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In a patient with congenitally corrected transposition of the great arteries, dilatation of the atrioventricular valve annulus related to worsening of systemic ventricular function, which worsened systemic atrioventricular valve (SAVV) functional regurgitation. In this article, we report a case of successful transcatheter treatment with MitraClip (Abbott Vascular, Santa Clara, CA, USA) in a 68-year-old female patient with congenitally corrected transposition of the great arteries and severe SAVV failure using imaging modalities. The patient had been hospitalized four times within 8 months, receiving optimal medical therapy for severe SAVV regurgitation and systemic ventricular failure. In this patient, the risk associated with surgery was considered extremely high owing to severe heart failure and liver cirrhosis. We positioned two clips appropriately, side by side, in between the anterior and septal leaflets, guided by computed tomography and three-dimensional echocardiography. The procedure resulted in optimal post-procedural reduction of regurgitation without stenosis, with a good clinical outcome noted at 2-year follow-up. LEARNING OBJECTIVE: Since surgery for adult congenital heart disease is linked to high risk, we seek less invasive treatment for such patients. In patients with congenital heart disease and severe valve regurgitation, the use of MitraClip (Abbott Vascular, Santa Clara, CA, USA) could be a feasible option for select cases.

Objective To clarify the relationship between oral lichen planus (OLP) and systemic oxidative stress, we examined serum antioxidant and urinary oxidative stress marker levels in patients with OLP. Methods Fifteen female patients with clinical and histopathological diagnoses of OLP were enrolled in this study. The mean patient age was 67.6 years (range, 56–81 years). Ten age- and sex-matched volunteers without oral mucosal lesions were selected as a control group. Serum levels of the antioxidants vitamin A, vitamin C, vitamin E, folate, zinc, uric acid, and superoxide dismutase activity were evaluated. Urinary levels of the oxidative stress marker 8-hydroxy2’-deoxyguanosine (8-OHdG) were measured by enzyme immunoassays. All values were compared between the two groups. Results The mean value of serum vitamin C was lower in the OLP group (5.73 ± 2.34μg/mL) than in the control group (9.22 ± 3.65 μg/mL; P = 0.0125). Serum levels of vitamin A, vitamin E, folate, zinc, uric acid, and superoxide dismutase activity did not significantly differ between the two groups. The mean values of creatinine adjusted urinary 8-OHdG were 10.1 ± 7.34 ng/mg creatinine in the OLP group and 13.7 ± 12.7 ng/mg creatinine in the control group; these values did not significantly differ between the two groups (P = 0.5189). Conclusion Our results suggested that serum levels of vitamin C are low in patients with OLP. However, oxidative stress (determined by measurement of urinary 8-OHdG level) was not significantly higher in patients with OLP. Thus, the relationship between OLP and systemic oxidative stress was not fully elucidated in this study.

Background The efficacy assessment of human anti-IgE monoclonal antibodies (mAbs) in animal models before clinical trials is hampered due to the lack of cross-reactivity of anti-IgE mAbs between species. Objective We developed CRE-DR (an anti-dog IgE monoclonal antibody), an anti-IgE mouse mAb that recognizes canine and human IgE, and then examined its IgE specificity and cross-reactivity between three animal and human species. Methods After mouse immunization with a synthetic peptide derived from canine IgE (282 NTNDWIEGETYYC294 ), we generated a hybridoma producing CRE-DR. The CRE-DR purified from the ascites of hybridoma-inoculated mice was used for ELISA and Western blot analysis to examine reactivity to dog, human, and rodent IgEs as well as recombinant bovine serum albumin (BSA)-conjugated to canine, human, and rodent IgE amino acid peptides corresponding to the immunizing sequence. We then performed enzyme-linked immunosorbent assays (ELISAs) for dog IgE using sera from dogs with atopic dermatitis (AD) after inhibition with canine IgE and IgG. The amino acid sequence recognized by CRE-DR was identified by ELISA using synthetic peptides. Results CRE-DR is a monoclonal mouse IgG1κ specific for dog IgE, and the ELISA values in atopic dog sera were inhibited by dog IgE, but not dog IgG. The binding of CRE-DR to human IgE was relatively maintained, but not to rodent IgEs, which results were confirmed with the BSA-conjugated IgE peptides of the various species. The CRE-DR reactivity was supported by the comparison of amino acid sequence of CRE-DR epitope, DWIEGETYYC, in dog IgE; one, two, and three amino acids were substituted in the human, rat, and mouse IgE epitopes, respectively. Conclusions and clinical relevance CRE-DR is a mAb cross-reactive to dog and human IgEs, which can allow the use of a dog model of allergy to test the efficacy of a CRE-DR-derived anti-IgE therapeutic mAb before human clinical trials.

Rapid ventricular pacing (RVP) is commonly employed during transcatheter aortic valve replacement (TAVR); however, frequent TAVR is associated with worse prognoses. The retrograde INOUE-BALLOON® (IB) allows balloon aortic valvuloplasty (BAV) without RVP. The aim of this study was to evaluate the feasibility of retrograde IB for TAVR preparation. The study population included 178 consecutive patients (mean age, 84 ± 5 years; male, 47%) who underwent retrograde BAV before prosthetic valve replacement via the transfemoral approach. Patients were divided into a retrograde IB group without RVP (n = 74) and a conventional balloon (CB) group with RVP (n = 104). The primary endpoint was prolonged hypotension after BAV (reduced systolic pressure p = 0.011). Balloons were able to penetrate and expand the aortic valve in both groups. RVP was used less for total TAVR in the IB group compared with the CB group. The aortic valve area-index after BAV was not significantly different between the two groups (0.72 ± 0.14 cm2/m2 vs. 0.71 ± 0.12 cm2/m2; p = 0.856). Multivariate analysis demonstrated that IB use was associated with avoidance of prolonged hypotension (OR, 0.27 [0.059–0.952]; p = 0.041). In conclusion, BAV using retrograde IB without RVP is both safe and feasible. More stable hemodynamics were achieved using retrograde IB by avoiding RVP during TAVR.

Objective In Japan, immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), and cyclosporine A (CsA) is the standard of care in patients with aplastic anemia (AA) who are not indicated for stem-cell transplantation, although some patients may experience relapse. This study assessed the efficacy and safety of eltrombopag in combination with rabbit-ATG/CsA in IST-naive patients with non-severe or severe AA in Japan. Methods In this non-randomized, open-label, single-arm, phase II study, rabbit-ATG/CsA and eltrombopag were initiated on Days 1 and 15 (±3 days), respectively, and continued for ≥26 weeks; rabbit-ATG was given for 5 days (Days 1 to 5). The primary endpoint was the overall response rate (ORR) at Week 26. Patients Patients with AA who were IST-naive and ≤70 years old or between 71 and 75 years old based on the recommendation of the investigator were enrolled in Japan. Results Of the 11 enrolled patients, 10 started treatment with eltrombopag. The ORRs at Weeks 26 and 52 were 70.0% and 60.0%, respectively. The ORR at Week 26 was 100% (all 3 patients) in patients with non-severe AA and 57.1% (4/7) in patients with severe AA. Among transfusion-dependent patients, 66.7% (4/6) and 62.5% (5/8) became red blood cell- and platelet-transfusion independent, respectively. The most common adverse events were nausea and headache. No deaths or hematologic malignancies were reported. A cytogenetic abnormality was reported in one patient. Conclusion This study confirmed the clinical benefit of eltrombopag plus rabbit-ATG/CsA in IST-naive patients with non-severe or severe AA in Japan.

Identification of living undocumented individuals highlights the need for accurate, precise, and reproducible age estimation methods, especially in those cases involving minors. However, when their country of origin is unknown, or it can be only roughly estimated, it is extremely difficult to apply assessment policies, procedures, and practices that are accurate and child-sensitive. The main aim of this research is to optimize the correct classification of adults and minors by establishing new cut-off values for four different continents (Africa, America, Asia, and Europe). For this purpose, a vast sample of 10,701 orthopantomographs (OPTs) from four continents was evaluated. For determination and subsequent validation of the new third molar maturity index (I

The Bayesian approach is being a fundamental tool in forensic and legal field where inferences and decisions are made. In this study, a full Bayesian calibration model was developed to make probabilistic inferences about age estimation in a reference sample of 891 periapical X-rays of upper and lower canines. These teeth belonged to both deceased and living adult subjects, aged between 20 and 86 years, coming from five different countries (Turkey, Italy, Portugal, Japan and Mexico). For this purpose, the narrowing of pulp chamber due to the apposition of secondary dentine was analysed by means of the pulp/tooth area ratio. To determine the agreement of the method, intra- and inter-observer differences for measuring process were calculated by means of the intraclass correlation coefficient (ICC) analysis. Observer error tests showed excellent agreement between observers and between repeated assessments. According to the results of the ANCOVA, neither nationality nor sex was associated to the secondary dentine apposition while it is associated with individual’s age. The results of the present study indicated that the concept of probability is intrinsically linked to the assessment of age in a forensic context, and the Bayesian approach could be considered a robust tool to overtake the bias generated by traditional regression models, thus helping the decision-making process in a legal framework.

Background Bile leakage is the most common postoperative complication associated with hepatobiliary and pancreatic surgery. Until now, however, a rapid, accurate diagnostic method for monitoring intraoperative and postoperative bile leakage had not been established. Method Bilirubin levels in drained abdominal fluids collected from 23 patients who had undergone hepatectomy (n = 22) or liver transplantation (n = 1) were measured using a microplate reader with excitation/emission wavelengths of 497/527 nm after applying 5 µM of UnaG to the samples. UnaG was also sprayed directly on hepatic raw surfaces in swine hepatectomy models to identify bile leaks by fluorescence imaging. Results The bilirubin levels measured by UnaG fluorescence imaging showed favorable correlations with the results of the conventional light-absorptiometric methods (indirect bilirubin: rs = 0.939, p p Conclusion Fluorescence imaging techniques using UnaG may enable real-time identification of bile leaks during hepatectomy and on-site rapid diagnosis of bile leaks after surgery.

Identification of living undocumented individuals highlights the need for accurate, precise, and reproducible age estimation methods, especially in those cases involving minors. However, when their country of origin is unknown, or it can be only roughly estimated, it is extremely difficult to apply assessment policies, procedures, and practices that are accurate and child-sensitive. The main aim of this research is to optimize the correct classification of adults and minors by establishing new cut-off values for four different continents (Africa, America, Asia, and Europe). For this purpose, a vast sample of 10,701 orthopantomographs (OPTs) from four continents was evaluated. For determination and subsequent validation of the new third molar maturity index (I3M) cut-off values by world regions, a cross-validation by holdout method was used and contingency tables (confusion matrices) were generated. The lower third molar maturity indexes, from both left and right side (I3ML and I3MR) and the combination of both sides (I3ML_I3MR) were calculated. The new cut-off values, that aim to differentiate between a minor and an adult, with more than 74.00% accuracy for all populations were as follows (I3ML; I3MR; I3ML_I3MR, respectively): Africa = (0.10; 0.10; 0.10), America = (0.10; 0.09; 0.09), Asia = (0.15; 0.17; 0.14), and Europe = (0.09; 0.09; 0.09). The higher sensitivity (Se) was detected for the I3ML for male African people (91%) and the higher specificity (Sp) of all the parameters (I3ML; I3MR; I3ML_I3MR) for Europeans both male and female (> 91%). The original cut-off value (0.08) is still useful, especially in discriminating individuals younger than 18 years old which is the goal of the forensic methods used for justice.

This study aimed to examine the applicability of Willems' and Lee's methods in a Japanese population and to find the differences in teeth development between Japanese and Korean children by comparing the accuracy of their estimated age using the two methods. The developmental status of the lower left permanent teeth in 1,475 orthopantomograms of Japanese children were evaluated based on Demirjian's criteria, and the ages were estimated using Willems' and Lee's methods. The errors in estimated ages were calculated and compared with equivalent Korean population data. The accuracy of both methods for estimating the age of the Japanese population was similar to that in the Korean population except for that of Lee's method used in Japanese males. The results showed that there might be differences in teeth development between the Japanese and Korean boys. To increase the accuracy of the dental age estimation, the method that is derived from their own population data should be applied in forensic practice.

SUMMARY The processes that control where higher eukaryotic cells initiate DNA replication throughout the genome are not understood clearly. In metazoans, the Treslin-MTBP complex mediates critical final steps in formation of the activated replicative helicase prior to initiation of replication. Here, we map the genome-wide distribution of the MTBP subunit of this complex in human cells. Our results indicate that MTBP binds to at least 30,000 sites in the genome. A majority of these sites reside in regions of open chromatin that contain transcriptional-regulatory elements (e.g., promoters, enhancers, and super-enhancers), which are known to be preferred areas for initiation of replication. Furthermore, many binding sites encompass two genomic features: a nucleosome-free DNA sequence (e.g., G-quadruplex DNA or AP-1 motif) and a nucleosome bearing histone marks characteristic of open chromatin, such as H3K4me2. Taken together, these findings indicate that Treslin-MTBP associates coordinately with multiple genomic signals to promote initiation of replication., Graphical Abstract, In Brief Kumagai and Dunphy show that Treslin-MTBP, activator of the replicative helicase, binds to at least 30,000 sites in the human genome. Many sites contain a nucleosome with active chromatin marks and nucleosome-free DNA (G-quadruplex or AP-1 site). Thus, Treslin-MTBP associates with multiple genomic elements to promote initiation of DNA replication.

Left ventricular (LV) remodeling with aortic stenosis (AS) appears to differ according to sex, but reverse remodeling after transcatheter aortic valve implantation (TAVI) has not been elucidated in a Japanese population. This study aims to determine whether any sex-related differences in LV or reverse remodeling after TAVI exist in the context of severe AS.Of 208 patients who received TAVI for severe AS in our institution, 100 (men, 42; mean age, 83.0 ± 4.9 years) underwent transthoracic echocardiography before and 3 months after TAVI. Despite similar valvular gradients, women with severe AS had lower indexed LV mass (LVMi) than did men (152.3 ± 35.4 versus 173.2 ± 44.6 g/m2, P = 0.005), with smaller indexed LV end-diastolic (LVEDVi) (50.2 ± 13.3 versus 61.4 ± 20.7 mL/m2, P = 0.001) and end-systolic (LVESVi; 17.9 ± 8.7 versus 24.3 ± 13.8 mL/m2, P = 0.006) volumes. After TAVI, women (-6.0% ± 14.4%) had higher reduction in the rate of change of relative wall thickness (RWT) than did men (4.4% ± 19.0%, P = 0.003). Men (-8.9% ± 3.9%) had higher reduction in the rate of change of LVEDVi than did women (1.5% ± 3.3%, P = 0.045). Incidence of LV reverse remodeling defined as a reduction in LVESV of >15% was significantly higher in men (50%) than in women (26%, P = 0.013).In addition to sex differences in the pattern of LV remodeling with AS, reverse LV remodeling after TAVI also differed between sexes.

Cell cycle-dependent redox changes can mediate transient covalent modifications of cysteine thiols to modulate the activities of regulatory kinases and phosphatases. Our previously reported finding that protein cysteine oxidation is increased during mitosis relative to other cell cycle phases suggests that redox modifications could play prominent roles in regulating mitotic processes. The Aurora family of kinases and their downstream targets are key components of the cellular machinery that ensures the proper execution of mitosis and the accurate segregation of chromosomes to daughter cells. In this study, X-ray crystal structures of the Aurora A kinase domain delineate redox-sensitive cysteine residues that, upon covalent modification, can allosterically regulate kinase activity and oligomerization state. We showed in both Xenopus laevis egg extracts and mammalian cells that a conserved cysteine residue within the Aurora A activation loop is crucial for Aurora A activation by autophosphorylation. We further showed that covalent disulfide adducts of this residue promote autophosphorylation of the Aurora A kinase domain. These findings reveal a potential mechanistic link between Aurora A activation and changes in the intracellular redox state during mitosis, as well as provide insights into how novel small molecule inhibitors may be developed to target specific subpopulations of Aurora A.

Objective to re-examine measures to prevent oral mucositis caused by drugs in head and neck cancer patients during cancer treatment by measuring salivary excretion of 5-fluorouracil. Saliva, blood, and urine were simultaneously collected from oral cancer patients and breast cancer patient at the point in time of before, during, and after the administration of 5-FU, then the 5-FU levels of the samples were quantitatively analysed using LC-MS/MS. In all patients, the 5-FU levels in saliva and serum peaked at 30 min to 3 h after the start of 5-FU treatment, and high levels were maintained throughout the administration of the drug. With regard to urinary 5-FU levels, they remained high from 3 to 120 h after the start of 5-FU treatment. After the completion of 5-FU treatment, even though it not appeared in the patients’ serum and urine promptly, 5-FU was detected in saliva at 12 h after the completion of 5-FU treatment in one oral cancer patient and at 48 h after the completion of 5-FU treatment in the breast cancer patient. It was suggested that the level of hydration after the completion of chemotherapy may be involved in the differences in 5-FU excretion.

We experienced a rare case, which was distant organ metastatic squamous cell carcinoma (SCC) and had deteriorated rapidly. An 80-year-old man was transported to hospital because of a sudden loss of consciousness. A tumor was found in his right mandibular gingiva, which was histopathologically diagnosed as SCC. A large tumor was detected in the pelvic soft tissue on a thoracoabdominal computed tomography scan. The patient died on the 22nd day after he was admitted to hospital. We performed an autopsy. The autopsy revealed multiple distant organ metastases, and all of the lesions were histopathologically diagnosed as SCC.

The present study of two case reports of the victims of the Great East Japan Earthquake demonstrates the effectiveness and limitations of using dental cone-beam computed tomography (CBCT) imaging of cremains as a means of identification. In case 1, identification was assisted by further expanding the age range of the cremains evaluated on macroscopy by obtaining CBCT images of the cremated maxilla. The findings of case 2 presented the possibility that the deceased and the candidate were the same person by superimposing the CBCT images of the cremated patella on the X-ray of the candidate. However, since cremated bones are deformed to varying degrees, it is clear that the images obtained before, rather than after, cremation are more effective in comparing post-mortem and ante-mortem images. Thus, it is necessary to collect extensive and diverse data on the deceased before cremation.

MTBP, the partner of Treslin, contains a novel DNA-binding domain that associates with double-stranded DNA and G-quadruplex DNA. Mutants of MTBP that lack a functional version of this domain cannot support normal initiation of DNA replication., Treslin, which is essential for incorporation of Cdc45 into the replicative helicase, possesses a partner called MTBP (Mdm2-binding protein). We have analyzed Xenopus and human MTBP to assess its role in DNA replication. Depletion of MTBP from Xenopus egg extracts, which also removes Treslin, abolishes DNA replication. These extracts be can rescued with recombinant Treslin-MTBP but not Treslin or MTBP alone. Thus, Treslin-MTBP is collectively necessary for replication. We have identified a C-terminal region of MTBP (the CTM domain) that binds efficiently to both double-stranded DNA and G-quadruplex (G4) DNA. This domain also exhibits homology with budding yeast Sld7. Mutants of MTBP without a functional CTM domain are defective for DNA replication in Xenopus egg extracts. These mutants display an impaired localization to chromatin and the inability to support loading of Cdc45. Human cells harboring such a mutant also display severe S-phase defects. Thus, the CTM domain of MTBP plays a critical role in localizing Treslin-MTBP to the replication apparatus for initiation.

Background Increasing attention is being paid to the left atrial appendage (LAA) in the context of risk stratification in cardioembolic stroke (CES) and the requirement for meticulous planning of percutaneous closure device implantation. However, detailed systematic assessment of the LAA remains limited. Methods This study evaluated the anatomy and function of LAA using 3-dimensional transesophageal echocardiography (3D-TEE) on 194 consecutive patients older than 50 years old hospitalized exclusively for CES. Patients were stratified into 3 groups on the basis of cardiac rhythm: (1) chronic atrial fibrillation (AF), n = 53; (2) paroxysmal AF, n = 26; and (3) no detected AF, n = 115. Results Significant differences between the groups were observed for anatomical (orifice area [OA], depth, diastolic volume) and functional parameters (ejection fraction [EF], flow velocity [FV]), as measured by 3D-TEE. The anatomical parameters were consistently the greatest, and functional parameters were the poorest, in the group with chronic AF. There were significant inverse correlations between them (r = −.33, P = .0003 for depth and EF; r = −.27, P = .0020 for depth and FV; r = −.22, P = .016 for OA and EF; and r = −.38, P Conclusions LAA morphology and function were strongly affected by cardiac rhythm disturbances. Patients with chronic AF had the greatest LAA dimensions, areas, and volumes as well as the lowest LAA functions. An inverse correlation was observed between LAA size and function.

Hydrolyzed proteins are often prescribed for dogs with food hypersensitivity in food elimination programs. However, the potential of these diets to stimulate lymphocyte-mediated hypersensitivity is currently unknown. In this study, two commercially available hydrolyzed diets for dogs, D-1 (Aminopeptide Formula Dry, Royal Canin Japon, Tokyo, Japan), and D-2 (Canine z/d Ultra Dry, Hill's-Colgate (Japan) Ltd., Tokyo, Japan), were analyzed to identify residual proteins or peptides, as well as activated helper T-lymphocyte reactions in dogs with suspected food hypersensitivity. Proteins and peptides with molecular weights >1 kDa (majority 1.5-3.5 kDa) were detected in both diet extracts with sodium dodecyl sulfate polyacrylamide gel electrophoresis, and size exclusion chromatography. When peripheral blood mononuclear cells (PBMC's) from 316 dogs with suspected food allergies were cultured with hydrolyzed diet extracts, flow cytometry analysis revealed detectable levels of CD25low helper T-lymphocytes stimulated by D-1 and D-2 in 91 of 316, (28.8%), and 75 of 316 (23.7%) samples, respectively. These data indicated that the extracts contained proteins or peptides large enough to activate the lymphocytes. The percentages of CD25low helper T-lymphocytes stimulated by D-1 and D-2 extracts increased to 38.7% and 29.6%, respectively, in 186 of the original 316 samples (186/316, 58.9%), also reactive to poultry-related antigens. Thus, both poultry-related antigens, and D-1 and D-2 diet extracts may activate helper T-lymphocytes. These results demonstrate that hydrolyzed diets may contain proteins that stimulate helper T-lymphocytes, and may not be effective for treating all dogs with food hypersensitivity.

Besides TopBP1, ETAA1 has been identified more recently as an activator of the ATR-ATRIP complex in human cells. We have examined the role of ETAA1 in the Xenopus egg-extract system, which has been instrumental in the study of ATR-ATRIP. Depletion of ETAA1 from egg extracts did not noticeably reduce the activation of ATR-ATRIP in response to replication stress, as monitored by the ATR-dependent phosphorylation of Chk1 and RPA. Moreover, lack of ETAA1 did not appear to affect DNA replication during an unperturbed S-phase. Significantly, we find that TopBP1 is considerably more abundant than ETAA1 in egg extracts. We proceeded to show that ETAA1 could support the activation of ATR-ATRIP in response to replication stress if we increased its concentration in egg extracts by adding extra full-length recombinant ETAA1. Thus, TopBP1 appears to be the predominant activator of ATR-ATRIP in response to replication stress in this system. We have also explored the biochemical mechanism by which ETAA1 activates ATR-ATRIP. We have developed an in vitro system in which full-length recombinant ETAA1 supports activation of ATR-ATRIP in the presence of defined components. We find that binding of ETAA1 to RPA associated with single-stranded DNA (ssDNA) greatly stimulates its ability to activate ATR-ATRIP. Thus, RPA-coated ssDNA serves as a direct positive effector in the ETAA1-mediated activation of ATR-ATRIP.

PURPOSE: To develop and validate a CT diagnostic algorithm for bicuspid aortic valve (BAV) classification. MATERIALS AND METHODS: This retrospective study included 212 consecutive patients with severe aortic stenosis who underwent CT followed by aortic valve replacement (mean age, 71 years [range, 27–93 years]; 125 women; 37% with a BAV) from 2012 to 2017. BAV diagnosis and BAV category were determined by using the CT diagnostic algorithm developed and were compared with those attained through surgical diagnosis. Reproducibility and agreement were assessed using the Cohen kappa (κ) coefficient. The value of adding CT to age, aortic diameter index, and transthoracic echocardiography (TTE) was evaluated by using the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and decision-curve analysis. RESULTS: Intra- and interobserver reproducibility were good or excellent for all CT diagnoses (κ ≥ 0.6 for all). Agreement between CT and surgical diagnoses was excellent (κ = 0.90) for BAV detection and good (κ = 0.69) for BAV categorization. Sixteen percent (five of 31) of patients with functional BAV diagnosed by using CT received a diagnosis of congenital BAV at surgery. The addition of CT to age, aortic diameter, and TTE showed a higher AUC (with CT, 0.97 [95% CI: 0.91, 0.99] vs without CT, 0.91 [95% CI: 0.85, 0.95]; P = .003) and NRI (1.79 [95% CI: 1.65, 1.92], P < .001) and a higher net benefit among all BAV probabilities. CONCLUSION: CT diagnosis was consistent with surgical diagnosis and had an additive value over traditional diagnostic methods; however, there was a risk of overlooking congenital BAV in patients with functional BAV diagnosed by using CT. Supplemental material is available for this article. © RSNA, 2021

The synthesis of multifunctional nano-sized materials is leading to the rapid development of key application, including improved drug delivery, bioimaging and protein separation. In this work, magnetic silica particles modified with novel guanidine containing co-polymers were manufactured via sol-gel method. To evaluate the chemical composition of our prepared samples, FT-IR spectroscopy and thermogravimetry were conducted. Scanning electron microscopy was used in order to investigate the morphology of final products after modification by guanidine containing co-polymers and iron nanoparticles. In addition, the surface of polymer-silica composites was functionalized by the novel bilirubin-inducible fluorescent protein UnaG. In an aqueous bilirubin solution, the silica particles decorated with the polymer-UnaG have showed bright fluorescence. Synthesis and characterization of these hybrid materials allow developing of new multifunctional nano-sized materials, which will be used for detection and separation of bilirubin, a lipophilic heme catabolite that is a clinical diagnostic for liver function.

Aims To evaluate the cut-off value of third molar maturity index (I3M) = 0.08 for discriminating minors from adults in Japanese population. Material and Methods 276 panoramic radiographs of healthy Japanese subjects (139 girls and 137 boys) age range from 14 to 24 years were evaluated. Results ICC (Intra-class correlation coefficient) for intra-rater and inter-rater agreement of I3M was 99.6% (95% CI 98.6–99.9%) and 98.9% (95% CI 98.8–99.9%) respectively. The proportion of correctly classified in girls was 87% (95% CI 81–93%) and in boys was 91% (95% CI 87–96%). The sensitivity of the test in girls and boys was 84% (95% CI 77–92%) and 89% (95% CI 83–95%) respectively and specificity was 93% (95% CI 85–100%) and 96% (95% CI 90–100%) in girls and in boys. The PPV (Positive Predictive Value) was 87% (95% CI 69–95%) in girls and 92% (95% CI 74–98%) in boys. Conclusion The results of the study show that I3M is capable of discriminating adults and minors in subjects around legal age of 18 years old in Japanese population.

Improved age estimates may result from combining different age predictors. This study aimed to validate age estimation performances combining the radiographic development of teeth, cervical vertebrae, hand and wrist bones, skull, and mandible. The sampled consisted of 256 individuals aged between 4 and 20 years. Bayes' rule with a multivariate continuation ratio model was applied for the distribution of the dental scores. The additional age information of the skeletal variables was assessed extending the dental model separately and combining the variables. The performances of all models were quantified and compared using mean error (ME), mean absolute error (MAE), and root mean squared error (RMSE). The best performance resulted combining all variables (ME - 0.04 for F and M; MAE 0.91 for F and 0.95 for M; RMSE 1.14 for F and 1.19 for M). To improve performances and minimize radiation doses, the combination of teeth and hand and wrist bones information is recommended. ispartof: INTERNATIONAL JOURNAL OF LEGAL MEDICINE vol:132 issue:6 pages:1-9 ispartof: location:Germany status: Published online

Non-ionic surfactants have raised a considerable interest for solubilization, encapsulation, permeabilization and controlled release of various compounds due to their unique physicochemical properties. Nevertheless, it is still challenging to create convenient self-assembled multifunctional materials with high solubilization and encapsulation capacities by preserving their advanced capabilities to protect loaded cargos without altering their characteristics. In this work, we present an extended concept of micellar clusters (MCs) formation based on partial entrapment and stabilization of chelate ligands by hydrophobic forces found on the non-ionic surfactant micelle interface of the Triton-X family (TX-100/TX-114), followed by subsequent complexation of the preformed structures either by metal ions or a supporting chelator. The formation aspects, inner structure and the role of external factors such as the addition of competitive ligands have been extensively studied. MCs loaded by hydrophobic fluorescent compounds with high encapsulation efficiency demonstrate an excellent optical response in aqueous media without crystallization as well as sufficient increase in solubility of toxic hydrophobic compounds such as bilirubin (>50 times compared to pure surfactants). Furthermore, Triton-X-based MCs provide a unique feature of selective permeability to hydrophilic ligand-switching proteins such as UnaG and BSA demonstrating bright “turn-on” fluorescence signal either inside the cluster or on its interface via complexation. The proposed strategies allowed us to successfully encapsulate and visualize a newly synthesized, highly hydrophobic anticancer PTR-58-CLB-CAMP peptide drug, while MCs loaded by the drug exhibit a considerable antitumor activity against HeLa cells.

Treslin helps to trigger the initiation of DNA replication by promoting integration of Cdc45 into the replicative helicase. Treslin is a key positive-regulatory target of cell-cycle control mechanisms; activation of Treslin by cyclin-dependent kinase is essential for the initiation of replication. Here we demonstrate that Treslin is also a critical locus for negative regulatory mechanisms that suppress initiation. We found that the checkpoint-regulatory kinase Chk1 associates specifically with a C-terminal domain of Treslin (designated TRCT). Mutations in the TRCT domain abolish binding of Chk1 to Treslin and thereby eliminate Chk1-catalyzed phosphorylation of Treslin. Significantly, abolition of the Treslin-Chk1 interaction results in elevated initiation of chromosomal DNA replication during an unperturbed cell cycle, which reveals a function for Chk1 during a normal S phase. This increase is due to enhanced loading of Cdc45 onto potential replication origins. These studies provide important insights into how vertebrate cells orchestrate proper initiation of replication.

The purpose of our research is to identify causative metals by using particle-induced X-ray emission (PIXE) method to directly analyze trace elements in the oral mucosa with oral lichen planus (OLP). Subjects were 72 patients with OLP, and the patients are 25 men and 47 women, with a mean age of 60.1 years (OLP group). The control is elemental analysis data by PIXE method of 100 cases of the oral mucosa of healthy persons (control group). Seventeen essential elements and 12 contaminating elements were detected from the oral mucosa of the OLP and control groups. As to appearance ratio of elements in oral mucosa, among the contaminating elements, levels of Al, Ga, Sb, Hg and Pb were significantly lower, whereas Au and Y were significantly higher in the OLP group than in the control group. About concentration of elements in oral mucosa, the contaminating elements in the oral mucosa of the OLP group had a lower appearance ratio than in the control but each of the contaminating elements was more abundant. Among 25 subjects in the OLP group and seven in the control group, serum, oral mucosa and saliva were collected from the same individual. Abundance in serum and saliva varied depending on the element, but in general, a tendency was seen for contaminating elements to be more abundant in saliva than in serum and for essential elements to be more abundant in serum than in saliva.

We encountered a patient with a huge osteoma extending over half of the mandible, which was incidentally discovered on a head-and-neck computed tomography (CT) by an otolaryngological examination for vertigo. A tumorous lesion of the right mandible was noted, and the patient was referred to our department. The tumor extended from the median mandible over the right anterior margin of the ramus of the mandible. To improve the abnormal intraoral morphology, tumor resection and orthopedic surgery were performed. The histopathological diagnosis was a cancellous osteoma. Dentures were attached after surgery, and the postoperative course has been favorable with no tumor re-enlargement.

CKS proteins are small (9-kDa) polypeptides that bind to a subset of the cyclin-dependent kinases. The two paralogs expressed in mammals, Cks1 and Cks2, share an overlapping function that is essential for early development. However, both proteins are frequently overexpressed in human malignancy. It has been shown that CKS protein overexpression overrides the replication stress checkpoint, promoting continued origin firing. This finding has led to the proposal that CKS protein-dependent checkpoint override allows premalignant cells to evade oncogene stress barriers, providing a causal link to oncogenesis. Here, we provide mechanistic insight into how overexpression of CKS proteins promotes override of the replication stress checkpoint. We show that CKS proteins greatly enhance the ability of Cdk2 to phosphorylate the key replication initiation protein treslin in vitro. Furthermore, stimulation of treslin phosphorylation does not occur by the canonical adapter mechanism demonstrated for other substrates, as cyclin-dependent kinase (CDK) binding-defective mutants are capable of stimulating treslin phosphorylation. This effect is recapitulated in vivo, where silencing of Cks1 and Cks2 decreases treslin phosphorylation, and overexpression of wild-type or CDK binding-defective Cks2 prevents checkpoint-dependent dephosphorylation of treslin. Finally, we provide evidence that the role of CKS protein-dependent checkpoint override involves recovery from checkpoint-mediated arrest of DNA replication.

Although paroxysmal atrial fibrillation (PAF) is an important cause of cardioembolic stroke, in contrast to chronic AF patients, the anatomical features of the left atrial appendage (LAA) in PAF patients remain unknown. Here, we investigated differences in LAA structures in patients with PAF and those with normal sinus rhythms (NSR) using 3D-computed tomography (3D-CT), which allows us to visualize complicated LAA structures at high spatial resolution. Study subjects were 30 consecutive PAF and 30 NSR patients with complete enhanced cardiac 3D-CT images available. After reconstruction of 3D LAA images, anatomical parameters of the LAA were measured and compared according to three proposed definitions of the LAA orifice plane determined by the following anatomical landmarks: DEF#1, center of warfarin ridge and centerline of proximal left circumflex artery; DEF#2, slope of warfarin ridge and mitral valve annulus; DEF#3, observers’ discretion by progressive rotation using the observers’ best estimate without the use of landmarks. The LAA volumes of the PAF groups were significantly greater than the NSR group according to all 3 definitions (DEF#1: 1.43 times, DEF#2: 1.44 times, and DEF#3: 1.36 times greater). The LAA orifice area was significantly larger in PAF than in NSR according to DEF#2, but was similar by DEF#1 and DEF#3. Intra-observer and inter-observer variations for any LAA measurements were very low. In conclusion, 3D-CT-based quantitative assessment of the LAA provides highly reproducible and detailed measurements, which can successfully discriminate differences of LAA volume between patients with NSR and those with PAF, suggesting significantly greater volumes in the latter.

UnaG is a recently discovered ligand-induced fluorescent protein that utilizes bound bilirubin (BR) as its fluorophore. The fluorescence of the UnaG-BR complex (holoUnaG) compares in quantum efficiency to that of enhanced green fluorescent protein, but it is superior in that the fluorophore formation is instantaneous and not dependent on oxygen; hence, much attention has been paid to UnaG as a new fluorescent probe. However, many important molecular properties of fluorescent probes remain unknown, such as the association/dissociation rates of BR, which determine the stability thereof, and the dispersibility of UnaG in aqueous solutions, which influence the functions of labeled proteins. In this study, we found, in the process of investigating the association rate, that the holoUnaG takes two distinct fluorescence states, which we named holoUnaG 1 and holoUnaG 2 . The holoUnaG 1 initially forms after binding BR and then changes to the brighter holoUnaG 2 by a reversible intra-molecular reaction, thereby finally reaching an equilibrium between the two states. Spectroscopic analysis indicated that the intra-molecular reaction was associated not with a chemical change of BR but with a change in the environmental conditions surrounding BR. We also revealed that the molecular brightness ratio and equilibrium population ratio of the two states (holoUnaG 1 /holoUnaG 2 ) were 1:3.9 and 6:4, respectively, using photon number counting analysis. From these results, we have suggested a novel schema, to our knowledge, for the formation of the UnaG and BR complex system and have determined the various rate constants associated therein. Additionally, using analytical ultracentrifugation, we established that UnaG in the apo-state (apoUnaG) and the holoUnaG are monomeric in aqueous solution. These findings provide not only key information for the practical use of UnaG as a fluorescent probe, but also the possibility for development of a brighter UnaG mutant by genetic engineering to constitutive holoUnaG 2 .