laurel extract caused the most changes of morphological attributes in the isolates. Five B. cinerea isolates from plant hosts of raspberry, cabbage, apple, bell pepper, and rose were grouped statistically according to their sensitivity to laurel extract. Meanwhile, the bell pepper isolate separated from the isolate complex based on its sensitivity to clove extract, and the strawberry and apple isolates based on their sensitivity to cinnamon extract.
Added-Value Chemicals from Lignin Oxidation
Authors: Costa Carina A. Esteves , Vega-Aguilar Carlos A. , Rodrigues Alírio E.
Published: July 2021

Lignin is the second most abundant component, next to cellulose, in lignocellulosic biomass. Large amounts of this polymer are produced annually in the pulp and paper industries as a coproduct from the cooking process—most of it burned as fuel for energy. Strategies regarding lignin valorization have attracted significant attention over the recent decades due to lignin’s aromatic structure. Oxidative depolymerization allows converting lignin into added-value compounds, as phenolic monomers and/or dicarboxylic acids, which could be an excellent alternative to aromatic petrochemicals. However, the major challenge is to enhance the reactivity and selectivity of the lignin structure towards depolymerization and prevent condensation reactions. This review includes a comprehensive overview of the main contributions of lignin valorization through oxidative depolymerization to produce added-value compounds (vanillin and syringaldehyde) that have been developed over the recent decades in the LSRE group. An evaluation of the valuable products obtained from oxidation in an alkaline medium with oxygen of lignins and liquors from different sources and delignification processes is also provided. A review of C4 dicarboxylic acids obtained from lignin oxidation is also included, emphasizing catalytic conversion by O2 or H2O2 oxidation.
Chemical Identification of Specialized Metabolites from Sulla (Hedysarum coronarium L.) Collected in Southern Italy
Authors: Tava Aldo , Biazzi Elisa , Ronga Domenico , Mella Mariella , Doria Filippo , D’Addabbo Trifone , Candido Vincenzo , Avato Pinarosa
Published: July 2021

Sulla (Hedysarum coronarium L.) is a biennal forage legume originated from the Mediterranean basin and used for animal feeding due to its high forage quality and palatability. Several species of Hedysarum have been considered for their nutritional, pharmaceutical, and biological properties, and different applications have been reported, both for human consumption and animal nutrition. Although a systematic investigation of the chemical constituents of Hedysarum spp. has been performed in order to provide chemotaxonomic evidences for the genus and to support the pharmacological application of several species within the genus, few data are available on the chemical constituents of H. coronarium, and only the content of condensed tannins and flavonoids in leaves has been previously reported. In the present paper, results from a detailed chemical analysis of the extracts from the leaves and flowers of H. coronarium grown wild in southern Italy are presented. Identification of the main specialized metabolites within the chemical classes of flavonoids, proanthocyanidins and saponins, is described, including considerations on their content in the two plant organs. Information acquired from this study expands the knowledge on H. coronarium as a source of valuable phytochemicals for different applications in human and animal health and nutrition.
Iron Oxide Nanoparticles as Theranostic Agents in Cancer Immunotherapy
Authors: Canese Rossella , Vurro Federica , Marzola Pasquina
Published: July 2021

Starting from the mid-1990s, several iron oxide nanoparticles (NPs) were developed as MRI contrast agents. Since their sizes fall in the tenths of a nanometer range, after i.v. injection these NPs are preferentially captured by the reticuloendothelial system of the liver. They have therefore been proposed as liver-specific contrast agents. Even though their unfavorable cost/benefit ratio has led to their withdrawal from the market, innovative applications have recently prompted a renewal of interest in these NPs. One important and innovative application is as diagnostic agents in cancer immunotherapy, thanks to their ability to track tumor-associated macrophages (TAMs) in vivo. It is worth noting that iron oxide NPs may also have a therapeutic role, given their ability to alter macrophage polarization. This review is devoted to the most recent advances in applications of iron oxide NPs in tumor diagnosis and therapy. The intrinsic therapeutic effect of these NPs on tumor growth, their capability to alter macrophage polarization and their diagnostic potential are examined. Innovative strategies for NP-based drug delivery in tumors (e.g., magnetic resonance targeting) will also be described. Finally, the review looks at their role as tracers for innovative, and very promising, imaging techniques (magnetic particle imaging-MPI).
Higher Fruit and Vegetable Intake Is Associated with Participation in the Double Up Food Bucks (DUFB) Program
Authors: Atoloye Abiodun T. , Savoie-Roskos Mateja R. , Durward Carrie M.
Published: July 2021

Incentivizing fruit and vegetable (F&V) purchases may help address barriers to healthy eating among populations with low income. In a repeated measures natural experiment study, we examined whether participation in the Double Up Food Bucks (DUFB) program increased F&V consumption among Supplemental Nutrition Assistance Program (SNAP) recipients. Two hundred and twelve participants recruited at baseline through telephone calls were informed about the availability of DUFB at their local farmers’ market (FM). F&V consumption frequency and DUFB use were obtained at baseline, mid FM, and end of FM season approximately 5 months later. Participants (N = 212) were primarily white (76.4%) women (77.3%) with an average age of 43.5 years. Only 34 participants opted to use the DUFB program. A linear mixed model showed a significant main effect of DUFB use (p = 0.001) and of time (p = 0.002), with a decrease in F&V intake over time. Compared to non-users, DUFB users had a significantly higher F&V consumption at baseline and midpoint (p = 0.02 and p = 0.02, respectively). F&V consumption was associated with participation in the DUFB program and higher F&V consumption frequency was observed prior to program use among program participants. Future interventions that specifically target SNAP recipients with low F&V intake to use the DUFB program are needed.
Testing and Prescribing Vitamin B12 in Swiss General Practice: A Survey among Physicians
Authors: Bardheci Katarina , Jäger Levy , Risch Lorenz , Rosemann Thomas , Burgstaller Jakob M. , Markun Stefan
Published: July 2021

Testing and prescribing vitamin B12 (also known as cobalamin) is increasing in Switzerland but substantial variation among general practitioners (GPs) with respect to testing has been noted. In this study, we aimed at exploring GPs’ mindsets regarding vitamin B12 testing and prescribing. A cross-sectional study was conducted using an online survey distributed by e-mail to Swiss GPs. The questionnaire explored mindsets related to testing and prescribing vitamin B12 in specific clinical situations, as well as testing and prescribing strategies. The questionnaire was sent to 876 GPs and 390 GPs responded (44.5%). The most controversial domains for testing and prescribing vitamin B12 were idiopathic fatigue (57.4% and 43.4% of GPs agreed, respectively) and depressive symptoms (53.0% and 35.4% of GPs agreed, respectively). There was substantial variation among GPs with regard to testing strategies (89.5% of GPS used a serum cobalamin test, 71.3% of GPS used holotranscobalamin, and 27.6% of GPs used homocysteine or methylmalonic acid). Intramuscular injection was the predominantly prescribed route of application (median of 87.5% of the prescriptions). In this study, we focus on discordant mindsets that can be specifically targeted by using educational interventions, and research questions that still need answering specifically about the effectiveness of vitamin B12 for idiopathic fatigue.
Dietary Fat Chain Length, Saturation, and PUFA Source Acutely Affect Diet-Induced Thermogenesis but Not Satiety in Adults in a Randomized, Crossover Trial
Authors: Rust Bret M. , Raatz Susan K. , Casperson Shanon L. , Duke Sara E. , Picklo Matthew J.
Published: July 2021

Structural differences in dietary fatty acids modify their rate of oxidation and effect on satiety, endpoints that may influence the development of obesity. This study tests the hypothesis that meals containing fat sources with elevated unsaturated fats will result in greater postprandial energy expenditure, fat oxidation, and satiety than meals containing fats with greater saturation. In a randomized, 5-way crossover design, healthy men and women (n = 23; age: 25.7 ± 6.6 years; BMI: 27.7 ± 3.8 kg/m2) consumed liquid meals containing 30 g of fat from heavy cream (HC), olive oil (OO), sunflower oil (SFO), flaxseed oil (FSO), and fish oil (FO). Energy expenditure and diet-induced thermogenesis (DIT) were determined by metabolic rate over a 240 min postprandial period. Serum concentrations of ghrelin, glucose, insulin, and triacylglycerol (TAG) were assessed. DIT induced by SFO was 5% lower than HC and FO (p = 0.04). Energy expenditure and substrate oxidation did not differ between fat sources. Postprandial TAG concentrations were significantly affected by fat source (p = 0.0001). Varying fat sources by the degree of saturation and PUFA type modified DIT but not satiety responses in normal to obese adult men and women.
Effects of Cranberry Juice Supplementation on Cardiovascular Disease Risk Factors in Adults with Elevated Blood Pressure: A Randomized Controlled Trial
Authors: Richter Chesney K. , Skulas-Ray Ann C. , Gaugler Trent L. , Meily Stacey , Petersen Kristina S. , Kris-Etherton Penny M.
Published: July 2021

Emerging cardiovascular disease (CVD) risk factors, including central vascular function and HDL efflux, may be modifiable with food-based interventions such as cranberry juice. A randomized, placebo-controlled, crossover trial was conducted in middle-aged adults with overweight/obesity (n = 40; mean BMI: 28.7 ± 0.8 kg/m2; mean age: 47 ± 2 years) and elevated brachial blood pressure (mean systolic/diastolic BP: 124 ± 2/81 ± 1 mm Hg). Study participants consumed 500 mL/d of cranberry juice (~16 fl oz; 27% cranberry juice) or a matched placebo juice in a randomized order (8-week supplementation periods; 8-week compliance break), with blood samples and vascular measurements obtained at study entry and following each supplementation period. There was no significant treatment effect of cranberry juice supplementation on the primary endpoint of central systolic blood pressure or central or brachial diastolic pressure. Cranberry juice significantly reduced 24-h diastolic ambulatory BP by ~2 mm Hg compared to the placebo (p = 0.05) during daytime hours. Cranberry juice supplementation did not alter LDL-C but significantly changed the composition of the lipoprotein profile compared to the placebo, increasing the concentration of large LDL-C particles (+29.5 vs. −6.7 nmol/L; p = 0.02) and LDL size (+0.073 vs. −0.068 nm; p = 0.001). There was no effect of treatment on ex vivo HDL efflux in the total population, but exploratory subgroup analyses identified an interaction between BMI and global HDL efflux (p = 0.02), with greater effect of cranberry juice in participants who were overweight. Exploratory analyses indicate that baseline C-reactive protein (CRP) values may moderate treatment effects. In this population of adults with elevated blood pressure, cranberry juice supplementation had no significant effect on central systolic blood pressure but did have modest effects on 24-h diastolic ambulatory BP and the lipoprotein profile. Future studies are needed to verify these findings and the results of our exploratory analyses related to baseline health moderators.
High BMI Predicts Attention to Less Healthy Product Sets: Can a Prompt Lead to Consideration of Healthier Sets of Products?
Authors: Gustafson Christopher R. , Arslain Kristina , Rose Devin J.
Published: July 2021

While the food environment has been implicated in diet-related health disparities, individuals’ ability to shape the food environment by limiting attention to a subset of products has not been studied. We examine the relationship between BMI category and consideration set—the products the individual considers before making a final choice—in an online hypothetical shopping experiment. Specifically, we focus on the healthiness of the consideration set the individual selected. Secondly, we examined the interaction of a health prompt (versus a no-prompt control) with BMI category on the healthiness of the consideration set. We used linear probability models to document the relationship between weight status and consideration set, between prompt and consideration set, and the effect of the interaction between prompt and weight status on consideration set. We found that (1) obese individuals are 10% less likely to shop from a consideration set that includes the healthy options, (2) viewing the prompt increased the probability of choosing a healthy consideration set by 9%, and (3) exposure to the prompt affected individuals in different BMI categories equally. While obese individuals are more likely to ignore healthier product options, a health-focused prompt increases consideration of healthy options across all BMI categories.
Mediterranean Diet and Mortality in People with Cardiovascular Disease: A Meta-Analysis of Prospective Cohort Studies
Authors: Tang Chengyao , Wang Xiaowen , Qin Li-Qiang , Dong Jia-Yi
Published: July 2021

The association of the Mediterranean diet (MD) with mortality among people with a history of cardiovascular disease (CVD) has not been systematically examined. Hereby, our objective was to investigate the association of MD with all-cause and cardiovascular mortality in people with a history of CVD. We searched five electronic databases including Embase, PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials to screen eligible studies published before 31 August 2020. A random-effect model was used to examine the association of a 2-unit increment in MD score with the risk of all-cause and cardiovascular mortality. We conducted sensitivity and subgroup analyses and examined potential publication bias by Egger’s and Begg’s tests. Seven cohort studies (eight datasets) with a total of 37,879 participants who had a history of CVD were eligible for the main analysis. The pooled hazard ratios were 0.85 (95% CIs: 0.78–0.93; n = 8) for all-cause mortality and 0.91 (95% CIs; 0.82–1.01; n = 4) for cardiovascular mortality for each 2-unit increment in a score of adherence to MD. Subgroup analyses for all-cause mortality showed that the association appeared relatively stronger in Mediterranean areas (HR = 0.76 [0.69–0.83]) than non-Mediterranean areas (HR = 0.95 [0.93–0.98]) and in studies with a shorter duration (HR = 0.75 [0.66–0.84] for <7 years vs. HR = 0.94 [0.91–0.98] for ≥7 years). No evidence of publication bias was observed. The present meta-analysis of prospective cohort studies provided evidence that adherence to MD improved survival in people with a history of CVD.
Does Sodium Intake Induce Systemic Inflammatory Response? A Systematic Review and Meta-Analysis of Randomized Studies in Humans
Authors: Basdeki Eirini , Kollias Anastasios , Mitrou Panagiota , Tsirimiagkou Christiana , Georgakis Marios , Chatzigeorgiou Antonios , Argyris Antonios , Karatzi Kalliopi , Manios Yannis , Sfikakis Petros , Protogerou Athanase
Published: July 2021

Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP (n = 5 studies), TNF-a (n = 4 studies) and IL-6 (n = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(−0.3, 0.4) mg/L; TNF-a −0.7(−5.0, 3.6) pg/mL; IL-6 −1.1(−3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, “normal” and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.
Ecological Study of Fractures in Paediatric Melanesian Communities with Varying Endemic Environmental Fluoride Exposure
Authors: Elizabeth Webb , Elmansouri Ahmad , Ross Rebecca , Clynes Michael , Tangis Jenny , Stewart Carol , Dennison Elaine M.
Published: July 2021

Introduction: Osteoporotic fracture is a major public health burden worldwide, causing significant mortality and morbidity. Studies that have reported bone health in areas of high endemic fluorosis have commonly reported adverse skeletal, as well as dental effects. Vanuatu, sited in the Pacific, and never previously studied with regard to bone health, has six continuous degassing volcanoes on separate islands, resulting in a natural experiment for an ecological study of relationships between naturally occurring fluoride exposure and fracture incidence in paediatric populations. Methods: This ecological study recruited 1026 lifetime residents of the rural Vanuatu islands. A short questionnaire was administered detailing gender, age, and residential history. Participants were asked if they had broken a bone and, if so, were asked to mark its location on a questionnaire manikin. Dental fluorosis was assessed using Dean’s index. Community drinking-water samples were sampled for fluoride concentration. Results: The measured water fluoride concentration and recorded dental fluorosis displayed expected gradients from Aneityum (low) to Ambrym (high) (p < 0.001). The age of participants studied varied from 7.8 (SD 1.2) in Aneityum to 10.6 (3.7) in Lamap/Uliveo. The highest self-reported fracture rates were recorded in the area with medium fluoride levels (Lamap/Uliveo), where 14.9% of boys and 15.6% of girls sampled reported a fracture. In Ambrym, where the mean age of participants was similar, corresponding fracture rates were 4.5% and 2.6%. (p value for differences all < 0.05). Conclusions: Reports of fractures were common in children living in Vanuatu, but demonstrably higher in Lamap, the region with medium fluoride concentrations, rather than Ambrym which had very high rates of naturally occurring fluoride levels. Longer term studies that report validated fracture after peak bone mass acquisition are required.
A Case Report of Chronic Stress in Honey Bee Colonies Induced by Pathogens and Acaricide Residues
Authors: Alonso-Prados Elena , González-Porto Amelia-Virginia , Bernal José Luis , Bernal José , Martín-Hernández Raquel , Higes Mariano
Published: July 2021

In this case report, we analyze the possible causes of the poor health status of a professional Apis mellifera iberiensis apiary located in Gajanejos (Guadalajara, Spain). Several factors that potentially favor colony collapse were identified, including Nosema ceranae infection, alone or in combination with other factors (e.g., BQCV and DWV infection), and the accumulation of acaricides commonly used to control Varroa destructor in the beebread (coumaphos and tau-fluvalinate). Based on the levels of residues, the average toxic unit estimated for the apiary suggests a possible increase in vulnerability to infection by N. ceranae due to the presence of high levels of acaricides and the unusual climatic conditions of the year of the collapse event. These data highlight the importance of evaluating these factors in future monitoring programs, as well as the need to adopt adequate preventive measures as part of national and international welfare programs aimed at guaranteeing the health and fitness of bees.
Immunodominant Cytomegalovirus Epitopes Suppress Subdominant Epitopes in the Generation of High-Avidity CD8 T Cells
Authors: Freitag Kirsten , Hamdan Sara , Reddehase Matthias J. , Holtappels Rafaela
Published: July 2021

CD8+ T-cell responses to pathogens are directed against infected cells that present pathogen-encoded peptides on MHC class-I molecules. Although natural responses are polyclonal, the spectrum of peptides that qualify for epitopes is remarkably small even for pathogens with high coding capacity. Among those few that are successful at all, a hierarchy exists in the magnitude of the response that they elicit in terms of numbers of CD8+ T cells generated. This led to a classification into immunodominant and non-immunodominant or subordinate epitopes, IDEs and non-IDEs, respectively. IDEs are favored in the design of vaccines and are chosen for CD8+ T-cell immunotherapy. Using murine cytomegalovirus as a model, we provide evidence to conclude that epitope hierarchy reflects competition on the level of antigen recognition. Notably, high-avidity cells specific for non-IDEs were found to expand only when IDEs were deleted. This may be a host’s back-up strategy to avoid viral immune escape through antigenic drift caused by IDE mutations. Importantly, our results are relevant for the design of vaccines based on cytomegaloviruses as vectors to generate high-avidity CD8+ T-cell memory specific for unrelated pathogens or tumors. We propose the deletion of vector-encoded IDEs to avoid the suppression of epitopes of the vaccine target.
In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management
Authors: Gomes Diana , Silvestre Samuel , Duarte Ana Paula , Venuti Aldo , Soares Christiane P. , Passarinha Luís , Sousa Ângela
Published: July 2021

Cervical cancer (CC) is the fourth most common pathology in women worldwide and presents a high impact in developing countries due to limited financial resources as well as difficulties in monitoring and access to health services. Human papillomavirus (HPV) is the leading cause of CC, and despite the approval of prophylactic vaccines, there is no effective treatment for patients with pre-existing infections or HPV-induced carcinomas. High-risk (HR) HPV E6 and E7 oncoproteins are considered biomarkers in CC progression. Since the E6 structure was resolved, it has been one of the most studied targets to develop novel and specific therapeutics to treat/manage CC. Therefore, several small molecules (plant-derived or synthetic compounds) have been reported as blockers/inhibitors of E6 oncoprotein action, and computational-aided methods have been of high relevance in their discovery and development. In silico approaches have become a powerful tool for reducing the time and cost of the drug development process. Thus, this review will depict small molecules that are already being explored as HR HPV E6 protein blockers and in silico approaches to the design of novel therapeutics for managing CC. Besides, future perspectives in CC therapy will be briefly discussed.