The Impact of Glycolysis and Its Inhibitors on the Immune Response to Inflammation and Autoimmunity.

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.

Development of a Novel Tool To Demystify Drug Distribution at Tissue-Blood Barriers.

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.

The Antiviral Effects of 2-Deoxy-D-glucose (2-DG), a Dual D-Glucose and D-Mannose Mimetic, against SARS-CoV-2 and Other Highly Pathogenic Viruses.

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.

Experimental and Computational Studies on Structure and Energetic Properties of Halogen Derivatives of 2-Deoxy-D-Glucose.

The results of structural studies on a series of halogen-substituted derivatives of 2-deoxy-D-glucose (2-DG) are reported. 2-DG is an inhibitor of glycolysis, a metabolic pathway crucial for cancer cell proliferation and viral replication in host cells, and interferes with D-glucose and D-mannose metabolism. Thus, 2-DG and its derivatives are considered as potential anticancer and antiviral drugs. X-ray crystallography shows that a halogen atom present at the C2 position in the pyranose ring does not significantly affect its conformation. However, it has a noticeable effect on the crystal structure. Fluorine derivatives exist as a dense 3D framework isostructural with the parent compound, while Cl- and I-derivatives form layered structures. Analysis of the Hirshfeld surface shows formation of hydrogen bonds involving the halogen, yet no indication for the existence of halogen bonds. Density functional theory (DFT) periodic calculations of cohesive and interaction energies (at the B3LYP level of theory) have supported these findings. NMR studies in the solution show that most of the compounds do not display significant differences in their anomeric equilibria, and that pyranose ring puckering is similar to the crystalline state. For 2-deoxy-2-fluoro-D-glucose (2-FG), electrostatic interaction energies between the ligand and protein for several existing structures of pyranose 2-oxidase were also computed. These interactions mostly involve acidic residues of the protein; single amino-acid substitutions have only a minor impact on binding. These studies provide a better understanding of the structural chemistry of halogen-substituted carbohydrates as well as their intermolecular interactions with proteins determining their distinct biological activity.

Hyperpolarized Pyruvate MR Spectroscopy Depicts Glycolytic Inhibition in a Mouse Model of Glioma.

BackgroundA generation of therapies targeting tumor metabolism is becoming available for treating glioma. Hyperpolarized MRI is uniquely suited to directly measure the metabolic effects of these emerging treatments.PurposeTo explore the feasibility of the use of hyperpolarized [1-carbon 13 {13C}]-pyruvate for real-time measurement of metabolism and response to treatment with a glycolytic inhibitor in an orthotopic mouse model of glioma.Materials and MethodsIn this animal study, anatomic MRI and dynamic 13C MR spectroscopy were performed at 7 T during intravenous injection of hyperpolarized [1-13C]-pyruvate on mice with orthotopic U87MG glioma and healthy control mice. Anatomic MRI and dynamic 13C MR spectroscopy were repeated after administration of the glycolytic inhibitor WP1122, a prodrug of 2-deoxy-d-glucose. All experiments were conducted in athymic nude mice between October 2016 and March 2017. Hyperpolarized lactate production was quantified as an apparent reaction rate, or kPL, and normalized lactate ratio (nLac). The Wilcoxon signed-rank test was used to assess changes in paired measures of lactate production before and after treatment.ResultsThirteen 12-16-week-old female mice and five healthy female mice underwent anatomic MRI and hyperpolarized [1-13C]-pyruvate spectroscopy. Large contrast agent-enhanced tumors were shown in mice with glioma at T2-weighted and T1-weighted postcontrast MRI by postimplantation day 40. After treatment with WP1122, a decrease in lactate was observed in mice with glioma (baseline and treatment mean kPL, 0.027 and 0.018 sec-1, respectively, P = .01; baseline and posttreatment mean nLac, 0.28 and 0.22, respectively, P = .01) whereas no significant decrease was observed in healthy control mice (baseline and posttreatment mean kPL, 0.011 and 0.017 sec-1, respectively, P = .91; baseline and posttreatment mean nLac, 0.16 and 0.21, respectively, P = .84).ConclusionHyperpolarized carbon 13 measurements of pyruvate metabolism can provide rapid feedback for monitoring treatment response in glioma.© RSNA, 2019.

Assessment of nasal and oral flow of amniotic fluid in 46 non-anomalous fetuses with sonographic and echocardiographic examination.

OBJECTIVES: The aim of the paper was to assess nasal and oral amniotic fluid flows, with the use of color ultrasound and spectral Doppler, in normal fetuses. MATERIAL AND METHODS: Forty-six fetuses of singleton gestations were studied prospectively. Spectrum imaging and maximal nasal fluid flow velocities were described. Episodes of regurgitation (external flow from the mouth), swallowing (internal flow at the level of oropharynx and then entrance to the esophagus) were evaluated in two groups: Fetuses < 27 weeks of gestation and 27 weeks of gestation and older. Statistical analysis was done using Fischer exact test and t-test at p = 0.05. RESULTS: Twenty-one fetuses were < 27 weeks of gestational age and presented mean maximal both inspiratory and expiratory nasal fluid flow velocities significantly lower than twenty-five fetuses who were ≥ 27 weeks of gestational age (p = 0.035 and p = 0.031 respectively, t-test). Episodes of regurgitation were observed more frequently in group of "younger" fetuses (p = 0.006, Fischer exact test). There was no statistically significant relationship between irregular nasal flow spectrum by color Doppler and gestational age group (p = 0.264, Fischer exact test). CONCLUSIONS: Episodes of regurgitation occurred in normal fetuses < 27th week of gestation. Fast amniotic nasal fluid flows without episodes of regurgitation were observed more frequently in fetuses ≥ 27 weeks and it could be interpreted as an additional sonographic feature of prenatal maturation.

Bis-anthracycline WP760 abrogates melanoma cell growth by transcription inhibition, p53 activation and IGF1R downregulation.

Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to DNA intercalation, interference with topoisomerase activity, and induction of double-stranded DNA breaks. Since modification of anthracyclines can profoundly affect their pharmacological properties we attempted to elucidate the mechanism of action, and identify possible molecular targets, of bis-anthracycline WP760 which previously demonstrated anti-melanoma activity at low nanomolar concentrations. We studied the effect of WP760 on several human melanoma cell lines derived from tumors in various development stages and having different genetic backgrounds. WP760 inhibited cell proliferation (IC50 = 1-99 nM), impaired clonogenic cell survival (100 nM), and inhibited spheroid growth (≥300 nM). WP760 did not induce double-stranded DNA breaks but strongly inhibited global transcription. Moreover, WP760 caused nucleolar stress and led to activation of the p53 pathway. PCR array analysis showed that WP760 suppressed transcription of ten genes (ABCC1, MTOR, IGF1R, EGFR, GRB2, PRKCA, PRKCE, HDAC4, TXNRD1, AKT1) associated with, inter alia, cytoprotective mechanisms initiated in cancer cells during chemotherapy. Furthermore, WP760 downregulated IGF1R and upregulated PLK2 expression in most of the tested melanoma cell lines. These results suggest that WP760 exerts anti-melanoma activity by targeting global transcription and activation of the p53 pathway and could become suitable as an effective therapeutic agent.

A case of intraparotid schwannoma in a juvenile: Clinical, pathological, ultrastructural, and immunohistopathological study, including an examination of Ki-67 and MCM-3 expressions.

Pleomorphic adenoma, the most common benign nonvascular tumor of the parotid gland in juveniles, should be differentiated from other extremely rare tumors, including schwannoma. In this article, we present a rare case of an intraparotid schwannoma in a juvenile, along with the patient history, a description of pathological features, and the results of ultrastructural and immunohistochemical examination. The respective labeling indexes of Ki-67 and MCM-3, i.e., the mean proportions of positive tumor cells out of 1000 tumoral cells counted in 10 microscopic fields at ×400 magnification, given as a percentage, were found to be 0.82% and 0.4%, respectively.

Comparison between immunohistochemical expression of Ki-67 and MCM-3 in major salivary gland epithelial tumors in children and adolescents. Preliminary study.

While Ki-67 expression is frequently used as an indicator of tumor cell proliferation, alternative markers have also been proposed. Possible alternative indicators of proliferation are the minichromosome maintenance (MCM) proteins, whose levels are inversely associated with tumor cell differentiation. The aim of this preliminary study was to compare the levels of Ki-67 and MCM-3 expression in major salivary gland epithelial tumors in all children and adolescents who underwent surgery in our department in the years 2009-2014. The histopathological diagnosis of the subjects was reviewed, as well as the expression of Ki-67 and MCM-3 in post-op specimens of the tumors. The normality of data was checked with the Shapiro-Wilk test. The t test for independent variables or the U test was used as appropriate to determine statistically significant differences in the expression of Ki-67 and MCM-3. Five cases of pleomorphic adenoma, one of myoepithelioma, one of basal cell adenoma and one of mucoepidermoid carcinoma were identified. Significantly greater MCM-3 than Ki-67 expression was observed in every case. The results of our preliminary study emphasize the need for future research on MCM-3 as a sensitive proliferation marker, providing an alternative to Ki-67, in cases of various major salivary gland epithelial tumors in children and adolescents.

Cardiovascular profile score in 44 fetuses with cervicofacial tumors.

BACKGROUND: Cervicofacial tumors are rarely detected by prenatal ultrasound, and prenatal counseling is very difficult as not much information is available about this problem in the literature, other than cases reports. OBJECTIVES: The aim of this study was to know if fetal echocardiography examination is helpful in those cases. MATERIAL AND METHODS: Forty-four fetuses with cervicofacial tumors detected in utero by ultrasonography and referred to our unit were assessed and the cardiovascular profile score (CVPS) based on echocardiography examinations was calculated. The data were analyzed by the standard statistical tests and Pearson's χ2-test (significance level P=0.05). RESULTS: CVPS<8 was diagnosed in 10 fetuses (23%). Structural or functional cardiovascular anomalies were present in 17 fetuses (39%). The statistically significant correlation between the CVPS<8 and the poor outcome was confirmed (P<0.05). CONCLUSION: We recommend fetal echocardiography and CVPS evaluation before counseling in fetuses with cervicofacial tumors as cardiovascular dysfunction diagnosed prenatally may seriously affect survival of the fetus as well as prenatal counseling and need for cardiac treatment.

Active targeting using HER-2-affibody-conjugated nanoparticles enabled sensitive and specific imaging of orthotopic HER-2 positive ovarian tumors.

Despite advances in cancer diagnosis and treatment, ovarian cancer remains one of the most fatal cancer types. The development of targeted nanoparticle imaging probes and therapeutics offers promising approaches for early detection and effective treatment of ovarian cancer. In this study, HER-2 targeted magnetic iron oxide nanoparticles (IONPs) are developed by conjugating a high affinity and small size HER-2 affibody that is labeled with a unique near infrared dye (NIR-830) to the nanoparticles. Using a clinically relevant orthotopic human ovarian tumor xenograft model, it is shown that HER-2 targeted IONPs are selectively delivered into both primary and disseminated ovarian tumors, enabling non-invasive optical and MR imaging of the tumors as small as 1 mm in the peritoneal cavity. It is determined that HER-2 targeted delivery of the IONPs is essential for specific and sensitive imaging of the HER-2 positive tumor since we are unable to detect the imaging signal in the tumors following systemic delivery of non-targeted IONPs into the mice bearing HER-2 positive SKOV3 tumors. Furthermore, imaging signals and the IONPs are not detected in HER-2 low expressing OVCAR3 tumors after systemic delivery of HER-2 targeted-IONPs. Since HER-2 is expressed in a high percentage of ovarian cancers, the HER-2 targeted dual imaging modality IONPs have potential for the development of novel targeted imaging and therapeutic nanoparticles for ovarian cancer detection, targeted drug delivery, and image-guided therapy and surgery.

AD-O53.2--a novel recombinant fusion protein combining the activities of TRAIL/Apo2L and Smac/Diablo, overcomes resistance of human cancer cells to TRAIL/Apo2L.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors became promising molecules for selective targeting of tumor cells without affecting normal tissue. Unfortunately, cancer cells have developed a number of mechanisms that confer resistance to TRAIL\Apo2L-induced apoptosis, which substantiates the need for development of alternative therapeutic strategies. Here we present a recombinant variant of TRAIL\Apo2L peptide, named AD-O53.2, fused to the peptide-derived from Smac/Diablo protein-the natural inhibitor of the apoptotic X-linked IAP (XIAP) protein considered as a pro-apoptotic agent. The proposed mechanism of action for this construct involves specific targeting of the tumor by TRAIL\Apo2L followed by activation and internalization of pro-apoptotic peptide into the cancer cells. While in the cytoplasm , the Smac\Diablo peptide inhibits activity of X-linked IAP (XIAP) proteins and promotes caspase-mediated apoptosis. AD-O53.2 construct was expressed in E.coli and purified by Ion Exchange Chromatography (IEC). Derived protein was initially characterized by circular dichroism spectroscopy (CD), HPLC-SEC chromatography, surface plasmon resonance, protease activation and cell proliferation assays. Our Smac/Diablo-TRAIL fusion variant was tested against a panel of cancer cells (including lung, colorectal, pancreatic, liver, kidney and uterine) and showed a potent cytotoxic effect with the IC50 values in femtomolar range for the most sensitive cell lines, while it remained ineffective against non-transformed HUVEC cells as well as isolated normal human and rat hepatocytes. Importantly, the construct was well tolerated by animals and significantly reduced the rate of the tumor growth in colon and lung adenocarcinoma animal models.

Electrochemical Polishing of Ti and Ti6Al4V Alloy in Non-Aqueous Solution of Sulfuric Acid.

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.

New Radiological Corticalization Index as an Indicator of Implant Success Rate Depending on Prosthetic Restoration-5 Years of Follow-Up.

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.

Optimal Plate Choice for High-Neck Mandibular Condyle Fracture: A Mechanistic Analysis of 16 Options.

(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).

Finite Element Analysis and Fatigue Test of INTEGRA Dental Implant System.

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.

Targeting branched N-glycans and fucosylation sensitizes ovarian tumors to immune checkpoint blockade.

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.

[Craniofacial malformations in prenatal ultrasound evaluation. Literature review]. / Malformacje twarzoczaszki w prenatalnej ocenie ultrasonograficznej. Przeglad pismiennictwa.

Fetal face is the key anatomical location, both psychologically and clinically for the mother and the clinician. Ultrasound prenatal examination of the maxillofacial region allows to evaluate the fetal face in the first weeks of gestation. In ambulatory intravaginal ultrasound, sensitivity of the facial defect detection is 20-30% in cases without the risk of TORCH and fetal abnormalities, which may arouse suspicion of the presence of facial malformation. Facial defects form a wide group of pathologies. Unfortunately challenges connected with 2D and 3D ultrasound imaging cause frequent misdiagnoses in early gestation. Maxillofacial abnormalities can be solitary or they can coexist with other abnormalities or syndromes. In case of detecting a facial defect, a precise and thorough ultrasound of whole fetal body is necessary whereas in case of detecting any fetal body abnormality a precise and thorough ultrasound examination of the fetal face is obligatory Unfortunately most contemporary prenatal ultrasound standards propose only the overall "face and orbits" evaluation of the fetal face. The evaluation is difficult at 23 and 24 weeks of gestation and seems to be rather challenging in the third trimester of gestation. Not only facial malformations but also facial dimorphic features may lead to the suspicion of genetic syndrome and they may be extremely important in making correct diagnosis. Attempts at standardization in fetal face ultrasound evaluation have proved to be extremely difficult. Advantages of 2D ultrasound over 3D ultrasound and 3D ultrasound over 2D ultrasound in fetal face evaluation have been a topic of much debate. Most typically fetal face is examined with 2D ultrasound in a few basic planes: coronary sagittal, frontal and oblique. The planes preferred in the evaluation of facial structures are discussed in details in the paper Fetal facial defects evaluated in the ultrasound examination may be divided into a few main groups: examination of the orbit and eyeball defects, examination of the external nose and nasal cavity defects, examination of the cleft defects involving the lip, hard and soft palate which may be unilateral or bilateral, examination of external ear defects, examination of mandibular defects and detection of fetal tumors. 3D ultrasound evaluation of the fetal face is extremely useful in visualization of the face, thus presenting a problem to parents and clinicians. Prenatal ultrasound examination provides necessary and extremely useful data concerning fetal facial abnormalities, which allows to plan care and further treatment including interventions in pediatric ENT, pediatric surgery and plastic surgery areas. Cooperation of ultrasound diagnostician and clinicians taking care of a child in the future is therefore necessary when designing treatment scheme in cases of fetal facial defects.

Measurement of the Fetal Ear Length Has No Clinical Value.

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.

Zirconium Surface Treatment via Chemical Etching.

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.