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The newest technology allows the medical industry to manufacture innovative products such as milled titanium prosthodontic parts in an implant for a screw-retained suprastructure. In the literature, there are some articles on the clinical usage of subperiosteal implants, but none of these publications, either in PubMed or Google Scholar, thoroughly describe the workflow for the design and manufacture of individual implants for maxillofacial surgery with milled threads for a screw-retained prosthodontic bridge. The aim of the article is to present a step-by-step method of producing personalized implants, from the first steps of production to the implantation of the final product. The article includes information on patient qualification for surgery, computational preparation and skull printing, planning of Mai Implants®, meshing, 3D printing and milling, cleaning, rinsing, anodizing, and laser marking, as well as the cleaning and sterilization process in a hospital or dental clinic. A detailed description of implant production allows for the analysis of each step and the development of technology. The production of implants is an expensive procedure, but considering all the advantages of the Mai Implants® treatment and the disadvantages of alternatives, the product is worth the price.

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This paper reports the results of our study on electrochemical polishing of titanium and a Ti-based alloy using non-aqueous electrolyte. It was shown that electropolishing ensured the removal of surface defects, thereby providing surface smoothing and decreasing surface roughness. The research was conducted using samples made of titanium and Ti6Al4V alloy, as well as implant system elements: implant analog, multiunit, and healing screw. Electropolishing was carried out under a constant voltage (10-15 V) with a specified current density. The electrolyte used contained methanol and sulfuric acid. The modified surface was subjected to a thorough analysis regarding its surface morphology, chemical composition, and physicochemical properties. Scanning electron microscope images and profilometer tests of roughness confirmed significantly smoother surfaces after electropolishing. The surface profile analysis of processed samples also yielded satisfactory results, showing less imperfections than before modification. The EDX spectra showed that electropolishing does not have significant influence on the chemical composition of the samples.

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The new Radiological Corticalization Index (CI) is an indicator that describes bone remodeling near the dental implant's neck at the pixel level and is not visible to the naked eye. The aim of this research was to evaluate the correlation between the CI and bone remodeling using only radiographic (RTG) images. RTG samples were divided into groups depending on prosthetic restoration; the implant neck area around dental implants was examined, and texture features of the RTG images were analyzed. The study also investigated the type of prosthetic restoration and its influence as a factor on bone structure. The statistical analysis included evaluating feature distribution, comparing means (t-test) or medians (W-test), and performing a regression analysis and one-way analysis of variance or the Kruskal-Wallis test, as no normal distribution or between-group variance was indicated for the significant differences in the investigated groups. Differences or relationships were considered statistically significant at p < 0.05. The research revealed correlations between single crowns, overdenture restoration, bridge restoration, platform switching, prosthetic fracture, CI, and also marginal bone loss where p was lower than 0.05. However, the corticalization phenomenon itself has not yet been fully explored. The findings suggest that, depending on the type of prosthetic restoration, the corticalization index may correlate with marginal bone loss or not. Further research is necessary, as the index is suspected to not be homogeneous.

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Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their resistance to anti-PD-L1 by enhancing its binding with PD-1 on CD8+ T cells. In orthotopic, syngeneic EOC models in female mice, inhibiting branched N-glycans using 2-Deoxy-D-glucose sensitizes HR-proficient, but not HR-deficient EOCs, to anti-PD-L1. These findings indicate branched N-glycans as promising therapeutic targets whose inhibition sensitizes HR-proficient EOCs to ICB by overcoming immune evasion.

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The study involved numerical FEA (finite element analysis) of dental implants. Based on this, fatigue tests were conducted according to the PN-EN 14801 standard required for the certification of dental products. Thanks to the research methodology developed by the authors, it was possible to conduct a thorough analysis of the impact of external and internal factors such as material, geometry, loading, and assembly of the dental system on the achieved value of fatigue strength limit in the examined object. For this purpose, FEM studies were based on identifying potential sites of fatigue crack initiation in reference to the results of the test conducted on a real model. The actions described in the study helped in the final evaluation of the dental system design process named by the manufacturer as INTEGRA OPTIMA 3.35. The objective of the research was to identify potential sites for fatigue crack initiation in a selected dental system built on the INTEGRA OPTIMA 3.35 set. The material used in the research was titanium grade 4. A map of reduced von Mises stresses was used to search for potential fatigue crack areas. The research [loading] was conducted on two mutually perpendicular planes positioned in such a way that the edge intersecting the planes coincided with the axis of the system. The research indicated that the connecting screw showed the least sensitivity (stress change) to the change in the loading plane, while the value of preload has a significant impact on the achieved fatigue strength of the system. In contrast, the endosteal implant (root) and the prosthetic connector showed the greatest sensitivity to the change in the loading plane. The method of mounting [securing] the endosteal implant using a holder, despite meeting the standards, may contribute to generating excessive stress concentration in the threaded part. Observation of the prosthetic connector in the Optima 3.35 system, cyclically loaded with a force of F ≈ 300 N in the area of the upper hexagonal peg, revealed a fatigue fracture. The observed change in stress peak in the dental connector for two different force application surfaces shows that the positioning of the dental system (setting of the socket in relation to the force action plane) is significantly decisive in estimating the limited fatigue strength.

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Glucose metabolism is a crucial biological pathway maintaining the activation of extra- and intracellular signaling pathways involved in the immune response. Immune cell stimulation via various environmental factors results in their activation and metabolic reprogramming to aerobic glycolysis. Different immune cells exhibit cell-type-specific metabolic patterns when performing their biological functions. Numerous published studies have shed more light on the importance of metabolic reprogramming in the immune system. Moreover, this knowledge is crucial for revealing new ways to target inflammatory pathologic states, such as autoimmunity and hyperinflammation. Here, we discuss the role of glycolysis in immune cell activity in physiological and pathological conditions, and the potential use of inhibitors of glycolysis for disease treatment.

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(1) Background: Mandibular fractures are common, with the condylar process being a frequent site of injury, accounting for 25-45% of cases. This research aims to assess the mechanical suitability of various plates for high-neck condyle fractures. (2) Methods: Polyurethane models mimicking high-neck condyle fractures were utilized in this study. Sixteen distinct plate designs, constructed from titanium sheets, were tested. The figures underwent force assessments on a durability testing apparatus, and the relationship between used force and fracture movement was documented. (3) Results: For high-neck breaking, the two straight plates emerged as the most effective, aligning with established osteosynthesis standards. The second-best plate exhibited nearly half the strength of the gold standard. (4) Conclusions: In response to the aim of this study, considering the mechanical aspects, the double plain plate stands out as the optimal choice for osteosynthesis in cases of high-neck fractures of the mandibular condylar process. In addition, the authors propose the Mechanical Excellence Factor (MEF) as a superior metric for appraising a plate's mechanical force, surpassing the conventional Plate Design Factor (PDF).

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The increased demand for implants that do not pose a threat to patients diagnosed using high-resolution magnetic resonance imaging and concerns arising from titanium allergies require the development of alternative implant materials. One promising concept is a use of zirconium as corrosion-resistant, nontoxic material that is lower in magnetic susceptibility. To achieve this, safe and efficient surface treatment methods of zirconium metal have to be developed. In this study, zirconium samples were treated with fluoride-free and fluoride-containing etching mixtures to determine their effect on the surface of Zr. SEM images were taken to investigate the preliminary effects of the etchants. Then, a second set of experiments was carried out using mixtures of HF-H2SO4 and ammonium persulfate-fluoride salts, as they gave the most promising results in the first trial. SEM images were taken and measurements on roughness, wettability, and atomic composition were made. The results showed an even zirconium surface in APS-fluoride salts, along with the formation of pits (1-3 µm) similar to those found in commercially available implants. There was no significant increase in the roughness of the treated samples. The addition of NO3- ions in the form of KNO3 speeded up etching and promoted pit formation. The HF-H2SO4 mixture was found to give unsatisfying results, as the surface was too rough and the formed pits were too large. It was concluded that etching zirconium in ammonium persulfate and fluoride salts is a promising area of research for the preparation of zirconium implants; however, further research has to be carried out on sandblasted samples.

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The MaI Implants® method offers a modern treatment option for specific patients who lack sufficient bone for traditional screw-based implants. The aim of the article is to use Finite Element Analysis (FEA) to examine the behavior of a subperiosteal implant under actual conditions within the oral cavity and to assess the impact of various mechanical factors on the durability of the MaI Implants®. A strength analysis was conducted using Finite Element Analysis for two models. The first was a single subperiosteal implant, while the second was a model of an arch consisting of two single subperiosteal implants connected by a bar. Based on the obtained results, it can be observed that the increase in load from 100 N to 800 N leads to an increase in displacements throughout the implant. Changing the angle from 90 to 30 degrees resulted in a 576% increase in the average displacement value across all multi-units. Stresses in the multi-units range from 23.7 MPa to 268.5 MPa. The lack of proper stabilization of the implant has the greatest impact on the results of displacements. Such displacements are significant for the later positioning of the implant compared to the initial conditions.

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(1) Background: The mandible is the most frequently injured component of the facial skeleton, with 25-45% of mandibular fractures involving the condylar process. This study aims to mechanically compare which plates are most suitable for use in low-neck fractures of the condyle. (2) Methods: Polyurethane mandibular models with simulated low-neck fractures were tested using 37 distinct plate designs. These plates were fabricated from 1 mm thick, grade 23 titanium sheets. The models were then subjected to force tests on a strength machine, and the correlation between applied force and fracture displacement was recorded. (3) Results: For low-neck fractures, XCP side-dedicated 3+5 and ACP-T plates demonstrated strength comparable to that of two straight plates, the current gold standard in osteosynthesis. (4) Conclusions: The Mechanical Excellence Factor (MEF) introduced by the authors provides a more accurate metric for theoretically predicting a plate's mechanical strength compared to the Plate Design Factor (PDF). Eight plate characteristics were utilized to calculate the MEF. Employing the MEF allows for rapid, preliminary validation before undertaking strength tests. Furthermore, the findings of this study can guide the selection of the most durable plate designs for subsequent fatigue testing.

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BACKGROUND: Presently, the management of patients with maxilla bone defects of the Cawood V or VI class is achieved using zygomatic or individual implants or through augmentation of the bone. For zygomatic implants, the ORIS criteria represent the most common factor in helping practitioners register success rates. The zygomatic anatomy-guided approach (ZAGA)and zygomatic orbital floor (ZOF) are factors that are crucial to examining the anatomy of a particular patient before the procedure. The aim of thisarticle is to find the statistical relationship between the abovementioned terms and other factors. METHODS: A total of 81 patients underwent zygomatic implant procedures in different configurations. The ORIS, ZAGA, and ZOF parameters were compared with other factors such as type of surgery, sex, age, and the anatomy of the zygomatic bone. RESULTS: Most patients in this article were classified as ZAGA Class 2. The relationships between type of surgery and ZAGA classification, and ZAGA and sinus/maxilla zygomatic implant localization were statistically significant. CONCLUSIONS: The ZAGA and ZOF scales are practical and valuable factors that should be taken into account before surgery, whereas to date, criteria better than the ORIS scale have not been described in terms of the success of zygomatic implants. The ZOF scale might omit perforation of the orbit because this parameter warns a practitioner to be aware of the anatomy of the orbit.

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BACKGROUND: The mandible is the most injured part of the facial skeleton, and 25-40% of mandibular fractures involve the condyle process. The aim of this study is to answer the question of the relationship between screw pullout and/or plate fracture during osteosynthesis. METHODS: We tested polyurethane models of mandibles whose condylar process was cut (simulating a fracture) and fused using plates and screws. RESULTS: A total of 672 plates were tested. A total of 25.6% of them were fractured during the test, with most being fractures of the base of the condyle. More screws (81.97%) are pulled out from the ramus than from the condyle-69.15%. CONCLUSIONS: The gold standard in the osteosynthesis of condylar fractures is two straight plates. Other than these, there is no one-size-fits-all plate for every type of fracture. Plates fixed with fewer screws (smaller plates used in higher-lying fractures) are more likely to result in screw pullout. On the other hand, in plates fixed with more screws, plate fracture is more common.

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In the surgical treatment of the most common fracture of the mandible, which is a fracture of the condylar base, a great choice of different plate shapes is observed. The aim of this study was to determine which shape gives the greatest fixation stiffness. To ensure homogeneity in comparison, tests were performed on polyurethane models divided at the level of the condylar base fracture and each were fixed with 51 plates. The plates were cut from a 1 mm thick grade 23 titanium sheet. The models were then loaded and the force required for 1 mm of fracture displacement was recorded. It was noted that in addition to osteosynthesis from two simple plates, there were also two dedicated single plates with similar rigidity. Among the large number of described designs of plates, there is considerable variation in terms of the stability of the fixation performed with them. The proposed Mechanical Excellence Factor allows a pre-evaluation of the expected rigidity of fixation with a given plate shape without the need for a loading experiment. The authors expect this to be helpful for surgeons in the application of relevant plates, as well for inventors of new plates for the osteosynthesis of basal fractures in mandibular condyle.

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2-Deoxy-d-glucose (2-DG), a compound known to interfere with d-glucose and d-mannose metabolism, has been tested as a potential anticancer and antiviral agent. Preclinical and clinical studies focused on 2-DG have highlighted several limitations related to 2-DG drug-like properties, such as poor pharmacokinetic properties. To overcome this problem, we proposed design and synthesis of novel 2-DG prodrugs that subsequently could be tested using a variety of biochemical and molecular methods. We narrowed here our focus to esters of 2-DG as potential prodrugs based on the hypothesis that ubiquitous esterases will regenerate 2-DG, leading to increased circulation time of drug and adequate organ and tumor penetration. Testing this hypothesis in vitro and, especially, in vivo requires significant amounts of respective pure mono- and previously unknown di-acetylated water-soluble derivatives of 2-DG. Development of their efficient and practical method of synthesis was imperative. We describe novel facile and scalable syntheses of seven selectively acetylated water-soluble derivatives of 2-DG and present a detailed 1H and 13C NMR analysis of all final products. X-ray diffraction analysis has been performed for compound WP1122 that was selected for detailed preclinical and subsequent clinical evaluation as potential anticancer or antiviral agent.

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The long-term monitoring of a fetus with genetic and non-genetic anomalies is still a challenge for prenatal medicine. Ultrasound screening must be based on some measurement ranges, which show the trend of development of fetal body parts in a given period of time. One of them is the fetal ear auricle. This study presents an analysis of the fetal ear auricle length in healthy fetuses to establish normal ranges of fetal ear auricle length. The study group included 132 healthy fetuses. The gestational age of healthy fetuses ranged from 17.0 to 39.5 weeks of gestation according to LMP. The range of fetal ear length measurement was 10.00-40.00 mm with an average value of 23.49 mm. In the group of fetuses in the second trimester of pregnancy, the range of fetal ear length measurement was 18.00-28.00 mm, whereas in the group of fetuses in the third trimester of pregnancy, the range was 16.00-40.00 mm. In order to check the usefulness of this parameter, an analysis of this marker in fetuses with extracardiac anomalies, including genetic and non-genetic disorders is shown. The fetal ear measurement can fall within the normal range even if there are some genetic or non-genetic disorders. Therefore, the fetal ear measurement does not provide any diagnostic value in terms of detecting any fetal genetic and non-genetic disorders, which is supported by the analysis of the data provided in this study. Our study has proved that measurement of the fetal ear auricle is possible; however, its clinical usefulness for perinatal management is currently very limited.

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Anthracyclines have contributed significantly to remarkable improvements in overall survival and are regarded as the most effective cytostatic drug for cancer treatment in various malignancies. However, anthracyclines are a significant cause of acute and chronic cardiotoxicity in cancer patients, and long-term cardiotoxicity can lead to death in about one-third of patients. Several molecular pathways have been implicated in the development of anthracycline-induced cardiotoxicity, although the underlying mechanisms of some molecular pathways are not fully elucidated. It is now generally believed that anthracycline-induced reactive oxygen species (resulting from intracellular metabolism of anthracyclines) and drug-induced inhibition of topoisomerase II beta are the key mechanisms responsible for the cardiotoxicity. To prevent cardiotoxicity, several strategies are being followed: (i) angiotensin-converting enzyme inhibitors, sartans, beta-blockers, aldosterone antagonists, and statins; (ii) iron chelators; and (iii) by development of new anthracycline derivatives with little or no cardiotoxicity. This review will discuss clinically evaluated doxorubicin analogues that were developed as potentially non-cardiotoxic anticancer agents and include recent development of a novel liposomal anthracycline (L-Annamycin) for the treatment of soft-tissue sarcoma metastatic to the lung and acute myelogenous leukaemia.

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Approximately 1.5 billion chronic liver disease (CLD) cases have been estimated worldwide, encompassing a wide range of liver damage severities. Moreover, liver disease causes approximately 1.75 million deaths per year. CLD is typically characterized by the silent and progressive deterioration of liver parenchyma due to an incessant inflammatory process, cell death, over deposition of extracellular matrix proteins, and dysregulated regeneration. Overall, these processes impair the correct function of this vital organ. Cirrhosis and liver cancer are the main complications of CLD, which accounts for 3.5% of all deaths worldwide. Liver transplantation is the optimal therapeutic option for advanced liver damage. The liver is one of the most common organs transplanted; however, only 10% of liver transplants are successful. In this context, regenerative medicine has made significant progress in the design of biomaterials, such as collagen matrix scaffolds, to address the limitations of organ transplantation (e.g., low donation rates and biocompatibility). Thus, it remains crucial to continue with experimental and clinical studies to validate the use of collagen matrix scaffolds in liver disease.

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Tissue endothelial cells express ABC-transporter enzymes that change the concentration of small molecules within different tissue compartments. These "blood-tissue barriers" have been shown to directly affect the efficacy and toxicity of anticancer, antimicrobial, psychiatric, and anti-epileptic drugs. Currently this phenomenon is best studied for the blood-brain barrier, but remains enigmatic for most other tissues. In addition, canonical pharmacokinetic theory specifically assumes an equal concentration of free drug within all tissue compartments. Inspired by Lipinski's "rule of 5," we here clarify current knowledge on drug-tissue distribution by: 1) curating the in-vivo literature on 73 drugs across 23 tissues and 2) developing two graphical web-based applications to visually describe and interpret data. These curated in-vivo dataset and visualization tools enabled us to achieve new insights into the logic of the barrier-tissue organization and showed remarkable correspondence to whole-body imaging of radiolabeled molecules.

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ABSTRACT: Antibody-drug conjugates (ADCs) are designed to deliver cytotoxic payloads to distinctive target-expressing cancer cells. Following internalization, the ADCs are routed to different compartments in the cells, where cleavage of the linker causes release of the cytotoxic cargo. With such a delivery system, more effective payloads can reach cancer cells, allowing for more efficient treatment and dosing schedule. The monoclonal antibody (mAb) component of ADC plays a crucial role in the effective targeting of cancer cell-specific antigens while minimizing binding to normal cells. Often, the same mAbs used in ADCs can be labeled instead with radionuclides suitable for positron emission tomography or gamma-camera scintigraphy. To achieve high sensitivity and specificity for imaging, radiolabeled mAbs must have high affinity for the antigen, favorable pharmacokinetic properties, and a low toxicity profile. The use of radiolabeled mAbs permits the noninvasive interrogation of specific target expression on tumor cells and assessment of tumor heterogeneity in vivo by a simple diagnostic imaging scan that may include the whole body in the field of view. With this approach, radiolabeled mAbs can serve as important imaging biomarkers to predict the optimal delivery of ADCs to tumors and be used to monitor therapy with follow-up scans. Moreover, the same mAb can then be radiolabeled with an analogous radionuclide for the delivery of ß-emitters, α-particles, or Auger electrons as part of a radioimmunotherapy approach. The purpose of this review is to introduce key concepts regarding radiolabeled mAbs targeting various tumor antigens (CD20, CDH3, type I insulinlike growth factor receptor, prostate-specific membrane antigen, and human epidermal growth factor receptor 2) that are being used in the clinical setting or undergoing development.

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Viral infection almost invariably causes metabolic changes in the infected cell and several types of host cells that respond to the infection. Among metabolic changes, the most prominent is the upregulated glycolysis process as the main pathway of glucose utilization. Glycolysis activation is a common mechanism of cell adaptation to several viral infections, including noroviruses, rhinoviruses, influenza virus, Zika virus, cytomegalovirus, coronaviruses and others. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Glycolysis inhibitors, especially 2-deoxy-D-glucose (2-DG), have been intensively studied as antiviral agents. However, 2-DG's poor pharmacokinetic properties limit its wide clinical application. Herein, we discuss the potential of 2-DG and its novel analogs as potent promising antiviral drugs with special emphasis on targeted intracellular processes.

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