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17 pages, 1048 KB  
Article
Development of a Tool to Assess the Implementation and Perception of the Value-Based Healthcare Model: Our Results
by Egidio de Mattia, Dorine van Staalduinen, Ilaria Valentini, Paul B van der Nat and Antonio Giulio de Belvis
Healthcare 2025, 13(22), 2849; https://doi.org/10.3390/healthcare13222849 - 10 Nov 2025
Viewed by 773
Abstract
Background/Objectives: A successful implementation of VBHC requires significant transformations, spanning from structural adjustments to a fundamental shift in organizational culture. However, organizations often adopt VBHC principles piecemeal, while managers overlook diverse staff reactions and their leadership role. To address these challenges, we developed [...] Read more.
Background/Objectives: A successful implementation of VBHC requires significant transformations, spanning from structural adjustments to a fundamental shift in organizational culture. However, organizations often adopt VBHC principles piecemeal, while managers overlook diverse staff reactions and their leadership role. To address these challenges, we developed and validated a multi-source assessment tool for use by organizations during their transition to VBHC to determine whether they are progressing effectively in both the dimensions. Method: To develop the first version of the tool, a multidisciplinary group translated strategies identified in a previous scoping review into questionnaire items through structured sessions. To validate it, a two round Delphi analysis was conducted. Experts in VBHC, management, health economy and clinical/researcher were contacted to ask for their participation. Consensus was established based on the following criteria: a median (Mdn) score of ≥4, an interquartile range (IQR) of ≤1.5 or ≤2, and a frequency of ratings in the range [4–5] ≥ 70%. Results: A total of 54 experts were invited to participate in the Delphi survey. The first round received 25 responses, while the second round had 23 responses. The final version of the assessment tool consists of 30 questions divided into two macro-areas: the Value Agenda Section and the Change Management Section. All items achieved a minimum frequency of ratings > 80% during both the rounds. Conclusion: By comparing the perspectives of managers and clinicians, the resulting tool enables organizations to assess the adoption of the Value Agenda component, as well as the change management strategies supporting its implementation. Full article
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14 pages, 2670 KB  
Article
Genomic Characterization of Cryptococcus neoformans Isolated from Zebra Dove Excreta in Songkhla, Thailand
by Saowakon Indoung, Sanicha Chumtong, Sakaoporn Prachantasena, Ratchakul Wiriyaprom, Komwit Surachat, Sarunyou Chusri, Rattanaruji Pomwised and Ruttayaporn Ngasaman
Vet. Sci. 2025, 12(9), 827; https://doi.org/10.3390/vetsci12090827 - 28 Aug 2025
Viewed by 1332
Abstract
The research aimed to study the genome of Cryptococcus neoformans isolated from bird excreta. Thirteen isolates were cultured, colony stained, and underwent biochemical testing confirmation by nested polymerase chain reaction using ITS1-ITS4 and CN4-CN5 primers, respectively. Antifungal susceptibility testing and whole-genomic sequencing were [...] Read more.
The research aimed to study the genome of Cryptococcus neoformans isolated from bird excreta. Thirteen isolates were cultured, colony stained, and underwent biochemical testing confirmation by nested polymerase chain reaction using ITS1-ITS4 and CN4-CN5 primers, respectively. Antifungal susceptibility testing and whole-genomic sequencing were analyzed. The results determined that all isolates were susceptible to amphotericin B (100%), fluconazole, and itraconazole (92.3%). One isolate (DOP3) showed resistance to fluconazole and itraconazole (MIC >64 and >8 µg/mL, respectively). A phylogenetic tree showed the identity of C. neoformans (serotype A). The genome of resistant (DOP3) and non-resistant isolates (DOP3.1) had 14 chromosomes. DOP3 consisted of 38 candidate antifungal resistance genes, which were the most active against azoles (14). The annotated genes in the azole group mostly were in the ATP-binding cassette transporter transmembrane superfamily. Resistance genes against FCZ were in the transcription factors (HAP2, HAP5), zinc finger (NRG1), cytochrome P450 (ERG11), and Myb-like DNA-binding domain (REB1). The most frequent resistance genes against ITZ were cytochrome P450 (ERG5 and ERG11) and a transcription factor (HAP5). DOP3.1 also consisted of 26 candidate resistance genes against azoles. Resistance genes against the azole group belong to the ABC transporter transmembrane superfamily. Resistance genes against FCZ belong to cytochrome P450 (ERG11), the zinc finger (NRG1), and the CCAAT binding transcription factor (HAP2). Resistance genes belonging to cytochrome P450 (ERG5) were found against ITZ. This research provides the first report of C. neoformans (serotype A) in zebra dove excreta, drug susceptibility to a resistant strain, and identification of resistance genes. Farm sanitation should be strictly applied, and immunocompetent people should avoid contact with zebra dove excreta. Full article
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17 pages, 3602 KB  
Article
Natural Low-Eutectic Solvent Co-Culture-Assisted Whole-Cell Catalyzed Synthesis of Ethyl (R)-4-Chloro-3-Hydroxybutyrate
by Yanni Wang, Bo Liu, Yanmei Dai, Zijuan Tao, Lan Tang and Zhimin Ou
Molecules 2025, 30(13), 2869; https://doi.org/10.3390/molecules30132869 - 6 Jul 2025
Viewed by 820
Abstract
In this study, CGMCC NO:28566, a strain that can efficiently convert Ethyl 4-chloroacetoacetate(COBE) to (R)-4-chloro-3-hydroxybutyrate((R)-CHBE), was screened by soil-sieving bacteria. In order to improve the transformation effect of the strain, the natural low-eutectic solvent (NADES), which can alter the [...] Read more.
In this study, CGMCC NO:28566, a strain that can efficiently convert Ethyl 4-chloroacetoacetate(COBE) to (R)-4-chloro-3-hydroxybutyrate((R)-CHBE), was screened by soil-sieving bacteria. In order to improve the transformation effect of the strain, the natural low-eutectic solvent (NADES), which can alter the cell permeability, was utilized for assisted catalysis, and a better catalytic effect was achieved. This study was carried out using a co-culture of strains with NADES and secondary addition of NADES on the basis of co-culture, and 10 NADESs were screened at the same time. The co-catalytic effect of 0.5% (w/v) choline chloride: urea (1:2) (ChCl:U (1:2)) was found to be the most significant, with a yield of (R)-CHBE reaching 89.1%, which was 58.2% higher than that of the control group, with a 99% ee value. Furthermore, the catalytic results demonstrated that the co-culture of the strain with NADES during fermentation yielded superior outcomes to the secondary addition of NADES during the reaction buffer. Furthermore, the catalytic effect of ChCl:U (1:2) was demonstrated to be superior to that of its individual components or single-component blends, due to its distinctive valence bonding advantage. The results indicate that the addition of 0.5% (w/v) ChCl:U (1:2) during the co-culture process has the effect of improving cell permeability to a certain extent, thereby increasing the contact between the substrate and the enzyme during the whole-cell catalytic reactions. Full article
(This article belongs to the Special Issue Current Development of Asymmetric Catalysis and Synthesis)
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26 pages, 4870 KB  
Article
Incorporation of Zinc Oxide Nanoparticles Biosynthesized from Epimedium brevicornum Maxim. into PCL Nanofibers to Enhance Osteogenic Differentiation of Periodontal Ligament Stem Cells
by Kuei-Ping Hsieh, Parichart Naruphontjirakul, Jen-Hao Chen, Chih-Sheng Ko, Chi-Wei Lin and Wen-Ta Su
Materials 2025, 18(10), 2295; https://doi.org/10.3390/ma18102295 - 15 May 2025
Cited by 1 | Viewed by 1046
Abstract
The optimal parameters for the microwave-assisted extraction of Epimedium brevicornum Maxim. were determined by using response surface methodology (RSM), increasing the extraction of flavonoids by 1.79 times. The resulting extract facilitated the green synthesis of zinc oxide nanoparticles (ZnONPs) with a wurtzite structure [...] Read more.
The optimal parameters for the microwave-assisted extraction of Epimedium brevicornum Maxim. were determined by using response surface methodology (RSM), increasing the extraction of flavonoids by 1.79 times. The resulting extract facilitated the green synthesis of zinc oxide nanoparticles (ZnONPs) with a wurtzite structure through a reaction with zinc nitrate. These ZnONPs were then incorporated into polycaprolactone (PCL) by using an electrospinning technique to produce nanofibers. The incorporation of ZnONPs resulted in an increase in Young’s modulus, biodegradation rate, and swelling ratio while decreasing the diameter and water contact angle of the nanofibers, thereby improving the hydrophilicity of PCL. ZnO demonstrates excellent biocompatibility with periodontal ligament stem cells (PDLSCs), increasing cell proliferation and enhancing alkaline phosphatase activity by 56.9% (p < 0.05). Additionally, mineralization deposition increased by 119% (p < 0.01) in the presence of 1% ZnO and showed a concentration-dependent response. After inducing PDLSC cultures with PCL–1% ZnO for 21 days, the protein expression levels of Runx2 and OCN increased by 50% (p < 0.05) and 30% (p < 0.001), respectively. Additionally, Col-1, Runx2, BSP, and OCN gene expression levels increased by 2.18, 1.88, 1.8, and 1.7 times, respectively. This study confirms that biosynthesized ZnONPs improve the physical properties of PCL nanofibers and effectively induce the osteogenic differentiation of PDLSCs. Full article
(This article belongs to the Special Issue Diverse Nanomaterials Applied in Bio- and Electrochemical Sensing)
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19 pages, 3426 KB  
Article
PLA/PMMA Reactive Blending in the Presence of MgO as an Exchange Reaction Catalyst
by Masoud Komeijani, Naeimeh Bahri-Laleh, Zohreh Mirjafary, Massimo Christian D’Alterio, Morteza Rouhani, Hossein Sakhaeinia, Amin Hedayati Moghaddam, Seyed Amin Mirmohammadi and Albert Poater
Polymers 2025, 17(7), 845; https://doi.org/10.3390/polym17070845 - 21 Mar 2025
Cited by 5 | Viewed by 1259
Abstract
To address the limitations of poly (lactic acid) (PLA), it was blended with poly (methyl methacrylate) (PMMA) as a toughening component, using MgO nanoparticles (NPs, 0.075–0.15 wt%) as a catalyst. SEM pictures confirmed the good miscibility of the blends. Mechanical tests showed a [...] Read more.
To address the limitations of poly (lactic acid) (PLA), it was blended with poly (methyl methacrylate) (PMMA) as a toughening component, using MgO nanoparticles (NPs, 0.075–0.15 wt%) as a catalyst. SEM pictures confirmed the good miscibility of the blends. Mechanical tests showed a slight decrease in elastic modulus and tensile strength for the PLA/PMMA125 sample containing 0.125% MgO. Yet, elongation at break rose by over 60% and impact strength increased by over 400% compared to pure PLA. Also, MgO facilitated the shifting of the glass transition temperature (Tg) of both polymers in DSC curves. Additionally, the absence of cold crystallization in PLA, coupled with reductions in its melting temperature (Tm) and crystallinity, were identified as critical factors contributing to improved miscibility within the reactive blend. Melt flow index (MFI) evaluation indicated a decrease in viscosity, while water contact angle measurements revealed an increase in polar groups on the surfaces of the MgO-containing samples. X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses confirmed the effective distribution and dispersion of NPs throughout the blend, along with a significant decrease in crystallinity. Moreover, DFT calculations were performed to better understand the role of MgO in the reaction. The findings offered key insights into the reaction mechanism, confirming that MgO plays a crucial role in facilitating the transesterification between PLA and PMMA. These findings underscore the enhanced performance of exchange reactions between the active groups of both polymers in the presence of MgO, leading to the formation of PLA-PMMA copolymers with superior miscibility and mechanical properties. Finally, a cell culture assay confirmed the blend’s non-toxicity, showing its versatile potential. Full article
(This article belongs to the Section Polymer Chemistry)
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17 pages, 1615 KB  
Article
Serum Levels of IL-6 and TNF-α, Salivary Morning Cortisol and Intensity of Psychological Stress in Patients with Allergic Contact Hand Dermatitis and Healthy Subjects
by Nives Pondeljak, Liborija Lugović-Mihić, Blaženka Ladika Davidović, Dalibor Karlović, Milena Hanžek and Marijana Neuberg
Life 2025, 15(3), 351; https://doi.org/10.3390/life15030351 - 24 Feb 2025
Cited by 3 | Viewed by 3406
Abstract
Introduction: Allergic contact dermatitis (ACD) is a form of late hypersensitivity reaction of skin contact with allergens. As an inflammatory skin disease, ACD has a negative impact on the quality of life and there is a need to elucidate the etiopathogenetic factors of [...] Read more.
Introduction: Allergic contact dermatitis (ACD) is a form of late hypersensitivity reaction of skin contact with allergens. As an inflammatory skin disease, ACD has a negative impact on the quality of life and there is a need to elucidate the etiopathogenetic factors of the disease, whereby using the psychoneuroimmunological (PNI) approach can be helpful. Psychological stress (PS), as a component of PNI, leads to aggravation of the contact hypersensitivity reaction. In response to the perception of PS, cortisol secretion is enhanced by activation of the hypothalamic–pituitary–adrenal (HPA) axis. Furthermore, the pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) play a role in activating the HPA axis as well as initiating and maintaining inflammatory responses. Recent studies show that IL-6, IL-1, and TNF-α values are increased in the serum of patients with contact dermatitis, as well as in keratinocyte cell culture. Methods: The study examined the association of PNI factors (serum IL-6 and TNF-α, stress intensity with a Perceived Stress Scale (PSS) questionnaire, quality of life of dermatology patients with a Dermatology Life Quality Index (DLQI)) with the disease severity evaluated using the Hand Eczema Extent Score (HEES) and the duration of disease in hand ACD patients. Results: Patients with hand ACD had higher PSS (p = 0.001) than healthy people, with no difference in IL-6 and TNF-α. Higher DLQI was associated with higher HEES and PSS (p = 0.002 and p < 0.001) and these were the only predictors of DLQI. The duration of the disease was not related to the investigated factors. Conclusion: This study is the first so far, to our knowledge, in which a detailed analysis of PNI factors in patients with hand ACD was conducted. The results show that patients with ACD have higher PS intensity, which can chronically indicate changes in the balance of the HPA axis and indirectly affect the quality of life and disease severity of this disease. The results of the research provide more knowledge about hand ACD and contribute to and emphasize the importance of a multidisciplinary approach to treatment, thus improving the quality of life of these patients. Full article
(This article belongs to the Special Issue Innovative Approaches in Dermatological Therapies and Diagnostics)
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16 pages, 414 KB  
Article
The Impact of the Assyrian Conquests on Judahite Society: The Social, Psychological, and Physical Contexts for Religious Development
by Avraham Faust
Religions 2025, 16(2), 120; https://doi.org/10.3390/rel16020120 - 23 Jan 2025
Viewed by 4175
Abstract
Various scholars have noted Mesopotamian impact on various aspects of Israelite religious beliefs and practices and extrapolated from these on the broader nature of the relations between the regions. Indeed, no society is an island, and influences are inevitable, especially when a small, [...] Read more.
Various scholars have noted Mesopotamian impact on various aspects of Israelite religious beliefs and practices and extrapolated from these on the broader nature of the relations between the regions. Indeed, no society is an island, and influences are inevitable, especially when a small, peripheral society is in contact with a powerful center. Still, insufficient attention has been paid to the social and cultural contexts of the interaction, and studies have often extrapolated from examples that are exceptional. A systematic examination of the cultural and social reactions in Judah to the intensifying interaction with Assyria reveals that avoidance, subversion, and resistance were far more prevalent than emulation. The large-scale death and deportations that accompanied the destruction of sites and regions by the Assyrian armies in the last third of the 8th century (mostly outside Judah) resulted in an understanding that nothing was secure anymore, that complete kinship groups could be annihilated overnight, and that long-held traditions could simply vanish. This gave rise to a mentality of “life in the shadow of the bomb”, which explains many subsequent developments in Judah, providing the context for various religious changes. Full article
(This article belongs to the Special Issue The Bible and Ancient Mesopotamia)
11 pages, 474 KB  
Article
Chinese College Students’ Stigmatization towards People with Mental Illness: Familiarity, Perceived Dangerousness, Fear, and Social Distance
by Xu-Hong Li, Yin-Ling Irene Wong, Qinglu Wu, Mao-Sheng Ran and Tian-Ming Zhang
Healthcare 2024, 12(17), 1715; https://doi.org/10.3390/healthcare12171715 - 27 Aug 2024
Cited by 4 | Viewed by 2060
Abstract
Background: Attribution models have been examined in Western countries. However, little is known about the applicability of the attitude–emotion–behavior model within Chinese culture. This study aimed to examine the association between familiarity, perceived dangerousness, fear, and social distance towards persons with mental illness [...] Read more.
Background: Attribution models have been examined in Western countries. However, little is known about the applicability of the attitude–emotion–behavior model within Chinese culture. This study aimed to examine the association between familiarity, perceived dangerousness, fear, and social distance towards persons with mental illness (PMI) in the Chinese context. Methods: An online cross-sectional survey was conducted from October to November 2022 in mainland China. A total of 1493 college students completed a questionnaire evaluating familiarity, perception of dangerousness, fear, and social distance regarding PMI. Path analysis was employed to validate the model proposed in this study. Results: Participants expressed moderate to high levels of stigma towards PMI. Familiarity was negatively associated with social distance (p < 0.01). Participants who perceived PMI as dangerous were more prone to exhibit a reaction of fear (p < 0.001), consequently leading to social distance (p < 0.01). However, the mediating effect of perceived dangerousness and fear on the relationship between familiarity and social distance was not significant (p > 0.05). Conclusions: The results of this study provide support for Corrigan’s attributional model of stigma in the Chinese context. Contact-based interventions for stigma reduction should emphasize multiple elements of contact, including the quality of contact, rather than familiarity. Full article
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28 pages, 6536 KB  
Article
The Condition of Contemporary Murals in Sun-Exposed Urban Environments: A Model Study Based on Spray-Painted Mock-Ups and Simulated Light Ageing
by Varvara Marazioti, Antonios M. Douvas, Evangelia C. Vouvoudi, Dimitrios Bikiaris, Kyriaki Papadokostaki, Dimitrios Nioras, Evangelos Gogolides, Spyros Orfanoudakis, Thomas Stergiopoulos, Stamatios Boyatzis and Yorgos Facorellis
Heritage 2024, 7(8), 3932-3959; https://doi.org/10.3390/heritage7080186 - 30 Jul 2024
Cited by 9 | Viewed by 2001
Abstract
The present work investigates the physicochemical stability of spray paints when irradiated with artificial solar light (at spectral range 300–800 nm). This research highlights the importance of understanding the materials used in street art and public murals, recognising them as a significant component [...] Read more.
The present work investigates the physicochemical stability of spray paints when irradiated with artificial solar light (at spectral range 300–800 nm). This research highlights the importance of understanding the materials used in street art and public murals, recognising them as a significant component of contemporary cultural heritage. By examining the stability and degradation of spray paints toward solar light exposure, the study aims to contribute to the preservation of contemporary murals, which reflect current social and cultural narratives. A physicochemical approach was employed for the study of spray paints’ physical and thermal properties, as well as the effect of specific photochemical ageing reactions/processes. The photochemical ageing results were compared with reference (unaged) samples. Specifically, a multi-technique approach was applied using stereo microscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle measurement, colorimetry, glossimetry, differential scanning calorimetry (DSC), UV-Vis spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and pyrolysis-GC/MS (Py-GC/MS). The photodegradation of the spray paints occurred from the first 144 h of solar light irradiation, resulting in changes in morphology, colour, gloss, roughness, and wettability. Regarding photochemical stability, ageing seems to affect the binders more than the synthetic organic pigments and the inorganic fillers. In particular, acrylic binders showed small chemical changes, whereas the alkyd, nitrocellulose, and styrene binders underwent severe chemical modification. The results suggest that simulated daylight irradiation prompts the migration of additives toward the surface of the spray paint films. In addition, the results of the analyses on the white spray paints in comparison with the coloured paints (from the same manufacturer) showed that there seems to be an active distinct photoageing mechanism involving titanium dioxide, but the whole issue needs further investigation. Full article
(This article belongs to the Section Cultural Heritage)
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17 pages, 2108 KB  
Article
Plasma Rich in Growth Factors in Bone Regeneration: The Proximity to the Clot as a Differential Factor in Osteoblast Cell Behaviour
by Eduardo Anitua, Mar Zalduendo, Roberto Tierno and Mohammad Hamdan Alkhraisat
Dent. J. 2024, 12(5), 122; https://doi.org/10.3390/dj12050122 - 24 Apr 2024
Cited by 2 | Viewed by 3040
Abstract
The osteogenic differentiation process, by which bone marrow mesenchymal stem cells and osteoprogenitors transform into osteoblasts, is regulated by several growth factors, cytokines, and hormones. Plasma Rich in Growth Factors (PRGF) is a blood-derived preparation consisting of a plethora of bioactive molecules, also [...] Read more.
The osteogenic differentiation process, by which bone marrow mesenchymal stem cells and osteoprogenitors transform into osteoblasts, is regulated by several growth factors, cytokines, and hormones. Plasma Rich in Growth Factors (PRGF) is a blood-derived preparation consisting of a plethora of bioactive molecules, also susceptible to containing epigenetic factors such as ncRNAs and EVs, that stimulates tissue regeneration. The aim of this study was to investigate the effect of the PRGF clot formulation on osteogenic differentiation. Firstly, osteoblast cells were isolated and characterised. The proliferation of bone cells cultured onto PRGF clots or treated with PRGF supernatant was determined. Moreover, the gene expression of Runx2 (ID: 860), SP7 (ID: 121340), and ALPL (ID: 249) was analysed by one-step real-time quantitative polymerase chain reaction (RT-qPCR). Additionally, alkaline phosphatase (ALPL) activity determination was performed. The highest proliferative effect was achieved by the PRGF supernatant in all the study periods analysed. Concerning gene expression, the logRGE of Runx2 increased significantly in osteoblasts cultured with PRGF formulations compared with the control group, while that of SP7 increased significantly in osteoblasts grown on the PRGF clots. On the other hand, despite the fact that the PRGF supernatant induced ALPL up-regulation, significantly higher enzyme activity was detected for the PRGF clots in comparison with the supernatant formulation. According to our results, contact with the PRGF clot could promote a more advanced phase in the osteogenic process, associated to higher levels of ALPL activity. Furthermore, the PRGF clot releasate stimulated a higher proliferation rate in addition to reduced SP7 expression in the cells located at a distant ubication, leading to a less mature osteoblast stage. Thus, the spatial relationship between the PRGF clot and the osteoprogenitors cells could be a factor that influences regenerative outcomes. Full article
(This article belongs to the Special Issue Regenerative Approaches in Dental Sciences)
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9 pages, 635 KB  
Case Report
Suspected Hematuria: Adverse Effects of Rivaroxaban in Older Adult Treated for Atrial Fibrillation
by Aleksandra Rapaić, Ekaterina Milošević, Nemanja Todorović, Nataša Janjić, Mladena Lalić-Popović and Nataša Milošević
Reports 2024, 7(1), 11; https://doi.org/10.3390/reports7010011 - 8 Feb 2024
Viewed by 6471
Abstract
Background: The modern concept of pharmaceutical healthcare implies monitoring the pharmacotherapy outcomes and reporting adverse drug reactions. Objective: To present a suspected hematuria as the adverse rivaroxaban reaction in a patient with atrial fibrillation observed by pharmacists in a community pharmacy. Case presentation: [...] Read more.
Background: The modern concept of pharmaceutical healthcare implies monitoring the pharmacotherapy outcomes and reporting adverse drug reactions. Objective: To present a suspected hematuria as the adverse rivaroxaban reaction in a patient with atrial fibrillation observed by pharmacists in a community pharmacy. Case presentation: A 69-year-old female patient came to a pharmacy with a prescription for cranberry-based supplement. She was diagnosed with a mild urinary infection after experiencing blood in her urine for about two weeks. The pharmaceutical anamnesis revealed that the patient was treated with irbesartan and rivaroxaban. Rivaroxaban was applied for atrial fibrillation, and the patient was treated for nine months. The patient was treated with omeprazole gastro-resistant capsules for mild dyspepsia and stomach ache over a three-week period. The pharmacist counselled the patient to contact the clinician who introduced rivaroxaban, further suggesting substitution with different anticoagulant. Although the urine culture was negative, the physician introduced ciprofloxacin, which was followed by blood in the patient’s stool. Thus, gastroscopy, colonoscopy, and gynecological examination were advised. All findings were normal. Four days after rivaroxaban was substituted with acenocoumarol, no blood in the urine or stool was detected. Conclusions: Rivaroxaban can cause spot urine blood even when applied in therapeutic doses among older female patients when applied with omeprazole. Possible rivaroxaban interaction with omeprazole metabolites is suspected and should be carefully monitored. Full article
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12 pages, 6271 KB  
Article
Nickel Challenge In Vitro Affects CD38 and HLA-DR Expression in T Cell Subpopulations from the Blood of Patients with Nickel Allergy
by Metin Artuc, Torsten Zuberbier and Matthias Peiser
Int. J. Mol. Sci. 2024, 25(1), 298; https://doi.org/10.3390/ijms25010298 - 25 Dec 2023
Cited by 1 | Viewed by 2078
Abstract
Nickel allergy is a major health problem and shows clinical manifestation of contact eczema. The response of specific lymphocyte subpopulations in sensitized patients after new challenge to nickel has until now not been studied in detail. To evaluate if nickel-based elicitation reaction could [...] Read more.
Nickel allergy is a major health problem and shows clinical manifestation of contact eczema. The response of specific lymphocyte subpopulations in sensitized patients after new challenge to nickel has until now not been studied in detail. To evaluate if nickel-based elicitation reaction could be objectively identified by multi-parametric flow cytometry, immunophenotyping of specific T cells was applied. White blood cells from 7 patients (4 positive in patch test, 3 negative) were challenged by nickel and in vitro short-term culture. Standardized antibody-dye combinations, specific for T helper(h)1, Th17 and cytotoxic T cell activation, were selected according to the recommendations of Stanford Human Immune Monitoring Center. In cytotoxic CD8+CCR7+CD45RA+ T cells from patients suffering from nickel allergy, CD38 and HLA-DR were elevated comparing to healthy donors. After challenge to nickel in vitro both markers decreased in CD8+CCR7+CD45RA+ T cells but found up-regulated in CD4+CCR7+CD45RA+CCR6CXCR3+Th1 cells. Intracellular expression of T-bet and RORγt further indicated Th1 and Th17 cells. Finally, CD4+CD25+CCR4 T cells increased after challenge with nickel in PBMCs of patients with nickel allergy. Flow cytometry based quantification of T cell markers might be used as a specific and reliable method to detect chemical induced skin sensitization and confirm diagnostic patch testing in the clinics. Full article
(This article belongs to the Special Issue Skin Inflammation and Allergy)
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20 pages, 3329 KB  
Article
CREB Is Indispensable to KIT Function in Human Skin Mast Cells—A Positive Feedback Loop between CREB and KIT Orchestrates Skin Mast Cell Fate
by Gürkan Bal, Jean Schneikert, Zhuoran Li, Kristin Franke, Shiva Raj Tripathi, Torsten Zuberbier and Magda Babina
Cells 2024, 13(1), 42; https://doi.org/10.3390/cells13010042 - 24 Dec 2023
Cited by 6 | Viewed by 2829
Abstract
Skin mast cells (MCs) are critical effector cells in acute allergic reactions, and they contribute to chronic dermatoses like urticaria and atopic and contact dermatitis. KIT represents the cells‘ crucial receptor tyrosine kinase, which orchestrates proliferation, survival, and functional programs throughout the lifespan. [...] Read more.
Skin mast cells (MCs) are critical effector cells in acute allergic reactions, and they contribute to chronic dermatoses like urticaria and atopic and contact dermatitis. KIT represents the cells‘ crucial receptor tyrosine kinase, which orchestrates proliferation, survival, and functional programs throughout the lifespan. cAMP response element binding protein (CREB), an evolutionarily well-conserved transcription factor (TF), regulates multiple cellular programs, but its function in MCs is poorly understood. We recently reported that CREB is an effector of the SCF (Stem Cell Factor)/KIT axis. Here, we ask whether CREB may also act upstream of KIT to orchestrate its functioning. Primary human MCs were isolated from skin and cultured in SCF+IL-4 (Interleukin-4). Pharmacological inhibition (666-15) and RNA interference served to manipulate CREB function. We studied KIT expression using flow cytometry and RT-qPCR, KIT-mediated signaling using immunoblotting, and cell survival using scatterplot and caspase-3 activity. The proliferation and cycle phases were quantified following BrdU incorporation. Transient CREB perturbation resulted in reduced KIT expression. Conversely, microphthalmia transcription factor (MITF) was unnecessary for KIT maintenance. KIT attenuation secondary to CREB was associated with heavily impaired KIT functional outputs, like anti-apoptosis and cell cycle progression. Likewise, KIT-elicited phosphorylation of ERK1/2 (Extracellular Signal-Regulated Kinase 1/2), AKT, and STAT5 (Signal Transducer and Activator of Transcription) was substantially diminished upon CREB inhibition. Surprisingly, the longer-term interference of CREB led to complete cell elimination, in a way surpassing KIT inhibition. Collectively, we reveal CREB as non-redundant in MCs, with its absence being incompatible with skin MCs’ existence. Since SCF/KIT regulates CREB activity and, vice versa, CREB is required for KIT function, a positive feedforward loop between these elements dictates skin MCs’ fate. Full article
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13 pages, 5063 KB  
Article
Cytotoxicity, Differentiation, and Biocompatibility of Root-End Filling: A Comprehensive Study
by Ignacio Jimenez-Bueno, Rene Garcia-Contreras, Benjamin Aranda-Herrera, Hiroshi Sakagami, Christian Andrea Lopez-Ayuso, Hiroshi Nakajima, Carlos A. Jurado and Hamid Nurrohman
Biomimetics 2023, 8(7), 514; https://doi.org/10.3390/biomimetics8070514 - 29 Oct 2023
Cited by 2 | Viewed by 2770
Abstract
Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the cytotoxicity of the type of cell death through apoptosis and autophagy, and odontoblast cell-like differentiation effects of MTA, zinc [...] Read more.
Assessing the biocompatibility of endodontic root-end filling materials through cell line responses is both essential and of utmost importance. This study aimed to the cytotoxicity of the type of cell death through apoptosis and autophagy, and odontoblast cell-like differentiation effects of MTA, zinc oxide–eugenol, and two experimental Portland cements modified with bismuth (Portland Bi) and barium (Portland Ba) on primary cell cultures. Material and methods: The cells corresponded to human periodontal ligament and gingival fibroblasts (HPLF, HGF), human pulp cells (HPC), and human squamous carcinoma cells from three different patients (HSC-2, -3, -4). The cements were inoculcated in different concentrations for cytotoxicity evaluation, DNA fragmentation in electrophoresis, apoptosis caspase activation, and autophagy antigen reaction, odontoblast-like cells were differentiated and tested for mineral deposition. The data were subject to a non-parametric test. Results: All cements caused a dose-dependent reduction in cell viability. Contact with zinc oxide–eugenol induced neither DNA fragmentation nor apoptotic caspase-3 activation and autophagy inhibitors (3-methyladenine, bafilomycin). Portland Bi accelerated significantly (p < 0.05) the differentiation of odontoblast-like cells. Within the limitation of this study, it was concluded that Portland cement with bismuth exhibits cytocompatibility and promotes odontoblast-like cell differentiation. This research contributes valuable insights into biocompatibility, suggesting its potential use in endodontic repair and biomimetic remineralization. Full article
(This article belongs to the Special Issue Biomimetic Remineralization on Enamel and Dentin: 2nd Edition)
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18 pages, 3458 KB  
Article
Bioglass and Vitamin D3 Coatings for Titanium Implants: Osseointegration and Corrosion Protection
by Irina Negut, Gratiela Gradisteanu-Pircalabioru, Mihaela Dinu, Bogdan Bita, Anca Constantina Parau, Valentina Grumezescu, Carmen Ristoscu and Mariana Carmen Chifiriuc
Biomedicines 2023, 11(10), 2772; https://doi.org/10.3390/biomedicines11102772 - 12 Oct 2023
Cited by 9 | Viewed by 2515
Abstract
The use of MAPLE synthesized thin films based on BG and VD3 for improving the osseointegration and corrosion protection of Ti-like implant surfaces is reported. The distribution of chemical elements and functional groups was shown by FTIR spectrometry; the stoichiometry and chemical functional [...] Read more.
The use of MAPLE synthesized thin films based on BG and VD3 for improving the osseointegration and corrosion protection of Ti-like implant surfaces is reported. The distribution of chemical elements and functional groups was shown by FTIR spectrometry; the stoichiometry and chemical functional integrity of thin films after MAPLE deposition was preserved, optimal results being revealed especially for the BG+VD3_025 samples. The morphology and topography were examined by SEM and AFM, and revealed surfaces with many irregularities, favoring a good adhesion of cells. The thin films’ cytotoxicity and biocompatibility were evaluated in vitro at the morphological, biochemical, and molecular level. Following incubation with HDF cells, BG57+VD3_ 025 thin films showed the best degree of biocompatibility, as illustrated by the viability assay values. According to the LDH investigation, all tested samples had higher values compared to the unstimulated cells. The evaluation of cell morphology was performed by fluorescence microscopy following cultivation of HDF cells on the obtained thin films. The cultivation of HDF’s on the thin films did not induce major cellular changes. Cells cultured on the BG57+VD3_025 sample had similar morphology to that of unstimulated control cells. The inflammatory profile of human cells cultured on thin films obtained by MAPLE was analyzed by the ELISA technique. It was observed that the thin films did not change the pro- and anti-inflammatory profile of the HDF cells, the IL-6 and IL-10 levels being similar to those of the control sample. The wettability of the MAPLE thin films was investigated by the sessile drop method. A contact angle of 54.65° was measured for the sample coated with BG57+VD3_025. Electrochemical impedance spectroscopy gave a valuable insight into the electrochemical reactions occurring on the surface. Full article
(This article belongs to the Special Issue Materials for Biomedical Engineering and Regenerative Medicine)
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