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Search Results (21,302)

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15 pages, 1904 KiB  
Article
The Dynamics of Transaminase and Alkaline Phosphatase Activities in the “Mother–Placenta–Fetus” Functional System
by Elena Kolodkina and Sergey Lytaev
Biomedicines 2025, 13(3), 626; https://doi.org/10.3390/biomedicines13030626 - 4 Mar 2025
Abstract
Background: The timing of delivery depends on the condition of the fetus and the mother’s body, which is reflected in both the incretion of enzymes in the pregnant woman’s body and their use by the developing fetus in the anabolic process. The aim: [...] Read more.
Background: The timing of delivery depends on the condition of the fetus and the mother’s body, which is reflected in both the incretion of enzymes in the pregnant woman’s body and their use by the developing fetus in the anabolic process. The aim: This work was aimed to analyze the activities of transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and alkaline phosphatase (AlPh) in liquid media (blood serum, amniotic fluid, umbilical cord blood, and placental homogenate) in pregnant women in each trimester of pregnancy and in the postpartum period, considering the timing and type of delivery (term, premature or late delivery, or cesarean section). Methods: Data from studies in non-pregnant (n = 45) and pregnant (n = 193) women, including women in labor with different delivery timings (term, premature, and late) and types of delivery (natural birth or cesarean section), were analyzed. Amniotic fluid, umbilical cord blood, and the placental homogenate were collected during labor. The de Ritis coefficient (AST/ALT) was calculated. Alkaline phosphatase activity was determined using the standard constant-time method using Lahema diagnosticum biotests, and transaminase activity was determined using the colorimetric dinitrophenylhydrazine method, according to Reitman and Frenkel. Outcomes: The highest alkaline phosphatase activity was recorded in the placenta homogenate (6906.2 ± 208.1 U/mL) in pregnant women who gave birth at term. The highest transaminase activity was found in umbilical cord blood and, in particular, in the placenta in pregnant women with premature and late births. Conclusions: The significant role of transaminases and alkaline phosphatase in the transport functions of the histohematic barriers of the mother and fetus was established, which provides a mechanism for the constancy of enzyme levels in blood plasma. Full article
(This article belongs to the Special Issue Advances in Fetal Medicine and Neonatology)
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<p>The relationship between the pathways and organs of secretion and incretion of ALT, AST, and AlPh (original).</p>
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<p>Flow chart (design) of this study. Studies of blood sera in pregnant women in each trimester and after birth were performed. All remaining studies were singular.</p>
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<p>Comparative dynamics of the activities of transaminases (AST and ALT) and alkaline phosphatase in blood sera of non-pregnant and pregnant women with timely deliveries. Note: Left axis—transaminases (U/mL); right axis—alkaline phosphatase (U/mL).</p>
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<p>Transaminase activity of blood sera (U/mL) in the control group and pregnant women who gave birth on time, during trimesters of pregnancy, and after childbirth.</p>
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<p>Comparative dynamics of transaminase activity (AST and ALT) and alkaline phosphatase in blood sera of non-pregnant and pregnant women with premature births. Note: 6347—AlPh level; see <a href="#biomedicines-13-00626-f003" class="html-fig">Figure 3</a>.</p>
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<p>Transaminase activity in blood sera (U/mL) of the control group and pregnant women with premature deliveries in the trimesters of pregnancy and after childbirth.</p>
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<p>Comparative dynamics of transaminase activity (AST and ALT) and alkaline phosphatase in blood sera of non-pregnant and pregnant women with late deliveries. Note: 6740—AlPh level; see <a href="#biomedicines-13-00626-f001" class="html-fig">Figure 1</a>.</p>
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<p>Comparative dynamics of transaminase activity (AST and ALT) and alkaline phosphatase in blood sera of non-pregnant and pregnant women with cesarean sections. Note: 7522—AlPh level; see <a href="#biomedicines-13-00626-f001" class="html-fig">Figure 1</a>.</p>
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11 pages, 672 KiB  
Review
The Role of Temperature on Inflammation and Coagulation: Should We Apply Temperature Treatments for Hemophilic Arthropathy?
by Alice Maria Brancato, Laura Caliogna, Alessandra Monzio Compagnoni, Elena Cornella, Camilla Torriani, Micaela Berni, Liliana De Felice, Eugenio Jannelli, Mario Mosconi and Gianluigi Pasta
Int. J. Mol. Sci. 2025, 26(5), 2282; https://doi.org/10.3390/ijms26052282 - 4 Mar 2025
Viewed by 14
Abstract
Hemophilic arthropathy (HA) is a complication of hemophilia, which is a genetic disorder characterized by a deficiency in blood clotting factors. HA is characterized by joint damage with inflammatory responses, pain, and movement limitations due to recurrent bleeding in the joints. The inflammatory [...] Read more.
Hemophilic arthropathy (HA) is a complication of hemophilia, which is a genetic disorder characterized by a deficiency in blood clotting factors. HA is characterized by joint damage with inflammatory responses, pain, and movement limitations due to recurrent bleeding in the joints. The inflammatory reactions contribute to the activation of coagulation factors, which can exacerbate bleeding and further damage the affected joints. Therefore, the interaction between inflammation and coagulation plays a crucial role in the progression and complications of HA. Management strategies often focus both on inflammation and coagulation to alleviate symptoms and preserve joint function. Temperature can influence the inflammatory response and coagulation. The aim of this work was to understand how temperature management can positively or negatively influence the HA. We have carried out a narrative review of the available literature. This review explores the impacts of temperature on biological processes, and it discusses the possible clinical implications for the HA treatment. Our research shows that cold exposure has anti-inflammatory and analgesic effects, while heat is linked to pro-inflammatory cytokine release. Both hot and cold treatments are ill-advised for hemophilia patients. Heat stimulates neo-angiogenesis, and cold hampers coagulation, posing risks for increased bleeding in individuals with hemophilia. Full article
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<p>Prisma 2020 flow diagram for new systematic reviews which included searches of databases, registers, and other sources.</p>
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<p>Summary of the main effects of cold exposure and heat exposure.</p>
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45 pages, 997 KiB  
Systematic Review
Insurance Payor Status and Outcomes in Pediatric Sports-Related Injuries: A Rapid Review
by Katherine M. Kutzer, Lulla V. Kiwinda, Daniel Yang, John Kyle Mitchell, Emily J. Luo, Emily J. Harman, Stephanie Hendren, Kendall E. Bradley and Brian C. Lau
Clin. Pract. 2025, 15(3), 52; https://doi.org/10.3390/clinpract15030052 - 4 Mar 2025
Viewed by 66
Abstract
Introduction: The rise in youth sports participation has led to an increase in pediatric sports-related injuries in the United States, contributing to growing healthcare costs and exacerbating socioeconomic disparities. Insurance payor status is a critical factor influencing access to care, treatment delays, [...] Read more.
Introduction: The rise in youth sports participation has led to an increase in pediatric sports-related injuries in the United States, contributing to growing healthcare costs and exacerbating socioeconomic disparities. Insurance payor status is a critical factor influencing access to care, treatment delays, and health outcomes. This study examines the association between insurance payor status and outcomes in pediatric sports-related injuries. Methods: A systematic review of the Medline database was conducted. Included studies reported insurance payor status and pediatric sports orthopedic patient outcomes following surgery. Outcomes included time to be seen by a provider, treatment access, complication and revision rates, postoperative Emergency Department (ED)/Urgent Care utilization, readmission rates, hospital length of stay, pain, functional scores, discharge destinations, return to activity, and follow-up. Results: A total of 35 studies comprising 535,891 pediatric patients were included. Publicly insured or uninsured patients consistently experienced significant delays in accessing care, with average wait times for clinic visits, imaging, and surgery up to six times longer compared to privately insured patients. These delays were associated with worsened injury severity, higher rates of postoperative complications, and poorer functional outcomes. Publicly insured patients were less likely to receive advanced treatments such as bracing or physical therapy, further compounding disparities. Minority groups faced delays even when controlling for insurance status. Conclusions: Public and uninsured pediatric patients face systemic barriers to timely and equitable care, resulting in worse outcomes following sports-related injuries. Future research should explore targeted solutions to ensure equitable care for this vulnerable population. Full article
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<p>PRISMA flow diagram.</p>
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<p>Summary of key findings. (<b>a</b>) Publicly insured patients experienced delays compared to privately insured patients, including longer times to clinic [<a href="#B15-clinpract-15-00052" class="html-bibr">15</a>], imaging [<a href="#B35-clinpract-15-00052" class="html-bibr">35</a>], and surgery [<a href="#B18-clinpract-15-00052" class="html-bibr">18</a>]. (<b>b</b>) Treatment course shows publicly insured patients had more injury-related ED visits [<a href="#B42-clinpract-15-00052" class="html-bibr">42</a>], higher rates of casting compared to bracing, longer hospital stays [<a href="#B37-clinpract-15-00052" class="html-bibr">37</a>], and fewer postoperative physical therapy appointments [<a href="#B18-clinpract-15-00052" class="html-bibr">18</a>]. (<b>c</b>) Postoperative complications revealed higher rates of repeat dislocation in publicly insured patients [<a href="#B27-clinpract-15-00052" class="html-bibr">27</a>], while graft rupture was more common among privately insured patients [<a href="#B18-clinpract-15-00052" class="html-bibr">18</a>]. Reoperation rates were higher in publicly insured patients [<a href="#B27-clinpract-15-00052" class="html-bibr">27</a>]. (<b>d</b>) Patient-reported outcomes show that publicly insured patients experienced lower rates of functional recovery, including reduced range of motion [<a href="#B36-clinpract-15-00052" class="html-bibr">36</a>], lower hop test pass rates [<a href="#B23-clinpract-15-00052" class="html-bibr">23</a>], and lower return-to-sport clearance rates [<a href="#B18-clinpract-15-00052" class="html-bibr">18</a>]. Privately insured patients were more likely to receive postoperative opioids [<a href="#B16-clinpract-15-00052" class="html-bibr">16</a>].</p>
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<p>Surgical wait times and incidence of medial meniscus tears in private vs. government-insured patients. (Zoller 2017 [<a href="#B49-clinpract-15-00052" class="html-bibr">49</a>])—This study shows a significant increase in medial meniscal tear incidence, decrease in preoperative scores, and worse tear severity with surgical wait time &gt;6 months. Public insurance was a risk factor for longer surgical wait time and meniscus tear. There was a significant association between government insurance and surgical wait time &gt;3 months (<span class="html-italic">p</span> &lt; 0.001, OR 12.4), surgical wait time &gt;6 months (<span class="html-italic">p</span> &lt; 0.001, OR 7.8), and significant tears. ** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Delays to care among college-aged patients. (Johnson 2019 [<a href="#B28-clinpract-15-00052" class="html-bibr">28</a>])—Publicly insured and uninsured pediatric and college-aged patients faced significant barriers in accessing orthopedic services, as demonstrated by substantially longer times between the initial injury and referral to an orthopedic evaluation and surgery; however, these socioeconomic factors did not affect the rate of surgical management. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001, *** <span class="html-italic">p</span> &lt; 0.0001.</p>
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22 pages, 16830 KiB  
Review
Personalized Diagnoses for Those Born with Congenitally Malformed Hearts
by Adrian C. Crucean, Diane E. Spicer, Justin T. Tretter, Rohit Loomba and Robert H. Anderson
J. Pers. Med. 2025, 15(3), 102; https://doi.org/10.3390/jpm15030102 - 4 Mar 2025
Viewed by 102
Abstract
Background/Objectives: It is increasingly realized that the advances in diagnosis and treatment for those born with congenitally malformed hearts have now resulted in avoidance of morbidity being equally as important as avoiding postoperative mortality. Detailed personalized diagnoses will now be key to [...] Read more.
Background/Objectives: It is increasingly realized that the advances in diagnosis and treatment for those born with congenitally malformed hearts have now resulted in avoidance of morbidity being equally as important as avoiding postoperative mortality. Detailed personalized diagnoses will now be key to achieve such improvements. Methods: We have reviewed our own experience in diagnosing major phenotypic variations on selected congenital cardiac malformations, showing that the ability to personalize the findings is at hand, although not always to date universally employed. Results: We have chosen four categories to illustrate how the definitions now provided by the International Nomenclature Society, and incorporated in the 11th iteration of the International Classification of Disease, make it possible to provide personalized diagnoses. The lesions chosen for review are the arrangement of the atrial appendages, the lesions permitting interatrial shunting, the options in the setting of deficient ventricular septation, and the abnormal morphology of the aortic root. We show that not all centers, as yet, are taking advances of these opportunities at hand to tailor the chosen treatments. Conclusions: Detailed phenotypic definitions have now been provided for all the major congenital cardiac malformations. Use of these definitions should now provide personalized medicine for all those born with malformed hearts. As yet, the definitions are not used to their full effect. Full article
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<p>(<b>A</b>,<b>B</b>) have been prepared by cutting back the atrial myocardium so as to permit assessment of the atrioventricular junctions from above, with the left side seen to the right hand of the observer. (<b>C</b>) is a virtual dissection of a computed tomographic dataset producing a comparable view of the atrioventricular junctions. (<b>A</b>) shows the usual arrangement, with (<b>B</b>,<b>C</b>) showing the arrangements as seen when the atrial appendages are isomeric, with (<b>B</b>) showing right isomerism, and (<b>C</b>) left isomerism.</p>
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<p>The right atrium in this heart has been opened to show the presence of the two channels permitting interatrial shunting that are true “septal defects”. There is a large defect in the floor of the oval fossa, present because the flap valve derived from the primary atrial septum, is insufficiently large to overlap the rims of the fossa. In addition, there is a second vestibular defect in the antero-inferior buttress, which is the true second atrial septum (see text for further discussion).</p>
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<p>The images show the features of the channels that permit interatrial shunting whilst not being due to deficient atrial septation. (<b>A</b>) shows a superior sinus venosus defect, as seen through the opened right atrium. (<b>B</b>) shows a coronary sinus defect, shown through the opened left atrium. Note the presence of the connection of a persistent left superior caval vein to the atrial roof. (<b>C</b>) shows the so-called “ostium primum” defect, which is an atrioventricular septal defect (AVSD) but with shunting confined at atrial level due to the attachment of the bridging leaflets of the common atrioventricular valve to the crest of the scooped-out ventricular septum. The white star with red borders shows the site of the anticipated atrioventricular node at the apex of the triangle of Koch. This node, however, is unable to give rise to the conduction axis, which arises from an anomalous node formed at the site of union between the scooped-out ventricular septum and the atrioventricular junction (red star with white borders).</p>
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<p>As shown in these images, all channels between the ventricles can be described as being perimembranous (<b>A</b>) when there is fibrous continuity between the leaflets of the mitral and tricuspid valves as part of the margin of the defect, muscular (<b>B</b>) when the defect has exclusively muscular rims as seen from the right ventricle, or juxta-arterial (<b>C</b>) when the defect is roofed by an area of fibrous continuity between the leaflets of the arterial valves, or in the presence of a common arterial trunk by the leaflets of the truncal valve.</p>
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<p>In this heart, showing the right-sided chambers viewed from their right side, the parietal walls of the right atrium and ventricle have been removed to show the septal surfaces. The site of the atrioventricular conduction axis can be predicted with accuracy by drawing a line from the apex of the triangle of Koch, under the inferior margin of the membranous septum, to the site of the medial papillary muscle of the tricuspid valve. The triangle of Koch is delimited by the tendon of Todaro, the continuation intramyocardially of the commissure between the Eustachian and Thebesian valves, and the hinge of the septal leaflet of the tricuspid valve. As shown by the red star with white borders, the atrioventricular node is located in the apex of the triangle. The ventricular component of the conduction axis is then sandwiched between the base of the membranous septum and the crest of the muscular ventricular septum. The right bundle branch emerges as a narrow cord in the environs of the medial papillary muscle. This knowledge, combined with information regarding the phenotypes of ventricular septal defects, permits an accurate estimation of the likely site of the atrioventricular conduction axis (see <a href="#jpm-15-00102-f006" class="html-fig">Figure 6</a>).</p>
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<p>The drawings show how, based on knowledge of the normal arrangement of the atrioventricular conduction axis (see <a href="#jpm-15-00102-f005" class="html-fig">Figure 5</a>), it is possible with accuracy to predict the location of the axis when ventricular septal defects are either perimembranous (<b>A</b>), muscular (<b>B</b>), or juxta-arterial (<b>C</b>). On occasion, however, the juxta-arterial defects can extend to become perimembranous. In the latter eventuality, the conduction axis will be at risk in the postero-inferior margin of the defect, as shown in (<b>A</b>).</p>
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<p>The images show two defects opening to the inlet of the right ventricle with unexpected locations of the atrioventricular conduction axis. (<b>A</b>) shows an atrioventricular septal defect with exclusive ventricular shunting, with (<b>B</b>) showing the arrangement found when there is straddling of the tricuspid valve.</p>
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<p>The images show the features of defects as seen in the setting of tetralogy of Fallot, which is characterised by malalignment between the muscular outlet, or conal, septum relative to the crest of the muscular ventricular septum. In (<b>A</b>), part of the border of the defect to be closed by the surgeon, shown by the dashed black line, is formed by fibrous continuity between the leaflets of the mitral and tricuspid valves, making the defect perimembranous. As was shown in <a href="#jpm-15-00102-f006" class="html-fig">Figure 6</a>B, the conduction axis in this setting will be at risk in the postero-inferior margin of such a defect. In (<b>B</b>), again with malalignment between the outlet septum and the apical muscular septum, the defect to be closed by the surgeon has exclusively myocardial rims due to fusion between the caudal limb of the septomarginal trabeculation and the ventriculo-infundibular fold. The muscle bar thus formed protects the atrioventricular conduction axis.</p>
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<p>(<b>A</b>) shows the aortic root opened through the left coronary sinus and spread to provide the typical view as seen by the morphologist. The boundaries of the root are delimited by the proximal and distal extents of the semilunar lines of attachment of the flaps that, during the cardiac cycle, open and close to guard the exit from the left ventricle. (<b>B</b>) is an enlargement of the distal extent of two of the hingelines. The arcs of the hingelines come together at the sinutubular junction to form a point. This point is usually described as the valvar commissure. If named on the basis of the dictionary definition, it would be described as a “cusp” (see text for discussion).</p>
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<p>The panels shows the arrangements of the aortic (<b>A</b>) and the pulmonary (<b>B</b>) roots having removed the larger portions of the components that open and close so as to guard the ventricular exits. It is the distal and proximal extents of the semilunar hingelines of the moving components of the valvar complexes that mark the boundaries of the roots. In the aortic root, which has been opened by making a cut through the left coronary aortic sinus, the nadirs of the hinges of moving parts supported by the sinuses which give rise to the coronary arteries sequester small crescents of myocardium at the bases of both sinuses (<b>A</b>). This formation of myocardial crescents is much more obvious in the pulmonary root, where the crescents are formed at the bases of all three valvar sinuses (<b>B</b>). This means that, in the pulmonary root, it is possible to recognise a discrete junction between the infundibular myocardium and the arterial walls of the valvar sinuses. In the aortic root, such myocardial-arterial junctions are found only at the bases of the sinuses giving rise to the coronary arteries.</p>
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<p>These panels show three views of the intact aortic root, producing images more comparable to those seen by diagnosticians (see <a href="#jpm-15-00102-f012" class="html-fig">Figure 12</a>). In (<b>A</b>), the view shows the closed leaflets of the aortic valve as seen from beneath. When seen from this aspect, the ventricular surfaces of the closed leaflets bear a significant resemblance to the cusps of the molar and premolar teeth. In (<b>B</b>), dissection to remove the walls of the left coronary and non-coronary valvar sinuses reveals the overall crown-like configuration of the root. (<b>C</b>) is prepared by photographing the closed valve from the arterial aspect, having transected the root at the level of the sinutubular junction. It shows the zones of apposition between the closed leaflets, which extend from the so-called valvar “commissures” to the centroid of the closed valvar orifice.</p>
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<p>(<b>A</b>) shows a three-dimensional reconstruction of the aortic root using a computed tomographic dataset of a normal individual. The interleaflet triangles have been segmented, along with the myocardial crescents at the bases of the valvar sinuses which give rise to the coronary arteries. The planes of the sinutubular junction and the virtual basal ring have also been segmented. (<b>B</b>) shows a two-dimensional section of a different computed tomographic dataset taken through the non-coronary sinus. It shows the detailed metrics that can now be taken for the purposes of repair of diseased aortic roots.</p>
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<p>The panels show how the malformed aortic root is best described according to the number of its sinuses, with the skirt of persisting leaflet tissue effectively producing a bileaflet or unileaflet arrangement according to the number of zones of apposition within the skirt that extend to reach the sinutubular junction. (<b>A</b>) shows the so-called “unicuspid and unicommissural arrangement”, which is built on a trisinuate scaffold. (<b>B</b>) shows the classical bicuspid variant, with fusion of the leaflets supported by the two valvar sinuses giving rise to the coronary arteries. This variant is also trisinuate. (<b>C</b>) shows the rare variant in which each leaflet is supported by its own sinus, with no evidence of fusion of developmental primordiums. This variant is bileaflet and bisinuate.</p>
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15 pages, 659 KiB  
Article
Whole-Exome Sequencing Followed by dPCR-Based Personalized Genetic Approach in Solid Organ Transplantation: A Study Protocol and Preliminary Results
by Mirgul Bayanova, Aidos Bolatov, Dias Malik, Aida Zhenissova, Aizhan Abdikadirova, Malika Sapargaliyeva, Lyazzat Nazarova, Gulzhan Myrzakhmetova, Svetlana Novikova, Aida Turganbekova and Yuriy Pya
Methods Protoc. 2025, 8(2), 27; https://doi.org/10.3390/mps8020027 - 4 Mar 2025
Viewed by 39
Abstract
Genetic profiling and molecular biology methods have made it possible to study the etiology of the end-stage organ disease that led to transplantation, the genetic factors of compatibility and tolerance of the transplant, and the pharmacogenetics of immunosuppressive drugs and allowed for the [...] Read more.
Genetic profiling and molecular biology methods have made it possible to study the etiology of the end-stage organ disease that led to transplantation, the genetic factors of compatibility and tolerance of the transplant, and the pharmacogenetics of immunosuppressive drugs and allowed for the development of monitoring methods for the early assessment of allograft rejection. This study aims to report the design and baseline characteristics of an integrated personalized genetic approach in solid organ transplantation, including whole-exome sequencing (WES) and the monitoring of dd-cfDNA by dPCR. Preliminary results reported female recipients with male donors undergoing two pediatric and five adult kidney and three heart transplantations. WES revealed a pathogenic mutation in RBM20 and VUS in TTN and PKP2 in heart recipients, while kidney donors presented mutations in UMOD and APOL1 associated with autosomal-dominant kidney diseases, highlighting the risks requiring the long-term monitoring of recipients, donors, and their family members. %dd-cfDNA levels were generally stable but elevated in cadaveric kidney recipient and one pediatric patient with infectious complications and genetic variants in the ABCB1 and ABCC2 genes. These findings highlight the potential of combining genetic and molecular biomarker-based approaches to improve donor–recipient matching, predict complications, and personalize post-transplant care, paving the way for precision medicine in transplantation. Full article
(This article belongs to the Section Omics and High Throughput)
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<p>Study design.</p>
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35 pages, 5145 KiB  
Review
The Complexity of Malignant Glioma Treatment
by Linde F. C. Kampers, Dennis S. Metselaar, Maria Vinci, Fabio Scirocchi, Sophie Veldhuijzen van Zanten, Matthias Eyrich, Veronica Biassoni, Esther Hulleman, Michael Karremann, Wilfried Stücker and Stefaan W. Van Gool
Cancers 2025, 17(5), 879; https://doi.org/10.3390/cancers17050879 - 4 Mar 2025
Viewed by 63
Abstract
Malignant glioma is a highly aggressive, therapeutically non-responsive, and deadly disease with a unique tumor microenvironment (TME). Of the 14 currently recognized and described cancer hallmarks, five are especially implicated in malignant glioma and targetable with repurposed drugs: cancer stem-like cells, in general, [...] Read more.
Malignant glioma is a highly aggressive, therapeutically non-responsive, and deadly disease with a unique tumor microenvironment (TME). Of the 14 currently recognized and described cancer hallmarks, five are especially implicated in malignant glioma and targetable with repurposed drugs: cancer stem-like cells, in general, and glioma stem-like cells in particular (GSCs), vascularization and hypoxia, metabolic reprogramming, tumor-promoting inflammation and sustained proliferative signaling. Each hallmark drives malignant glioma development, both individually and through interactions with other hallmarks, in which the TME plays a critical role. To combat the aggressive malignant glioma spatio-temporal heterogeneity driven by TME interactions, and to overcome its therapeutic challenges, a combined treatment strategy including anticancer therapies, repurposed drugs and multimodal immunotherapy should be the aim for future treatment approaches. Full article
(This article belongs to the Section Tumor Microenvironment)
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<p>Top: An overview of the main contributing factors to the 14 hallmarks of cancer [<a href="#B1-cancers-17-00879" class="html-bibr">1</a>,<a href="#B2-cancers-17-00879" class="html-bibr">2</a>,<a href="#B3-cancers-17-00879" class="html-bibr">3</a>]. In green, the first hallmarks described. In yellow, hallmarks recognized and added in 2011. In blue, four additional hallmarks added in 2022. Legends on the lower left and right side indicate cell types, cytokines, chemokines, growth factors, and other factors vital in tumor development. Dark brown cells of irregular shapes represent tumor cells. Each hallmark has been given an icon, indicated by the numbered images in circles at the end of each hallmark pie slice. These icons will be used to indicate each hallmark in further figures.</p>
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<p>A simplified overview of the effect of glioma stem cells. GSCs can self-renew, differentiate and dedifferentiate to different GBM cell types (red arrows). This can be caused by RT or CTx (TMZ) treatment (red bold arrows). Antidepressants can inhibit GSC plasticity. GSCs rely on a permissive TME (black arrows).</p>
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<p>A simplified overview of the effects of hypoxia in GBM. GBM Effects are displayed with red arrows, treatment options are shown in bright green. Hypoxia normally leads to autophagy (black arrow) which inhibits the effects of RT and CTx such as TMZ. Chloroquine treatment can inhibit autophagy. Bevacizumab inhibits angiogenesis factor VEGF. Hypoxia also includes upregulation of HIF-1α, which inhibits both CTx effects and the OXPHOS pathway, driving cellular metabolism toward anaerobic fermentation. Mebendazole and melatonin can be used to normalize HIF-1α expression levels.</p>
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<p>A simplified overview of metabolic reprogramming in GBM. Normal pathway steps are depicted with black arrows, GBM pathway steps are shown in red. Possible treatment options are depicted in bright green. Glucose is processed through glycolysis to intermediates, ATP and NADH. In cancer cells, an increase in pyruvate dehydrogenase kinase (PDK) inhibits aerobic respiration, favoring an anaerobic fermentation pathway instead. Lactic acid production leads to the acidification of the TME. Treatment with lipoic acid inhibits PDK. Metformin can then be used to inhibit the OXPHOS pathway in all fast-growing cells, specifically targeting tumor cells. Combining TMZ with Metformin treatment can revert chemoresistance.</p>
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<p>A simplified overview of the effects of immune response inflammation in GBM. Tumor-specific occurrences are indicated with red arrows, possible treatment options and effects in bright green. Downregulation (downward black arrows) of cell types or cytokines is highlighted in red, and upregulation (upward black arrows) is highlighted in orange. Due to TME acidification, M2 Macrophages and GAMs are upregulated, which inhibits cytotoxic T cell response but increases inflammation-regulating cytokines, developing into an immunosuppressive TME. Especially the upregulation of TGF-β, by both tumor-associated macrophages as well as TCA cycle mutations, further inhibits the innate and adaptive immune system. TCA cycle mutations can be halted with ONC201 treatment, isoselective inhibitors and peptide vaccines. GAMs, especially when derived from bone marrow, also aid angiogenesis. PDL1+ M2 Macrophages target CD8+ T cells via the apoptotic TRAIL pathway, both during CD8+ T cell priming and effector function. Using anti-PDL1 checkpoint inhibitors, this PD1-independent immunosuppression can be inhibited.</p>
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<p>A simplified overview of the effects of the neuron-glioma interactions. The interactions between presynaptic neurons and postsynaptic gliomas drive tumor development through AMPA postsynaptic currents, paracrine signaling factors, or GABAergic synaptic communication. The first can be inhibited with perampanel and the last one with levetiracetam.</p>
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<p>Single-cell RNA and protein analysis of myeloid cells in the pontine region of syngeneic allograft mouse models for DMG, indicating PDL1 expression in GAMs compared to healthy cells. Color scales indicate expression levels. Red circles indicate the different tumor–associated grouped cells.</p>
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<p>Example of temporal occurrence of individual tumor hallmarks during tumor development, from stage I, Tumorigenesis to stage IV, Invasion. Included is a temporal tumor treatment plan, to combat specific tumor hallmarks throughout malignancy development.</p>
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<p>Overview of possible combination strategy trajectory, separated into three treatment phases that allow for adaptation and optimal patient-individualized treatment, based on tumor status and activity. GBM leads to symptoms (indicated as a stethoscope) and suppresses the immune system. Three subsequent treatment phases are proposed to combat the initial tumor and its escape mechanisms, by temporal targeting both, the tumor directly, and its TME. The gray–red–yellow–green background colors reflect treatment effectivity as increased tumor control, also shown as tumor dedifferentiation and size decrease at the top of the figure. Yellow tumor cells represent glioma stem cells, tumor cells in variations of brown (light to dark) represent tumor cells of a different subtype, indicating here how a tumor of a different variation might grow after initial treatment of the main tumor subtype present, and how treatment might push further tumor differentiation.</p>
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20 pages, 4034 KiB  
Article
Immunomodulation of Glycyrrhiza Polysaccharides In Vivo Based on Microbiome and Metabolomics Approaches
by Yixuan Wu, Jie Sun, Wenjie Xie, Simin Xue, Xinli Li, Jianming Guo, Jinjun Shan, Guoping Peng and Yunfeng Zheng
Foods 2025, 14(5), 874; https://doi.org/10.3390/foods14050874 - 4 Mar 2025
Viewed by 35
Abstract
Glycyrrhiza uralensis Fisch. is a medicinal herb that can be added to food to provide therapeutic effects and reduce the burden of medications. Herein, the immunomodulatory effects of Glycyrrhiza polysaccharides (GPs) were verified and illustrated by intervening immunocompromised rats treated with different doses [...] Read more.
Glycyrrhiza uralensis Fisch. is a medicinal herb that can be added to food to provide therapeutic effects and reduce the burden of medications. Herein, the immunomodulatory effects of Glycyrrhiza polysaccharides (GPs) were verified and illustrated by intervening immunocompromised rats treated with different doses of GPs, which were reflected for adjusting the composition and structure of the intestinal microbiota and altering the metabolic profile. The immunomodulatory effects of GPs were exerted by regulating the intestinal microenvironment. In particular, GPs could promote the growth of probiotic bacteria Allobaculum, norank__o_Clostridia_UCG-014, Dubosiella, and g__norank_o___RF39 and curb the growth of harmful bacteria Enterococcus. The results showed that GPs had a prebiotic effect, which contributed to improving the intestinal environment and maintaining intestinal health. In addition, the content of beneficial differential metabolites was up-regulated, especially short-chain fatty acids, with alanine, aspartate, and glutamate metabolism; arginine biosynthesis; glyoxylate and dicarboxylate metabolism being the most enriched pathways. These metabolic pathways imply the metabolic process of GPs, and the metabolic pathways and differential effector metabolites of it are focused. Overall, the purpose of this article lies in providing support for the application of GPs for regulating immune function. Full article
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<p>Chemical characterization of GPs. (<b>A</b>) High-performance gel permeation chromatography profiles of GPs on a TSK gel PW<sub>XL</sub> 3000 column. (<b>B</b>) Molecular weight (lg M<sub>W</sub>) vs. retention time (Rt) curves. (<b>C</b>,<b>D</b>) Monosaccharide profiles of standards and GPs by HPLC-PDA: (1) rhamnose, (2) galacturonic acid, (3) glucose, (4) galactose, and (5) arabinose. (<b>E</b>) FT-IR spectrum. (<b>F</b>) SEM images of GPs at different magnifications.</p>
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<p>GPs improved the organ index, immune index, and inflammatory cytokine secretion in immunocompromised rats. (<b>A</b>) Body weight, (<b>B</b>) spleen index, (<b>C</b>) thymus index, (<b>D</b>) IL-10, (<b>E</b>) IFN-γ, (<b>F</b>) IgG, (<b>G</b>) IL-2, and (<b>H</b>) IL-6. Data were expressed as mean ± standard deviation (<span class="html-italic">n</span> = 6). *** <span class="html-italic">p</span> &lt; 0.001 vs. the control group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span>&lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. the model group.</p>
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<p>GPs helped to lessen spleen and intestinal damage in rats with impaired immune systems. (<b>A</b>) The spleen underwent H&amp;E staining. (<b>B</b>) Immunofluorescence of occludin in the intestinal issues. (<b>C</b>) Immunofluorescence of ZO-1 in the intestinal issues. (<b>D</b>) Statistical graph of occludin. (<b>E</b>) Statistical graph of ZO-1. Data are expressed as mean ± standard deviation (<span class="html-italic">n</span> = 3). *** <span class="html-italic">p</span> &lt; 0.001 vs. the control group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. the model group.</p>
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<p>GPs regulated the gut microbial diversity in immunocompromised rats. (<b>A</b>) Ace index. (<b>B</b>) Simpson index. (<b>C</b>) Sobs index (<b>D</b>) Firmicutes/Bacteroidetes ratio. (<b>E</b>) PCA analysis. (<b>F</b>) Multi-group test of variance. (<b>G</b>) Phylum-level community barplot analysis. (<b>H</b>) Genus-level community barplot analysis. (<b>I</b>–<b>L</b>) LEfSe analysis between two different groups. (<b>M</b>–<b>Q</b>) Relative abundance of <span class="html-italic">Enterococcus</span>, <span class="html-italic">Allobaculum</span>, <span class="html-italic">norank_o__Clostridia_UCG-014</span>, <span class="html-italic">Dubosiella,</span> and <span class="html-italic">norank_o_RF39</span> in different groups. Data are displayed as mean ± standard deviation (<span class="html-italic">n</span> ≥ 3). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. the control group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. the model group.</p>
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<p>Untargeted metabolomics analysis of serum metabolites in rats. (<b>A</b>–<b>D</b>) OPLS-DA score scatter plot of serum metabolites (<span class="html-italic">n</span> = 7). (<b>E</b>–<b>H</b>) Volcano plot of differential metabolites (<span class="html-italic">n</span> = 7). The green dots indicate down-regulated metabolites, and the red dots indicate up-regulated metabolites (<span class="html-italic">p</span> &lt; 0.05, FC &gt; 1.5, FC &lt; 0.67, and VIP &gt; 1). (<b>I</b>–<b>L</b>) KEGG pathway analysis between two different groups.</p>
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<p>The concentration of SCFAs in rat fecal and serum samples in different groups. (<b>A</b>–<b>D</b>) SCFAs in fecal. (<b>E</b>–<b>H</b>) SCFAs in serum. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 vs. the control group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 vs. the model group.</p>
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<p>Correlation analysis between dominant gut microbiota with differential metabolites (CON vs. MOD). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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8 pages, 725 KiB  
Article
A Single-Center Experience of En Bloc vs. Single Renal Transplantation on Adult Recipients
by Yoon-Jung Chang, Samuel Simpson, Megan Charette and Obi Ekwenna
Transplantology 2025, 6(1), 7; https://doi.org/10.3390/transplantology6010007 - 4 Mar 2025
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Abstract
Background/Objectives: While there are several debates on en bloc renal transplants and pediatric donors regarding the efficacy and concern for renal mass, multiple studies have supported the notion that transplanting pediatric en bloc kidneys produces comparable results in contrast to single kidneys [...] Read more.
Background/Objectives: While there are several debates on en bloc renal transplants and pediatric donors regarding the efficacy and concern for renal mass, multiple studies have supported the notion that transplanting pediatric en bloc kidneys produces comparable results in contrast to single kidneys from living or deceased donors. Methods: This case series included a retrospective analysis of a university medical center, primarily focused on comparing the post-operative outcomes between recipients of pediatric and adult en bloc kidneys, which are horseshoe kidneys, from deceased donors and recipients of single adult kidneys from living or deceased donors. Results: This study demonstrated that the post-operative results in recipients of pediatric en bloc kidneys consisting of serum creatinine and estimated glomerular filtration rate (eGFR) values were lower and higher, respectively, and had a comparable improvement in kidney function at post-transplant, 1-week, 1-month, 3-months, and 1-year post-op marks. Conclusions: Our center data and outcomes indicate that en bloc kidney transplantation from pediatric donors yields comparable results to that of single kidney transplantations from living and deceased donors. Full article
(This article belongs to the Section Solid Organ Transplantation)
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<p>(<b>a</b>) Primary renal diseases of pediatric en bloc kidney recipients at this center; (<b>b</b>) primary renal diseases of adult kidney recipients at this center.</p>
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<p>(<b>a</b>) Serum creatinine levels of pediatric en bloc vs. single kidney transplantation on adult recipients at the post-transplant, 1-week, 1-month, 3-months, and 1-year marks; (<b>b</b>) eGFR levels of pediatric en bloc vs. single kidney transplantation on adult recipients at the post-transplant, 1-week, 1-month, 3-months, and 1-year marks.</p>
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13 pages, 1801 KiB  
Article
Concordance of Helicobacter pylori Detection Methods in Symptomatic Children and Adolescents
by Camila Cabrera, Yanira Campusano, Joaquín Torres, Dinka Ivulic, Valeria Galvez, Diego Tapia, Vicente Rodríguez, Anne Lagomarcino, Alejandra Gallardo, Francisco Alliende, Marcela Toledo, Gabriela Román, Francisca Jaime, Mónica González, Pamela Marchant, Marianela Rojas, Juan Ignacio Juanet, Mónica Villanueva, Juan Cristobal Ossa, Felipe Del Canto, Tomeu Viver, Miguel O’Ryan and Yalda Luceroadd Show full author list remove Hide full author list
Microorganisms 2025, 13(3), 583; https://doi.org/10.3390/microorganisms13030583 - 4 Mar 2025
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Abstract
Background: Helicobacter pylori is the most prevalent chronic bacterial infection globally, acquired mostly during childhood. It is associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Due to challenges in culturing H. pylori, diagnostic reference standards often rely on combining ≥2 [...] Read more.
Background: Helicobacter pylori is the most prevalent chronic bacterial infection globally, acquired mostly during childhood. It is associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Due to challenges in culturing H. pylori, diagnostic reference standards often rely on combining ≥2 non-culture, biopsy-based methods. Histology with Giemsa staining is widely used in clinical settings due to its low cost and reliable performance. Methods: This study evaluated the concordance between histology with Giemsa staining as the reference standard and other diagnostic methods, including the rapid urease test (RUT), ureA RT-PCR, 16S sequencing, and anti-H. pylori serum IgG. Positive percent of agreement (PPA), negative percent of agreement (NPA) and concordance kappa index were calculated. Results: A total of 120 patients (41 positive and 79 negative by Giemsa staining) were analyzed. Among the methods tested, RT-PCR for ureA showed the best performance (PPA = 94.7%, NPA = 98.6%, kappa = 0.939), while RUT underperformed compared with expectations (PPA = 65.9%, NPA = 97.5%, kappa = 0.681). Serology had the lowest performance (PPA = 53.7%, NPA = 96.1%, kappa = 0.548). Conclusions: The combination of histology with Giemsa staining and ureA RT-PCR achieved the highest detection rate and strongest agreement. Full article
(This article belongs to the Special Issue Helicobacter pylori Infection: Detection and Novel Treatment)
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<p>Flow chart of sample processing.</p>
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<p>Results for <span class="html-italic">H. pylori</span> detection for each method by patient. All the positive samples for <span class="html-italic">H. pylori</span> are in purple. ND: Not determined.</p>
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<p>Venn diagram illustrating the positive agreement between histology with Giemsa staining of gastric mucosa samples and other diagnostic methods. (<b>A</b>) Comparison of gastric histology with ureA RNA detection by RT-qPCR in gastric samples. (<b>B</b>) Comparison of gastric histology with H. pylori detection by 16S rRNA amplification and sequence analysis. (<b>C</b>) Comparison of gastric histology with urease activity detection using the Rapid Urease Test (RUT). (<b>D</b>) Comparison of gastric histology with IgG anti-H. pylori detection in serum by ELISA.</p>
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14 pages, 2957 KiB  
Article
A Novel Rapid Detection Method for Mycobacterium tuberculosis Based on Scattering-Light Turbidity Using Loop-Mediated Isothermal Amplification
by Meimei Zeng, Xinru Wang, Zifeng Tan, Wenyan Guo, Yan Deng, Song Li, Libo Nie, Nongyue He and Zhu Chen
Biosensors 2025, 15(3), 162; https://doi.org/10.3390/bios15030162 - 3 Mar 2025
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Abstract
The accurate detection of Mycobacterium tuberculosis (MTB) is a pressing challenge in the precise prevention and control of tuberculosis. Currently, the efficiency and accuracy of drug resistance detection for MTB are low, and cross-contamination is common, making it inadequate for clinical needs. This [...] Read more.
The accurate detection of Mycobacterium tuberculosis (MTB) is a pressing challenge in the precise prevention and control of tuberculosis. Currently, the efficiency and accuracy of drug resistance detection for MTB are low, and cross-contamination is common, making it inadequate for clinical needs. This study developed a rapid nucleic acid detection method for MTB based on scattering loop-mediated isothermal amplification (LAMP). Specific primers for the MTB-specific gene (Ag85B) were designed, and the LAMP reaction system was optimized using a self-developed scattering LAMP turbidimeter. Experimental results showed that the optimal reaction system included 1.5 µL of 100 mmol/L magnesium ions, 3.5 µL of 10 mmol/L dNTPs, 6 µL of 1.6 mol/L betaine, and a reaction temperature of 65 °C. The minimum detection limit was 12.40 ng/L, with the fastest detection time being approximately 10 min. The reaction exhibited good specificity, with no amplification bands for other pathogens. Twenty culture-positive samples and twenty culture-negative samples were tested in parallel; the accuracy of the positive group was 100%, the detection time was (24.9 ± 13 min), and there was no negative detection. This method features high detection efficiency, low cost, high accuracy, and effectively reduces cross-contamination, providing a new technology for the rapid clinical detection of MTB. Full article
(This article belongs to the Section Biosensor Materials)
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<p>Reaction device setup: (<b>a</b>) The laser emits red light with a wavelength of 650 nm and a power of 0.2 W, transmitted through the incident optical fiber to the reaction device; (<b>b</b>) MTB samples obtained from the hospital undergo nucleic acid extraction to obtain DNA, which is then mixed with the LAMP reaction system and placed in the reaction well; (<b>c</b>) the heating plate is used to raise the temperature of the reaction well to 65 °C, initiating the LAMP reaction; (<b>d</b>) the output optical fiber transmits scattered light from the LAMP reaction system to the photodetector on the circuit board, where the signal is filtered and amplified; (<b>e</b>) the data acquisition card collects the voltage signal; (<b>f</b>) the computer collects the turbidity data for analysis. The data are plotted using Origin to obtain the reaction results.</p>
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<p>Temperature optimization: (<b>A</b>) turbidity scatter plots at different temperatures; (<b>B</b>) electrophoresis of amplification products with M-DNA marker: 1—63 °C, 2—64 °C, 3—65 °C, 4—66 °C, 5—negative control; (<b>C</b>) precipitate from the 65 °C amplification reaction.</p>
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<p>Optimization of different reagents: (<b>A</b>) turbidity scatter plots at different volumes of magnesium ion solution; (<b>B</b>) electrophoresis of amplification products with M-DNA marker: 1—0.5 µL magnesium ion, 2—1.5 µL magnesium ion, 3—2.5 µL magnesium ion, 4—3.5 µL magnesium ion, 5—negative control; (<b>C</b>) turbidity scatter plots at different volumes of dNTP solution. Scattering values and electrophoresis of different volumes of dNTP solution; (<b>D</b>) electrophoresis of amplification products with M-DNA marker: 1—1.5 µL dNTPs, 2—2.5 µL dNTPs, 3—3.5 µL dNTPs, 4—4.5 µL dNTPs, 5—negative control; (<b>E</b>) turbidity scatter plots at different volumes of betaine solution; (<b>F</b>) electrophoresis of amplification products with M-DNA marker: 1—4 µL betaine, 2—6 µL betaine, 3—8 µL betaine, 4—10 µL betaine, 5—negative control.</p>
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<p>Real-time turbidity LAMP specificity detection and electrophoresis: (<b>A</b>) turbidity scatter plots for different kinds of DNA templates; (<b>B</b>) electrophoresis of amplification products with M-DNA marker: 1—MTB, 2—<span class="html-italic">Pseudomonas aeruginosa</span>, 3—<span class="html-italic">Escherichia coli</span>, 4—<span class="html-italic">Helicobacter pylori</span>, 5—<span class="html-italic">Staphylococcus aureus</span>, 6—negative control.</p>
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<p>(<b>A</b>) Real-time turbidity LAMP sensitivity detection; (<b>B</b>) linear relationship between DNA concentration and TTR; (<b>C</b>) linear relationship between DNA concentration and CT number.</p>
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<p>(<b>A</b>) Amplification lift time within 60 min for positive and negative samples. The scattered voltage of 20 positive samples reached the threshold value, and 20 negative samples did not reach the threshold value, TTR = 0. (<b>B</b>) Results of LAMP and <span class="html-italic">Mycobacterium tuberculosis</span> culture for 40 samples. The experimental results were consistent with those of the mycobacterium tuberculosis culture method.</p>
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16 pages, 1476 KiB  
Article
Gut Microbiota Alteration in Healthy Preterm Infants: An Observational Study from Tertiary Care Center in India
by Prabavathi Devarajalu, Jogender Kumar, Sourabh Dutta, Savita Verma Attri and Jayakanthan Kabeerdoss
Microorganisms 2025, 13(3), 577; https://doi.org/10.3390/microorganisms13030577 - 3 Mar 2025
Viewed by 137
Abstract
Various prenatal and postnatal factors such as gestational age, mode of delivery, sex, antibiotic exposure, feeding type, duration of feed and other exposures associated with the hospital environment can drive the formation of gut microbiota. In the current study, we examined the role [...] Read more.
Various prenatal and postnatal factors such as gestational age, mode of delivery, sex, antibiotic exposure, feeding type, duration of feed and other exposures associated with the hospital environment can drive the formation of gut microbiota. In the current study, we examined the role of all these factors in the gut microbiota of healthy Indian preterm infants admitted to NICU in the first four weeks of life. Preterm neonates admitted to the NICU from April 2023 and October 2023 were recruited and fecal samples were collected weekly once beginning from the seventh day till the 30th day of life. 16s rRNA gene sequencing was performed on the NovaSeq 6000 platform. The PICRUSt2 tool was used to predict the functional profiles of the gut microbiome. A total of 61 samples were collected from 16 preterm infants. Alpha and beta diversity showed the administration of probiotics, postnatal age, mode of delivery, and sex of infants as major contributors to altered microbial diversity in preterm infants. The MaAsLin2 analysis showed that the supplementation of probiotics increased Bifidobacterium levels. PICRUSt2 analysis revealed that probiotic supplementation increased the bacterial genes responsible for bile acid metabolism and glycosphingolipid synthesis. Probiotics and postnatal age are responsible for alterations of the gut microbial composition in healthy preterm infants. Full article
(This article belongs to the Section Gut Microbiota)
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<p>Alpha diversity metrics: (<b>a</b>) observed ASVs and (<b>b</b>) Shannon index in first four weeks of preterm infants.</p>
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<p>(<b>a</b>) Observed ASVs and (<b>b</b>) Shannon index on samples before and after probiotics supplementation.</p>
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<p>(<b>a</b>) Observed ASVs and (<b>b</b>) Shannon index on samples based on sex.</p>
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<p>Nonmetric multidimensional scaling (NMDS) plot generated based on Bray–Curtis distance. Each sample represents a dot. (<b>a</b>) Colored according to weeks. (<b>b</b>) Preterm. (<b>c</b>) Birth weight. (<b>d</b>) Mode of delivery. (<b>e</b>) Sex. (<b>f</b>) Probiotics.</p>
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<p>Nonmetric multidimensional scaling (NMDS) plot generated based on Bray–Curtis distance. Each sample represents a dot. (<b>a</b>) Colored according to weeks. (<b>b</b>) Preterm. (<b>c</b>) Birth weight. (<b>d</b>) Mode of delivery. (<b>e</b>) Sex. (<b>f</b>) Probiotics.</p>
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<p>LEfSe analysis identified differential microbial abundance between samples collected before and after probiotic supplementation.</p>
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<p>Bar plot depicting significant metabolic pathways identified by functional prediction analysis in samples of probiotic supplementation compared to non-supplemented samples. Grey color represents confidence interval.</p>
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12 pages, 542 KiB  
Article
Association of COVID-19 Pandemic with Newly Diagnosed Anorexia Nervosa Among Children and Adolescents in Japan
by Yoshifumi Fukuya, Keitaro Miyamura, Tomoyuki Funatogawa, Taiju Yamaguchi, Naoyuki Katagiri and Takahiro Nemoto
Medicina 2025, 61(3), 445; https://doi.org/10.3390/medicina61030445 - 3 Mar 2025
Viewed by 225
Abstract
Background and Objectives: The COVID-19 pandemic globally has negative effects on mental health. Research from Western countries, such as the US, Canada, Australia, and Europe, shows that the COVID-19 pandemic is associated with an increased trend of anorexia nervosa (AN) among children [...] Read more.
Background and Objectives: The COVID-19 pandemic globally has negative effects on mental health. Research from Western countries, such as the US, Canada, Australia, and Europe, shows that the COVID-19 pandemic is associated with an increased trend of anorexia nervosa (AN) among children and adolescents. However, the trend after the pandemic in Eastern countries, including Japan, is not well-understood, and it remains unclear whether the pandemic is associated with the trend in these countries. This study aimed to examine the association between the COVID-19 pandemic and the newly diagnosed AN among children and adolescents in Japan. Materials and Methods: Using the nationwide multi-hospital database in Japan, we analyzed the clinical outpatient data in the departments of pediatrics, psychosomatic medicine, and psychiatry. The participants comprised children and adolescents aged 7–19 years newly diagnosed with AN from January 2017 to January 2022. An interrupted time series analysis was used to compare the trends of newly diagnosed AN before and after the COVID-19 pandemic. Estimating the changes in the trends over the pandemic was performed using a Poisson regression model. Results: The total cases of newly diagnosed AN were 41 cases diagnosed in 38 months (1.08 cases per month) before the pandemic and 34 in 23 months (1.48 cases per month) after the pandemic. Notably, in the 7–14 age group, the cases per month increased from 0.74 to 1.13 cases per month over the period. Before the pandemic, a decrease in cases was observed (Incidence Rate Ratio [IRR] = 0.961; 95% CI = 0.932–0.990). Conversely, the after-pandemic period showed a contrasting trend, with increased cases (IRR = 1.096; 95% CI = 1.032–1.176). Furthermore, the number and cases per month in boys increased over the period, from 1 to 5 cases and from 0.03 to 0.22 cases per month, compared to girls from 28 to 26 cases and from 1.05 to 1.26 cases per month. Conclusions: Our findings suggest that sociocultural differences at a national level may not affect the trend of AN after the pandemic. The pandemic and lifestyle changes after the pandemic occurred in both Western and Eastern countries. Considering that, individual, parental, and peer factors related to the pandemic and the consequent lifestyle changes may be more associated with the development of AN. Further research in different countries is needed to elucidate the mechanisms of AN and the long-term impact of the pandemic. Full article
(This article belongs to the Section Psychiatry)
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<p>Trends in newly diagnosed cases of AN aged 7–19 years. The short-dashed line indicates the period of school closure, March 2020. The dashed line shows the counterfactual trend after the COVID-19 pandemic.</p>
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9 pages, 207 KiB  
Article
Predictive Factors of Persistent Growth Hormone Deficiency and Impact on Final Height
by Flavia Urbano, Mariangela Chiarito, Luigi Antonio Moscogiuri, Crescenza Lattanzio, Rossella Vitale, Orazio Valerio Giannico, Gabriele Annesi, Clara Zecchino and Maria Felicia Faienza
Children 2025, 12(3), 324; https://doi.org/10.3390/children12030324 - 3 Mar 2025
Viewed by 172
Abstract
Background/Objectives: Recombinant growth hormone (rhGH) treatment plays an important role in the transition phase in those subjects diagnosed as having persistent growth hormone deficiency (GHD). We aimed to identify the main predictors of persistent GHD in a large cohort of subjects with childhood-onset [...] Read more.
Background/Objectives: Recombinant growth hormone (rhGH) treatment plays an important role in the transition phase in those subjects diagnosed as having persistent growth hormone deficiency (GHD). We aimed to identify the main predictors of persistent GHD in a large cohort of subjects with childhood-onset GHD who underwent retesting and their correlation with height gain and mid-parental height (MPH). Methods: Anthropometric data, such as growth rate; bone age (BA); IGF-1 SDS at the start, at 1 year, and at the end of rhGH therapy; GH peak at diagnosis and at retesting; brain Magnetic Resonance Imaging (MRI) at diagnosis; and height gain upon reaching final height (FH) and compared to MPH, were obtained from medical records of GHD patients. Results: Persistent GHD was detected in 37 out of 91 (40.7%) GHD subjects. In univariate analysis, persistent GHD was associated with growth rate at 1 year (p = 0.0117) and with the first test GH peak (p = 0.0290). In the regression analysis, persistent GHD was positively associated with growth rate at 1 year (p = 0.0294) and negatively with female gender (p = 0.0424). Height gain was positively associated with growth rate (p = 0.0010) and with age at onset (p = 0.0021), while an inverse association with BA at baseline (p = 0.0002) and IGF-1 SDS (p = 0.0321) was found. Conclusions: Our study confirmed that the most important predictor of persistent GHD is the growth rate in the first year of therapy. Furthermore, growth rate in the first year, female gender, and lower BA at diagnosis are predictors of rhGH efficacy both in terms of height gain and target height achievement. Full article
(This article belongs to the Section Pediatric Endocrinology & Diabetes)
27 pages, 255 KiB  
Article
Impact of Marital Status, Education, and Family Size on Parental Behaviors Toward Early Childhood Caries in Romania
by Abel Emanuel Moca, Ioan Andrei Țig, Jessica Olivia Cherecheș, Rahela Tabita Moca and Raluca Iurcov
Dent. J. 2025, 13(3), 111; https://doi.org/10.3390/dj13030111 - 3 Mar 2025
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Abstract
Background and Objectives: This study aimed to examine the influence of socio-demographic factors (marital status, number of children, and education level) on the knowledge, attitudes, and practices (KAP) concerning Early Childhood Caries (ECC) prevention among parents in Bihor, Romania. This research seeks [...] Read more.
Background and Objectives: This study aimed to examine the influence of socio-demographic factors (marital status, number of children, and education level) on the knowledge, attitudes, and practices (KAP) concerning Early Childhood Caries (ECC) prevention among parents in Bihor, Romania. This research seeks to address the lack of regional data on the influence of socio-demographic factors, such as marital status, number of children, and education level, on parental knowledge, attitudes, and practices regarding ECC prevention. These insights are essential for developing targeted public health interventions in Romania. Materials and Methods: Conducted from March to September 2024, this cross-sectional study utilized a KAP questionnaire distributed online to parents of children under six. The survey was adapted to local contexts and included sections on demographic data and ECC-specific knowledge, attitudes, and practices. Statistical analyses, including Chi-square tests, were performed to evaluate the relationship between socio-demographic factors and KAP outcomes, ensuring robust data interpretation under ethical standards set by the Declaration of Helsinki. Results: Of the 798 respondents who accessed the questionnaire, 419 completed it, resulting in a completion rate of 52.5%. The participants had a mean age of 33.8 years. In terms of gender distribution, 348 (83.1%) were female and 71 (16.9%) were male. Higher educational levels were strongly correlated with better ECC knowledge and preventive practices; parents with university degrees demonstrated significantly better understanding and engagement in ECC prevention (p < 0.05). Married parents participated more actively in ECC prevention than unmarried ones, with 61.1% adhering to recommended practices compared to significantly lower rates among unmarried parents (p = 0.020). While this difference was statistically significant, the lower representation of unmarried parents in the sample should be considered when interpreting this finding. Families with fewer children showed more effective ECC preventive practices (p = 0.001). Conclusions: The study suggests that higher education and smaller family sizes are associated with better ECC prevention behaviors, emphasizing the need for targeted public health interventions. These could include parental education campaigns on ECC prevention, community-based oral health workshops, subsidized fluoride programs, and increased accessibility to pediatric dental services for underprivileged families. Full article
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Article
Predicting the Effect of Meropenem Against Klebsiella pneumoniae Using Minimum Inhibitory Concentrations Determined at High Inocula
by Maria V. Golikova, Kamilla N. Alieva, Elena N. Strukova, Julia R. Savelieva, Daria A. Kondratieva, Svetlana A. Dovzhenko, Mikhail B. Kobrin, Vladimir A. Ageevets, Alisa A. Avdeeva and Stephen H. Zinner
Antibiotics 2025, 14(3), 258; https://doi.org/10.3390/antibiotics14030258 - 3 Mar 2025
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Abstract
Background/Objectives: Assessing antibiotic MICs at high bacterial counts is likely to disclose hidden bacterial resistance and the inoculum effect if present and therefore also reveal potential decreased antibiotic effectiveness. In the current study, we evaluated the predictive potential of MICs determined at high [...] Read more.
Background/Objectives: Assessing antibiotic MICs at high bacterial counts is likely to disclose hidden bacterial resistance and the inoculum effect if present and therefore also reveal potential decreased antibiotic effectiveness. In the current study, we evaluated the predictive potential of MICs determined at high bacterial inocula to evaluate meropenem effectiveness and emergence of resistance in Klebsiella pneumoniae. Methods: Nine carbapenemase-free or carbapenemase-producing K. pneumoniae strains were exposed to meropenem in an in vitro hollow-fiber infection model (HFIM). The treatment effects were correlated with simulated antibiotic ratios of the area under the concentration–time curve (AUC) to the MIC (AUC/MIC) and to MICs determined at high inocula (AUC/MICHI). Results: Based on MICs determined at standard inocula, meropenem effects at different AUC/MIC ratios for both carbapenemase-free and carbapenemase-producing K. pneumoniae strains were stratified and could not be described by a single relationship. In contrast, when AUC/MICHI ratios were used, a single relationship with the antibiotic effect was obtained for all tested strains. Similarly, the emergence of meropenem resistance in HFIM was concordant with AUC/MICHI, but not with AUC/MIC ratios. Conclusions: MICs determined at high bacterial inocula enable the prediction of meropenem effects both for carbapenemase-free and for carbapenemase-producing K. pneumoniae strains. Also, MICs at standard and high inocula can identify carbapenemase-producing strains by revealing the inoculum effect. Full article
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<p>Total and meropenem-resistant (to 2×, 4×, 8× and 16× MIC of meropenem) counts of <span class="html-italic">K. pneumoniae</span> in in vitro pharmacodynamic simulations with meropenem against carbapenemase-non-producing strains. Simulated pharmacokinetics: 2 g as a 3 h infusion every 8 h for 5 days in ELF. Arrows indicate the start of meropenem infusions.</p>
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<p>Total and meropenem-resistant (to 2×, 4×, 8× and 16× MIC of meropenem) counts of <span class="html-italic">K. pneumoniae</span> in in vitro pharmacodynamic simulations with meropenem against carbapenemase-producing strains. Simulated pharmacokinetics: 2 g as a 3 h infusion every 8 h for 5 days in ELF. The data for <span class="html-italic">K. pneumoniae</span> ATCC BAA-1904 strain are reproduced from Alieva et al. [<a href="#B16-antibiotics-14-00258" class="html-bibr">16</a>]. Arrows indicate the start of meropenem infusions.</p>
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<p>“AUC/MIC-AUBC” and “AUC/MIC<sub>HI</sub>-AUBC” relationships. (<b>a</b>) The data assembled using standard MIC values; (<b>b</b>) the data assembled using high inocula MIC values (MIC<sub>HI</sub>) and described with the sigmoid function. The data for <span class="html-italic">K. pneumoniae</span> ATCC BAA-1904 strain are reproduced from Alieva et al. [<a href="#B16-antibiotics-14-00258" class="html-bibr">16</a>].</p>
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<p>MICs at standard (MIC) and high (MIC<sub>HI</sub>) inocula and the corresponding AUBC<sub>M</sub>s (integral measure of meropenem resistance and area under the bacterial curve resistant to 4× MIC of meropenem, obtained from pharmacodynamic simulations with respective <span class="html-italic">K. pneumoniae</span> strains and meropenem). The higher the AUBC<sub>M</sub>, the more intense selection of resistance to meropenem. S, susceptible; NS, non-susceptible; R, resistant. CNP—carbapenemase-non-producing <span class="html-italic">K. pneumoniae</span> strains; KPC—KPC-producing <span class="html-italic">K. pneumoniae</span> strains. The data for <span class="html-italic">K. pneumoniae</span> ATCC BAA-1904 are reproduced from Alieva et al. [<a href="#B16-antibiotics-14-00258" class="html-bibr">16</a>].</p>
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<p>“AUC/MIC<sub>HI</sub>-AUBC” relationship described with the sigmoid function. The data for OXA-48-producing <span class="html-italic">K. pneumoniae</span> 1128, 1456, 1170 and KPC-producing ATCC BAA-1904 strains are reproduced from Alieva et al. [<a href="#B16-antibiotics-14-00258" class="html-bibr">16</a>].</p>
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<p>MICs at standard (MIC) and high (MIC<sub>HI</sub>) inocula and the corresponding AUBC<sub>M</sub>s (integral measure of meropenem resistance and area under the bacterial curve resistant to 4× MIC of meropenem, obtained from pharmacodynamic simulations with respective <span class="html-italic">K. pneumoniae</span> strains and meropenem). The higher the AUBC<sub>M</sub>, the more intense the selection of meropenem resistance. S, susceptible; NS, non-susceptible; R, resistant. CNP—carbapenemase-non-producing <span class="html-italic">K. pneumoniae</span> strains; OXA-48—OXA-48 carbapenemase-producing <span class="html-italic">K. pneumoniae</span> strains; KPC—KPC-producing <span class="html-italic">K. pneumoniae</span> strains. The data for <span class="html-italic">K. pneumoniae</span> ATCC BAA-1904 and all OXA-48-producing strains are reproduced from Alieva et al. [<a href="#B16-antibiotics-14-00258" class="html-bibr">16</a>].</p>
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<p>“AUC/MIC-AUBC<sub>M</sub>” and “AUC/MIC<sub>HI</sub>-AUBC<sub>M</sub>” relationships. (<b>a</b>) Data assembled using standard MIC values; (<b>b</b>) data assembled using high inocula MIC values (MIC<sub>HI</sub>). Data for <span class="html-italic">K. pneumoniae</span> ATCC BAA-1904 strain and all OXA-48-producing strains are reproduced from Alieva et al. [<a href="#B16-antibiotics-14-00258" class="html-bibr">16</a>].</p>
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