The 2023 MDPI Annual Report has
been released!
 
16 pages, 4702 KiB  
Article
Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study
by Juan Guo, Lifang Zhang, Mi Wang, Yingchun Liu and Chenzhong Fei
Molecules 2024, 29(10), 2164; https://doi.org/10.3390/molecules29102164 (registering DOI) - 07 May 2024
Abstract
Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this [...] Read more.
Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL. Full article
(This article belongs to the Special Issue Veterinary Drugs—2nd Edition)
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3 pages, 165 KiB  
Editorial
Unlocking Potential and Limits of Kinase Inhibitors: The Highway to Enhanced Cancer Targeted Therapy
by Francesca Musumeci and Silvia Schenone
Pharmaceutics 2024, 16(5), 625; https://doi.org/10.3390/pharmaceutics16050625 (registering DOI) - 07 May 2024
Abstract
Kinases are a family of enzymes comprising over five hundred members, which, when overexpressed or hyperactivated, are implicated in the pathogenesis of numerous hematological and solid cancers [...] Full article
(This article belongs to the Special Issue Kinase Inhibitor for Cancer Therapy)
20 pages, 3412 KiB  
Article
Induction of FoxP3 Pre-mRNA Alternative Splicing to Enhance the Suppressive Activity of Regulatory T Cells from Amyotrophic Lateral Sclerosis Patients
by Dmitry D. Zhdanov, Yulia A. Gladilina, Varvara G. Blinova, Anna A. Abramova, Anastasia N. Shishparenok and Daria D. Eliseeva
Biomedicines 2024, 12(5), 1022; https://doi.org/10.3390/biomedicines12051022 (registering DOI) - 07 May 2024
Abstract
Forkhead box protein 3 (FoxP3) is a key transcription factor responsible for the development, maturation, and function of regulatory T cells (Tregs). The FoxP3 pre-mRNA is subject to alternative splicing, resulting in the translation of multiple splice variants. We have shown that Tregs [...] Read more.
Forkhead box protein 3 (FoxP3) is a key transcription factor responsible for the development, maturation, and function of regulatory T cells (Tregs). The FoxP3 pre-mRNA is subject to alternative splicing, resulting in the translation of multiple splice variants. We have shown that Tregs from patients with amyotrophic lateral sclerosis (ALS) have reduced expression of full-length (FL) FoxP3, while other truncated splice variants are expressed predominantly. A correlation was observed between the reduced number of Tregs in the peripheral blood of ALS patients, reduced total FoxP3 mRNA, and reduced mRNA of its FL splice variant. Induction of FL FoxP3 was achieved using splice-switching oligonucleotides capable of base pairing with FoxP3 pre-mRNA and selectively modulating the inclusion of exons 2 and 7 in the mature mRNA. Selective expression of FL FoxP3 resulted in the induction of CD127low, CD152, and Helios-positive cells, while the cell markers CD4 and CD25 were not altered. Such Tregs had an increased proliferative activity and a higher frequency of cell divisions per day. The increased suppressive activity of Tregs with the induced FL FoxP3 splice variant was associated with the increased synthesis of the pro-apoptotic granzymes A and B, and perforin, IL-10, and IL-35, which are responsible for contact-independent suppression, and with the increased ability to suppress telomerase in target cells. The upregulation of Treg suppressive and proliferative activity using splice-switching oligonucleotides to induce the predominant expression of the FoxP3 FL variant is a promising approach for regenerative cell therapy in Treg-associated diseases. Full article
(This article belongs to the Special Issue New Advances in the Role of Regulatory T Cells in Immunity)
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17 pages, 4261 KiB  
Article
A Humanized and Viable Animal Model for Congenital Adrenal Hyperplasia–CYP21A2-R484Q Mutant Mouse
by Shamini Ramkumar Thirumalasetty, Tina Schubert, Ronald Naumann, Ilka Reichardt, Marie-Luise Rohm, Dana Landgraf, Florian Gembardt, Mirko Peitzsch, Michaela F. Hartmann, Mihail Sarov, Stefan A. Wudy, Nicole Reisch, Angela Huebner and Katrin Koehler
Int. J. Mol. Sci. 2024, 25(10), 5062; https://doi.org/10.3390/ijms25105062 (registering DOI) - 07 May 2024
Abstract
Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in CYP21A2 [...] Read more.
Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in CYP21A2, causing 21-hydroxylase deficiency (21-OHD). Despite emerging treatment options for CAH, it is not always possible to physiologically replace cortisol levels and counteract hyperandrogenism. Moreover, there is a notable absence of an effective in vivo model for pre-clinical testing. In this work, we developed an animal model for CAH with the clinically relevant point mutation p.R484Q in the previously humanized CYP21A2 mouse strain. Mutant mice showed hyperplastic adrenals and exhibited reduced levels of corticosterone and 11-deoxycorticosterone and an increase in progesterone. Female mutants presented with higher aldosterone concentrations, but blood pressure remained similar between wildtype and mutant mice in both sexes. Male mutant mice have normal fertility with a typical testicular appearance, whereas female mutants are infertile, exhibit an abnormal ovarian structure, and remain in a consistent diestrus phase. Conclusively, we show that the animal model has the potential to contribute to testing new treatment options and to prevent comorbidities that result from hormone-related derangements and treatment-related side effects in CAH patients. Full article
(This article belongs to the Special Issue Molecular Aspects of Adrenal Diseases and Carcinoma)
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26 pages, 516 KiB  
Review
The Impact of Physical Exercise on Oxidative and Nitrosative Stress: Balancing the Benefits and Risks
by Qing Meng and Chun-Hsien Su
Antioxidants 2024, 13(5), 573; https://doi.org/10.3390/antiox13050573 (registering DOI) - 07 May 2024
Abstract
This review comprehensively evaluates the effects of physical exercise on oxidative and nitrosative stress, mainly focusing on the role of antioxidants. Using a narrative synthesis approach, data from empirical studies, reviews, systematic reviews, and meta-analyses published between 2004 and 2024 were collated from [...] Read more.
This review comprehensively evaluates the effects of physical exercise on oxidative and nitrosative stress, mainly focusing on the role of antioxidants. Using a narrative synthesis approach, data from empirical studies, reviews, systematic reviews, and meta-analyses published between 2004 and 2024 were collated from databases like PubMed, EBSCO (EDS), and Google Scholar, culminating in the inclusion of 41 studies. The quality of these studies was rigorously assessed to ensure the clarity of objectives, coherence in arguments, comprehensive literature coverage, and depth of critical analysis. Findings revealed that moderate exercise enhances antioxidant defenses through hormesis, while excessive exercise may exacerbate oxidative stress. The review also highlights that while natural dietary antioxidants are beneficial, high-dose supplements could impede the positive adaptations to exercise. In conclusion, the review calls for more focused research on tailored exercise and nutrition plans to further understand these complex interactions and optimize the health outcomes for athletes and the general population. Full article
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20 pages, 3041 KiB  
Article
Melatonin Mitigates Lead-Induced Oxidative Stress and Modifies Phospholipid Profile in Tobacco BY-2 Suspension Cells
by Agnieszka Kobylińska, Przemysław Bernat and Małgorzata Maria Posmyk
Int. J. Mol. Sci. 2024, 25(10), 5064; https://doi.org/10.3390/ijms25105064 (registering DOI) - 07 May 2024
Abstract
Many studies have shown that melatonin (an indoleamine) is an important molecule in plant physiology. It is known that this indoleamine is crucial during plant stress responses, especially by counteracting secondary oxidative stress (efficient direct and indirect antioxidant) and switching on different defense [...] Read more.
Many studies have shown that melatonin (an indoleamine) is an important molecule in plant physiology. It is known that this indoleamine is crucial during plant stress responses, especially by counteracting secondary oxidative stress (efficient direct and indirect antioxidant) and switching on different defense plant strategies. In this report, we present exogenous melatonin’s potential to protect lipid profile modification and membrane integrity in Nicotiana tabacum L. line Bright Yellow 2 (BY-2) cell culture exposed to lead. There are some reports of the positive effect of melatonin on animal cell membranes; ours is the first to report changes in the lipid profile in plant cells. The experiments were performed in the following variants: LS: cells cultured on unmodified LS medium—control; (ii) MEL: BY-2 cells cultured on LS medium with melatonin added from the beginning of culture; (iii) Pb: BY-2 cells cultured on LS medium with Pb2+ added on the 4th day of culture; (iv) MEL+Pb: BY-2 cells cultured on LS medium with melatonin added from the start of culture and stressed with Pb2+ added on the 4th day of culture. Lipidomic analysis of BY-2 cells revealed the presence of 40 different phospholipids. Exposing cells to lead led to the overproduction of ROS, altered fatty acid composition and increased PLD activity and subsequently elevated the level of phosphatidic acid at the cost of dropping the phosphatidylcholine. In the presence of lead, double-bond index elevation, mainly by higher quantities of linoleic (C18:2) and linolenic (C18:3) acids in the log phase of growth, was observed. In contrast, cells exposed to heavy metal but primed with melatonin showed more similarities with the control. Surprisingly, the overproduction of ROS caused of lipid peroxidation only in the stationary phase of growth, although considerable changes in lipid profiles were observed in the log phase of growth—just 4 h after lead administration. Our results indicate that the pretreatment of BY-2 with exogenous melatonin protected tobacco cells against membrane dysfunctions caused by oxidative stress (lipid oxidation), but also findings on a molecular level suggest the possible role of this indoleamine in the safeguarding of the membrane lipid composition that limited lead-provoked cell death. The presented research indicates a new mechanism of the defense strategy of plant cells generated by melatonin. Full article
(This article belongs to the Special Issue The Role of Melatonin in Plants 2.0)
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18 pages, 2155 KiB  
Article
Tillage and Straw Management Practices Influences Soil Nutrient Distribution: A Case Study from North-Eastern Romania
by Anca Elena Calistru, Feodor Filipov, Irina Gabriela Cara, Marius Cioboată, Denis Țopa and Gerard Jităreanu
Land 2024, 13(5), 625; https://doi.org/10.3390/land13050625 (registering DOI) - 07 May 2024
Abstract
Tillage practices govern crop quality and quantity through soil nutrient availability and crop root systems. A deeper knowledge of the impact of conservation tillage on soil chemical characteristics (such as pH, soil organic carbon, macro and micronutrient storage and distribution) is required for [...] Read more.
Tillage practices govern crop quality and quantity through soil nutrient availability and crop root systems. A deeper knowledge of the impact of conservation tillage on soil chemical characteristics (such as pH, soil organic carbon, macro and micronutrient storage and distribution) is required for both the promotion of agricultural sustainability and environmental preservation. This study assesses the changes in soil features and properties in the context of a long-field experiment with different tillage systems and straw management practices. Research findings revealed that compared with conventional tillage (CT) conservative tillage with partial straw retention (MT) and no-tillage with straw mulching (NT) substantially boosted the organic carbon (OC) (by 6–19%), total nitrogen (TN) (by 2–12%), and available potassium content (AK) (by 2–5%), in 0–30 cm soil depth. However, the stratification trend was observed for available macro and micronutrient content (Zn, Fe, Mn) in both conservative management practices. The concentration of Cu indicates a constant pattern through a 0–30 cm soil profile with a higher concentration under MT (1.41 mg kg−1) compared to NT (1.10 mg kg−1). In particular, the results failed to establish if conservation tillage can increase the total phosphorus (TP) and potassium content (TK), where only in surface 0–10 cm an increase was observed. This research also suggested that the X-ray fluorescence analysis (XRF) of total micronutrient content (Zn, Cu, Fe, Mn) is minimal or unpredictable with no substantial differences between the tillage systems and straw return management practices. These findings suggest that conservation tillage in north-eastern Romania might be optimal to maintain soil quality status and sustain high yields. Full article
(This article belongs to the Special Issue Soil Management for Soil Health)
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12 pages, 3207 KiB  
Article
Mathematical Evaluation of Population Changes of Lactobacillus acidophilus and Bifidobacterium animalis ssp. lactis as Free and Encapsulated Cells in Butter
by Rakesh Kaushik, Kritika Gaba, Sanjeev Anand and Gemechis Djira
Fermentation 2024, 10(5), 245; https://doi.org/10.3390/fermentation10050245 (registering DOI) - 07 May 2024
Abstract
Growing butter markets, domestically and globally, provide opportunities for value-added variants of butter. Adding probiotics to butter could boosts its bioactivity; however, maintaining probiotic viability during storage is a major challenge. Mathematical analysis of probiotic population changes could help improve our understanding of [...] Read more.
Growing butter markets, domestically and globally, provide opportunities for value-added variants of butter. Adding probiotics to butter could boosts its bioactivity; however, maintaining probiotic viability during storage is a major challenge. Mathematical analysis of probiotic population changes could help improve our understanding of how probiotics interact with butter and storage conditions. Two strains of probiotics in a 1:1 ratio as free cells or Whey Protein Hydrolysate–Maltodextrin (WPH-MD)-encapsulated cells, Lactobacillus acidophilus ATCC 4356 (LA5) and Bifidobacterium animalis ssp. lactis ATCC 27536 (BB12), were separately mixed into butter at 1% levels. Using analysis of covariance, a mathematical evaluation for probiotic population changes was performed by periodically determining viable counts, resulting in an adjusted R2 value of 0.98 and demonstrating a strong relationship between the dependent variable (log10 counts of probiotics) and independent variables (cell type, temperature of storage, and time of storage). After 21 days of storage, the number of free cells in butter dropped from 7.45 log10 CFU/g to 0.56 log10 CFU/g. On the other hand, it took 63 days for encapsulated cells to achieve 0.80 log10 CFU/g at the same temperature. The same trend persisted at −18 °C, indicating that the WPH-MD encapsulant had a protective effect. Full article
(This article belongs to the Special Issue High Quality Functional Food: Potential of Probiotics 2.0)
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19 pages, 6977 KiB  
Article
Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity
by Elia Ana Baltazar-García, Belinda Vargas-Guerrero, Ana Lima, Ricardo Boavida Ferreira, María Luisa Mendoza-Magaña, Mario Alberto Ramírez-Herrera, Tonatiuh Abimael Baltazar-Díaz, José Alfredo Domínguez-Rosales, Adriana María Salazar-Montes and Carmen Magdalena Gurrola-Díaz
Int. J. Mol. Sci. 2024, 25(10), 5063; https://doi.org/10.3390/ijms25105063 (registering DOI) - 07 May 2024
Abstract
Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, [...] Read more.
Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson’s trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity. Full article
(This article belongs to the Special Issue Natural Compounds in Health and Disease)
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13 pages, 248 KiB  
Article
Factors Associated with COVID-19 Vaccination Hesitancy and Most Frequently Vaccinated Status in a Japanese Population-Based Sample
by Aya Shirama, Andrew Stickley and Tomiki Sumiyoshi
Vaccines 2024, 12(5), 501; https://doi.org/10.3390/vaccines12050501 (registering DOI) - 07 May 2024
Abstract
While many countries across the world have had difficulty in providing continuous coronavirus disease (COVID-19) vaccine boosters, in Japan, the number of COVID-19 vaccinations has increased rapidly in the past two years to the point where the vaccination booster numbers are now at [...] Read more.
While many countries across the world have had difficulty in providing continuous coronavirus disease (COVID-19) vaccine boosters, in Japan, the number of COVID-19 vaccinations has increased rapidly in the past two years to the point where the vaccination booster numbers are now at the highest level in the world (by March 2023). Against this backdrop, this study aimed to determine the characteristics of individuals who either refused to be vaccinated or who were vaccinated multiple (five) times during this period. We analyzed data from a sample of 3710 Japanese adults that were collected in a nationwide, cross-sectional Internet survey that was undertaken in March 2023. Several demographics (e.g., age, education level, marital status, job status), medical conditions, daily smoking, and mental health/psychological factors (i.e., perceived stress, anxiety symptoms, loneliness) were associated with not having been vaccinated. Although the most frequently vaccinated status was also associated with some demographics (e.g., age, employment status), medical conditions, and daily smoking, other predictors such as having a COVID-19 infection history were unique to this outcome. Moreover, age-stratified analyses showed that depression (OR: 2.05, 95%CI: 1.08–3.89) and anxiety (OR: 3.87, 95%CI: 1.80–8.31) symptoms were associated with higher odds of being unvaccinated while loneliness was associated with lower odds for the most frequently vaccinated status (OR: 0.72, 95%CI: 0.54–0.96) among older adults (aged ≥ 60 years). The findings of this study indicate that many of the same factors are associated with vaccine hesitancy and being vaccinated multiple times among adults in Japan but that among older individuals, worse mental/psychological health problems may be important for vaccine hesitancy/infrequent vaccine uptake in an age range where the majority of individuals (57.7%) had been vaccinated five times. Full article
18 pages, 16288 KiB  
Article
Design and Study of a Sediment Erosion Test Device for a Single-Flow Channel in the Guide Apparatus of a Reaction Hydraulic Turbine
by Jiayang Pang, Xiao Chang, Yuanyuan Gang, Ziyao Zhou, Wenping Xiang, Lingjiu Zhou, Xiaobing Liu and Zhengwei Wang
J. Mar. Sci. Eng. 2024, 12(5), 777; https://doi.org/10.3390/jmse12050777 (registering DOI) - 07 May 2024
Abstract
Sediment erosion damage is one of the main causes of structural failure in reaction turbine units. To study the mechanism through which sediment erosion affects the water-guiding mechanism of a reaction turbine unit, this study obtained the average concentration and particle size of [...] Read more.
Sediment erosion damage is one of the main causes of structural failure in reaction turbine units. To study the mechanism through which sediment erosion affects the water-guiding mechanism of a reaction turbine unit, this study obtained the average concentration and particle size of sediment during the flood season based on the statistics of the measured sediment data from the power station. Additionally, the characteristics of the solid–liquid two-phase flow of the diversion components of the reaction hydraulic turbine were numerically calculated. Based on the velocity triangle change in the guide apparatus and the flow similarity principle, a flow-around wear test device for the guide apparatus of the reaction turbine was designed. Furthermore, the similarity of the sand–water flow field between the guide apparatus of the prototype unit and the test device was compared and analyzed. The results demonstrated that the sand–water flow field of the diversion components of the prototype unit was axisymmetric and exhibited a potential flow distribution. Additionally, uniform sand–water flow occurred within the guide apparatus, with a small sand–water velocity gradient near the wall of the stay vanes (SV) and the guide vanes (GV). The maximum volume fraction of sediment particles was observed in the tailing area of the spiral casing, indicating an enrichment phenomenon of sediment particles. The velocity of the sediment particles on the surface of the guide vane in the single-channel sediment wear test device and prototype unit ranged from 6.2 to 7.8 m/s, and the velocity of the sediment particles on the surface of the stay vane ranged from 5.1 to 14.6 m/s, and the difference of the sediment particles’ velocity near the wall was 1 to 3 m/s. The trailing vorticity of the guide vane reached a maximum of 120 s−1. Consequently, the single-channel sediment erosion test device can unveil the sediment erosion mechanism of the guide apparatus of a reaction turbine. Full article
(This article belongs to the Section Ocean Engineering)
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16 pages, 784 KiB  
Article
Outcome of Pulmonary Embolism with and without Ischemic Stroke
by Karsten Keller, Volker H. Schmitt, Omar Hahad and Lukas Hobohm
J. Clin. Med. 2024, 13(10), 2730; https://doi.org/10.3390/jcm13102730 (registering DOI) - 07 May 2024
Abstract
Background: Ischemic stroke is the second, and pulmonary embolism (PE) is the third most common cardiovascular cause of death after myocardial infarction. Data regarding risk factors for ischemic stroke in patients with acute PE are limited. Methods: Patients were selected by screening the [...] Read more.
Background: Ischemic stroke is the second, and pulmonary embolism (PE) is the third most common cardiovascular cause of death after myocardial infarction. Data regarding risk factors for ischemic stroke in patients with acute PE are limited. Methods: Patients were selected by screening the German nationwide in-patient sample for PE (ICD-code I26) and were stratified by ischemic stroke (ICD code I63) and compared. Results: The nationwide in-patient sample comprised 346,586 hospitalized PE patients (53.3% females) in Germany from 2011 to 2014; among these, 6704 (1.9%) patients had additionally an ischemic stroke. PE patients with ischemic stroke had a higher in-hospital mortality rate than those without (28.9% vs. 14.5%, p < 0.001). Ischemic stroke was independently associated with in-hospital death (OR 2.424, 95%CI 2.278–2.579, p < 0.001). Deep venous thrombosis and/or thrombophlebitis (DVT) combined with heart septal defect (OR 24.714 [95%CI 20.693–29.517], p < 0.001) as well as atrial fibrillation/flutter (OR 2.060 [95%CI 1.943–2.183], p < 0.001) were independent risk factors for stroke in PE patients. Systemic thrombolysis was associated with a better survival in PE patients with ischemic thrombolysis who underwent cardio-pulmonary resuscitation (CPR, OR 0.55 [95%CI 0.36–0.84], p = 0.006). Conclusions: Ischemic stroke did negatively affect the survival of PE. Combination of DVT and heart septal defect and atrial fibrillation/flutter were strong and independent risk factors for ischemic stroke in PE patients. In PE patients with ischemic stroke, who had to underwent CPR, systemic thrombolysis was associated with improved survival. Full article
(This article belongs to the Special Issue Targeted Therapies and Clinical Outcomes for Ischemic Stroke)
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14 pages, 561 KiB  
Review
Clinical and Paraclinical Considerations Regarding ki67’s Role in the Management of Differentiated Thyroid Carcinoma—A Literature Review
by Claudiu Peștean, Alexandru Pavel and Doina Piciu
Medicina 2024, 60(5), 769; https://doi.org/10.3390/medicina60050769 (registering DOI) - 07 May 2024
Abstract
Background and Objectives: The ki67 nuclear protein is a tool for diagnosis and prognosis in oncology that is used to evaluate cell proliferation. Differentiated thyroid carcinoma is usually a slow-growing neoplasm, the most common type being the papillary form. Some clinical and [...] Read more.
Background and Objectives: The ki67 nuclear protein is a tool for diagnosis and prognosis in oncology that is used to evaluate cell proliferation. Differentiated thyroid carcinoma is usually a slow-growing neoplasm, the most common type being the papillary form. Some clinical and pathological aspects may predict aggressive behaviour. There are reported cases of recurrence without clinico-pathological findings of aggressiveness. To obtain better predictions of the disease outcome in thyroid carcinoma, many immunohistochemical markers have been studied. The aim of this narrative literature review is to identify the benefits that ki67 may add to the management of patients with differentiated thyroid carcinoma, according to the latest evidence. Materials and Methods: We performed a search on the PubMed and Google Scholar databases using controlled vocabulary and keywords to find the most suitable published articles. A total number of sixty-eight items were identified, and five other articles were selected from other sources. After refining the selection, the inclusion criteria and exclusion criteria were applied, and a total number of twenty-nine articles were included in this literature review. Results and Discussion: The studies consist of retrospective studies (89.66%), case reports (6.9%) and literature reviews (3.45%), evaluating the role, implications and other parameters of ki67 as a diagnostic and/or prognostic tool. The statistical correlations between ki67 and other features were systematized as qualitative results of this review in order to improve the treatment strategies presented in the included articles. Conclusions: The included studies present converging data regarding most of the aspects concerning ki67. The ki67 proliferation index is a diagnostic/prognostic tool of interest in differentiated thyroid carcinoma and a good predictor of disease-free survival, disease recurrence and metastatic development. Prospective studies on large cohorts may add value for ki67 as a specific tool in the management strategy of differentiated thyroid carcinoma. Full article
(This article belongs to the Section Oncology)
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23 pages, 3761 KiB  
Article
Technical and Economic Aspects of Environmentally Sustainable Investment in Terms of the EU Taxonomy
by Józef Ciuła, Agnieszka Generowicz, Aneta Oleksy-Gębczyk, Anna Gronba-Chyła, Iwona Wiewiórska, Paweł Kwaśnicki, Piotr Herbut and Viktor Koval
Energies 2024, 17(10), 2239; https://doi.org/10.3390/en17102239 (registering DOI) - 07 May 2024
Abstract
Removing impurities that occur in landfill gas, from sulphur and silicon compounds, is crucial for the energetic use of biogas in a cogeneration unit for energy purposes. The aim of this study was to analyse the shaped activated carbon, examining its structure and [...] Read more.
Removing impurities that occur in landfill gas, from sulphur and silicon compounds, is crucial for the energetic use of biogas in a cogeneration unit for energy purposes. The aim of this study was to analyse the shaped activated carbon, examining its structure and elemental composition as part of the biogas purification. The qualitative study of the purified landfill gas performed in this study showed a significant overshoot of hydrogen sulphide at 304.1 ppm with respect to the gas engine manufacturer’s requirements, while the calculated hydrogen sulphide reduction efficiency was 24.58%. Examination of the surface of the spent carbon and its pores with a scanning microscope revealed a high level of clotting by sulphur compounds, which prevents proper reduction of this compound and reduces the efficiency of the treatment plant. Replacement of the activated carbon bed with a new one showed a hydrogen sulphide value of 7.5 ppm in the purified gas and a calculated reduction efficiency of 97.9%. The results of the study confirmed that continuous monitoring of the quality of the purified gas is necessary to control the adsorption properties of the activated carbon and can be used for the operation of gas engines in cogeneration units. The landfill gas treatment method described in this paper constitutes an environmentally sustainable project within the meaning of the EU regulation on the establishment of a framework to promote and facilitate this type of investment in terms of its financing and operation. The topic of the work fits into three key areas of broad research and implementation activities. The first, technological, is the transition to a low-carbon, sustainable and resource-efficient closed-loop economy; the second, environmental, pollution prevention and control. The third area is economics and finance in terms of making financial products available designed to reduce climate change and reporting on these activities. Full article
(This article belongs to the Special Issue New Challenges in Waste-to-Energy and Bioenergy Systems)
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40 pages, 15541 KiB  
Article
Post-Fracture Production Prediction with Production Segmentation and Well Logging: Harnessing Pipelines and Hyperparameter Tuning with GridSearchCV
by Yongtao Sun, Jinwei Wang, Tao Wang, Jingsong Li, Zhipeng Wei, Aibin Fan, Huisheng Liu, Shoucun Chen, Zhuo Zhang, Yuanyuan Chen and Lei Huang
Appl. Sci. 2024, 14(10), 3954; https://doi.org/10.3390/app14103954 (registering DOI) - 07 May 2024
Abstract
As the petroleum industry increasingly exploits unconventional reservoirs with low permeability and porosity, accurate predictions of post-fracture production are becoming critical for investment decisions, energy policy development, and environmental impact assessments. However, despite extensive research, accurately forecasting post-fracture production using well-log data continues [...] Read more.
As the petroleum industry increasingly exploits unconventional reservoirs with low permeability and porosity, accurate predictions of post-fracture production are becoming critical for investment decisions, energy policy development, and environmental impact assessments. However, despite extensive research, accurately forecasting post-fracture production using well-log data continues to be a complex challenge. This study introduces a new method of data volume expansion, which is to subdivide the gas production of each well on the first day according to the depth of logging data, and to rely on the correlation model between petrophysical parameters and gas production to accurately combine the gas production data while matching the accuracy of the well-log data. Twelve pipelines were constructed utilizing a range of techniques to fit the regression relationship between logging parameters and post-fracture gas production These included data preprocessing methods (StandardScaler and RobustScaler), feature extraction approaches (PCA and PolynomialFeatures), and advanced machine learning models (XGBoost, Random Forest, and neural networks). Hyperparameter optimization was executed via GridSearchCV. To assess the efficacy of diverse models, metrics including the coefficient of determination (R2), standard deviation (SD), Pearson correlation coefficient (PCC), mean absolute error (MAE), mean squared error (MSE), and root-mean-square error (RMSE) were invoked. Among the several pipelines explored, the PFS-NN exhibited excellent predictive capability in specific reservoir contexts. In essence, integrating machine learning with logging parameters can be used to effectively assess reservoir productivity at multi-meter formation scales. This strategy not only mitigates uncertainties endemic to reservoir exploration but also equips petroleum engineers with the ability to monitor reservoir dynamics, thereby facilitating reservoir development. Additionally, this approach provides reservoir engineers with an efficient means of reservoir performance oversight. Full article
(This article belongs to the Special Issue Advances in Geo-Energy Development and Enhanced Oil/Gas Recovery)
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19 pages, 1803 KiB  
Article
Eco-Sustainability of Soils in Baby-Leaf Crop Systems under Tunnel through the Application of C-Rich Inputs: Towards Combating Soil Degradation
by Enrica Picariello, Flavio Fornasier, Maurizio Bilotto, Emiliana Mignoli, Salvatore Baiano and Luigi Morra
Horticulturae 2024, 10(5), 476; https://doi.org/10.3390/horticulturae10050476 (registering DOI) - 07 May 2024
Abstract
Fresh-cut leafy vegetables are produced in Southern Italy in very intensive crop systems under tunnel greenhouses in which continuous cropping has triggered soil organic carbon (SOC) depletion and the risk of degradation of soil fertility. A two-year trial of soil organic amendment was [...] Read more.
Fresh-cut leafy vegetables are produced in Southern Italy in very intensive crop systems under tunnel greenhouses in which continuous cropping has triggered soil organic carbon (SOC) depletion and the risk of degradation of soil fertility. A two-year trial of soil organic amendment was carried out on a private farm producing baby-leaf crops on a very poor OC soil (<1%). Biowaste compost, two types of olive pomace composts and buffalo manure were compared to evaluate their ability to recover a positive SOC balance and sustain crop growth and yield. The effects on soil health and crop system were studied by measuring different aspects such as SOC stock change and SOC sequestration rate, soil microbial biomass and nine enzyme activities, yields of rocket and concentration of nitrates in leaves. Soil amendments were distributed once a year at doses of 15 and 30 Mg ha−1 as fresh matter without integration of mineral fertilizers. In our study, the SOC stock improved in the amended soils in a range of 4–6 Mg ha−1, except for dose 30 of buffalo manure, with the highest values where biowaste compost was applied. Our data showed an increase in biological parameters in all the amended soils with respect to Control. In soil amended with olive pomace, however, compost mineralization rates likely did not match crops’ nutrient needs so the yields of rocket were lower than with the biowaste compost and buffalo manure. Biowaste compost showed the best results as it balanced the best C conversion efficiency, the higher increment of SOC and yields of rocket. Full article
(This article belongs to the Section Plant Nutrition)
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28 pages, 6039 KiB  
Review
Innovations in Electric Current-Assisted Sintering for SOFC: A Review of Advances in Flash Sintering and Ultrafast High-Temperature Sintering
by Jiajia Wu, Xiaohu Wu, Yan Gao and Zilin Yan
Appl. Sci. 2024, 14(10), 3953; https://doi.org/10.3390/app14103953 (registering DOI) - 07 May 2024
Abstract
This review discusses the groundbreaking advancements in electric current-assisted sintering techniques, specifically Flash Sintering (FS) and Ultrafast High-Temperature Sintering (UHS), for their application in Solid Oxide Fuel Cells (SOFCs). These innovative sintering methods have demonstrated remarkable potential in enhancing the efficiency and quality [...] Read more.
This review discusses the groundbreaking advancements in electric current-assisted sintering techniques, specifically Flash Sintering (FS) and Ultrafast High-Temperature Sintering (UHS), for their application in Solid Oxide Fuel Cells (SOFCs). These innovative sintering methods have demonstrated remarkable potential in enhancing the efficiency and quality of SOFC manufacturing by significantly lowering sintering temperatures and durations, thereby mitigating energy consumption and cost. By providing a detailed overview of the mechanisms, process parameters, and material characteristics associated with FS and UHS, this paper sheds light on their pivotal role in the fabrication of SOFC components such as electrolytes, electrodes, multilayered materials, and interconnect coatings. The advantages, challenges, and prospective opportunities of these sintering technologies in propelling SOFC advancements are thoroughly assessed, underlining their transformative impact on the future of clean and efficient energy production technologies. Full article
(This article belongs to the Special Issue Materials Development and Potential Applications of Ceramics)
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15 pages, 3239 KiB  
Article
Ketogenic Diet Induced Shifts in the Gut Microbiome Associate with Changes to Inflammatory Cytokines and Brain-Related miRNAs in Children with Autism Spectrum Disorder
by Nina P. Allan, Brennan Y. Yamamoto, Braden P. Kunihiro, Chandler K. L. Nunokawa, Noelle C. Rubas, Riley K. Wells, Lesley Umeda, Krit Phankitnirundorn, Amada Torres, Rafael Peres, Emi Takahashi and Alika K. Maunakea
Nutrients 2024, 16(10), 1401; https://doi.org/10.3390/nu16101401 (registering DOI) - 07 May 2024
Abstract
In this interventional pilot study, we investigated the effects of a modified ketogenic diet (KD) on children with autism spectrum disorder (ASD). We previously observed improved behavioral symptoms in this cohort following the KD; this trial was registered with Clinicaltrials.gov (NCT02477904). This report [...] Read more.
In this interventional pilot study, we investigated the effects of a modified ketogenic diet (KD) on children with autism spectrum disorder (ASD). We previously observed improved behavioral symptoms in this cohort following the KD; this trial was registered with Clinicaltrials.gov (NCT02477904). This report details the alterations observed in the microbiota, inflammation markers, and microRNAs of seven children following a KD for a duration of 4 months. Our analysis included blood and stool samples, collected before and after the KD. After 4 months follow up, we found that the KD led to decreased plasma levels of proinflammatory cytokines (IL-12p70 and IL-1b) and brain-derived neurotrophic factor (BDNF). Additionally, we observed changes in the gut microbiome, increased expression of butyrate kinase in the gut, and altered levels of BDNF-associated miRNAs in the plasma. These cohort findings suggest that the KD may positively influence ASD sociability, as previously observed, by reducing inflammation, reversing gut microbial dysbiosis, and impacting the BDNF pathway related to brain activity. Full article
(This article belongs to the Special Issue Clinical Impact of Ketogenic Diet)
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19 pages, 507 KiB  
Article
Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis
by Anca Moțățăianu, Ion Bogdan Mănescu, Georgiana Șerban, Laura Bărcuțean, Valentin Ion, Rodica Bălașa and Sebastian Andone
Int. J. Mol. Sci. 2024, 25(10), 5059; https://doi.org/10.3390/ijms25105059 (registering DOI) - 07 May 2024
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS patients. A cross-sectional study was conducted involving 44 ALS patients recruited from a tertiary care center. Serum levels of insulin, total amylin, C-peptide, active ghrelin, GIP (gastric inhibitory peptide), GLP-1 active (glucagon-like peptide-1), glucagon, PYY (peptide YY), PP (pancreatic polypeptide), leptin, interleukin-6, MCP-1 (monocyte chemoattractant protein-1), and TNFα (tumor necrosis factor alpha) were measured, and correlations with ALSFRS-R, evolution scores, and biomarkers were analyzed using Spearman correlation coefficients. Subgroup analyses based on ALS subtypes, progression pattern of disease, and disease progression rate patterns were performed. Significant correlations were observed between metabolic hormones and ALS evolution scores. Insulin and amylin exhibited strong correlations with disease progression and clinical functional outcomes, with insulin showing particularly robust associations. Other hormones such as C-peptide, leptin, and GLP-1 also showed correlations with ALS progression and functional status. Subgroup analyses revealed differences in hormone levels based on sex and disease evolution patterns, with male patients showing higher amylin and glucagon levels. ALS patients with slower disease progression exhibited elevated levels of amylin and insulin. Our findings suggest a potential role for metabolic hormones in modulating ALS progression and functional outcomes. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic implications of targeting metabolic pathways in ALS management. Full article
(This article belongs to the Special Issue Molecular Research of Amyotrophic Lateral Sclerosis)
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11 pages, 1351 KiB  
Article
Individualized Supplementation of Immunoactive Micronutrients and Severity of Upper Respiratory Infection Symptoms—A Randomized Intervention Study
by Melanie Haas, Beate Brandl, Laura Schinhammer and Thomas Skurk
Nutrients 2024, 16(10), 1400; https://doi.org/10.3390/nu16101400 (registering DOI) - 07 May 2024
Abstract
Certain micronutrients exhibit immunomodulatory effects. However, no intervention has yet investigated the effect of individualized supplementation on the severity of upper respiratory tract infections (URIs). Therefore, we investigated whether a personalized supplementation moderates the incidence and severity of URI. Selenium, zinc, and vitamin [...] Read more.
Certain micronutrients exhibit immunomodulatory effects. However, no intervention has yet investigated the effect of individualized supplementation on the severity of upper respiratory tract infections (URIs). Therefore, we investigated whether a personalized supplementation moderates the incidence and severity of URI. Selenium, zinc, and vitamin D were measured in dried blood spots from 59 healthy participants. Accordingly, a personalized supplement was provided with or without the respective micronutrients. We used WURSS-21 questionnaires to assess the disease status. The blood values converged during the intervention and micronutrients no longer differed between treated and untreated volunteers at the end of the intervention period. The incidence and severity of the illness did not significantly differ between the groups. However, when analyzing the WURSS-21 scores by the intention to treat, the initially randomized treatment arm revealed a significantly higher score than the placebo arm. Upon acute administration, individualized combinations of selenium, zinc and vitamin D do not reduce the number, or contribute to a milder course of URIs. Therefore, supplementation in acute infectious situations seems questionable. Further studies must address the habitual diet in more detail, to better understand the impact of individual micronutrient status on the prevention of URI. Full article
(This article belongs to the Section Micronutrients and Human Health)
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12 pages, 1649 KiB  
Article
Phenotypic and Genomic Characterization of Pseudomonas wuhanensis sp. nov., a Novel Species with Promising Features as a Potential Plant Growth-Promoting and Biocontrol Agent
by Jiawei Hou, Kaiji Liao, Yong-Jie Zhang, Jun-Zhou Li and Hai-Lei Wei
Microorganisms 2024, 12(5), 944; https://doi.org/10.3390/microorganisms12050944 (registering DOI) - 07 May 2024
Abstract
Plant growth-promoting rhizobacterial strain FP607T was isolated from the rhizosphere of beets in Wuhan, China. Strain FP607T exhibited significant antagonism toward several phytopathogenic bacteria, indicating that FP607T may produce antimicrobial metabolites and has a stronger biocontrol efficacy against plant pathogens. [...] Read more.
Plant growth-promoting rhizobacterial strain FP607T was isolated from the rhizosphere of beets in Wuhan, China. Strain FP607T exhibited significant antagonism toward several phytopathogenic bacteria, indicating that FP607T may produce antimicrobial metabolites and has a stronger biocontrol efficacy against plant pathogens. Growth-promoting tests showed that FP607T produced indole-3-acetic acid (IAA), NH3, and ferritin. The genome sequence of strain FP607T was 6,590,972 bp long with 59.0% G + C content. The optimum temperature range was 25–30 °C, and the optimum pH was 7. The cells of strain FP607T were Gram-negative, short, and rod-shaped, with polar flagella. The colonies on the King’s B (KB) agar plates were light yellow, smooth, and circular, with regular edges. A phylogenetic analysis of the 16S rRNA sequence and a multilocus sequence analysis (MLSA) showed that strain FP607T was most closely related to the type of strain Pseudomonas farris SWRI79T. Based on a polyphasic taxonomic approach, strain FP607T was identified as a novel species within the genus Pseudomonas, for which the name Pseudomonas wuhanensis sp. nov. was proposed. The type of strain used was FP607T (JCM 35688, CGMCC 27743, and ACCC 62446). Full article
(This article belongs to the Section Microbiomes)
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10 pages, 571 KiB  
Article
Tracheostomy Timing in Unselected Critically Ill Patients with Prolonged Intubation: A Prospective Cohort Study
by Pınar Tekin and Azime Bulut
J. Clin. Med. 2024, 13(10), 2729; https://doi.org/10.3390/jcm13102729 (registering DOI) - 07 May 2024
Abstract
Background: Tracheostomy procedures are performed in the intensive care unit (ICU) for prolonged intubation, unsuccessful weaning and infection prevention through either percutaneous or surgical techniques. This study aimed to outline the impact of tracheostomy timing in the ICU on mortality, need for [...] Read more.
Background: Tracheostomy procedures are performed in the intensive care unit (ICU) for prolonged intubation, unsuccessful weaning and infection prevention through either percutaneous or surgical techniques. This study aimed to outline the impact of tracheostomy timing in the ICU on mortality, need for mechanical ventilation, and complications. Methods: Patients were included in the study on the day of tracheostomy. Demographic information, tracheostomy timing, technique, complications, sedation requirement and need for mechanical ventilation at discharge were recorded by an anesthesiologist, including the pre-tracheostomy period. Results: Tracheostomy was performed on 33 patients during the first 14 days of intubation and on 54 patients on the 15th day and beyond. There was no significant difference between the tracheostomy timing and mortality, sedation requirement, or weaning from the ventilator. We observed that patients who underwent tracheostomy with the surgical technique experienced more complications, but there was no significant difference. Tracheostomy performed after the 14th day was shown to be associated with prolonged hospital stay. Conclusions: Early tracheostomy does not have any influence on the need for mechanical ventilation, sedation and mortality. The optimal timing for tracheostomy is still controversial. We are of the opinion that randomized controlled trials involving patient groups with similar survival expectations are needed. Full article
(This article belongs to the Section Intensive Care)
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14 pages, 2032 KiB  
Article
Imaging Approach in the Diagnostics and Evaluation of the Psoriasis Plaque: A Preliminary Study and Literature Review
by Mircea Negrutiu, Sorina Danescu, Theodor Popa, Monica Focsan, Stefan Cristian Vesa, Florin Szasz and Adrian Baican
Diagnostics 2024, 14(10), 969; https://doi.org/10.3390/diagnostics14100969 (registering DOI) - 07 May 2024
Abstract
(1) Background: the aim of the study was to demonstrate its usefulness in the field of imaging evaluation of plaque morphology in psoriasis vulgaris, with an emphasis on the use of confocal microscopy and other advanced skin-imaging techniques. (2) Methods: we conducted a [...] Read more.
(1) Background: the aim of the study was to demonstrate its usefulness in the field of imaging evaluation of plaque morphology in psoriasis vulgaris, with an emphasis on the use of confocal microscopy and other advanced skin-imaging techniques. (2) Methods: we conducted a prospective study over two years (July 2022–April 2024), on patients diagnosed with moderate or severe psoriasis vulgaris, treated in the dermatology department of our institution. We selected 30 patients, of whom 15 became eligible according to the inclusion and the exclusion criteria. A total of 60 psoriasis plaques were analyzed by dermatoscopy using a Delta 30 dermatoscope and Vidix 4.0 videodermoscope (VD), by cutaneous ultrasound (US) using a high-resolution 20 MHz linear probe, and by confocal microscopy, along with histopathological analysis. (3) Results: the study included fifteen patients with vulgar psoriasis, diagnosed histopathologically, of whom six were women and nine were men, with an average age of 55. Between two and six plaques per patient were selected and a total of sixty psoriasis plaques were analyzed by non-invasive imaging techniques. Twelve lesions were analyzed with ex vivo fluorescence confocal microscopy (FCM), compared to histology. US showed that the hyperechoic band and the lack of damage to the subcutaneous tissue were the most common criteria. The epidermis and dermis were found to be thicker in the area of psoriasis plaques compared to healthy skin. Dermatoscopy showed that the specific aspect of psoriasis plaques localized on the limbs and trunk was a lesion with an erythematous background, with dotted vessels with regular distribution on the surface and covered by white scales with diffuse distribution. The presence of bushy vessels with medium condensation was the most frequently identified pattern on VD. Good correlations were identified between the histological criteria and those obtained through confocal microscopy. (4) Conclusions: the assessment and monitoring of patients with psoriasis vulgaris can be conducted in a more complete and all-encompassing manner by incorporating dermatoscopy, ultrasonography, and confocal microscopy in clinical practice. Full article
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