Novel transcriptional regulator OxtR1 regulates potential ferrodoxin in response to oxygen stress in Treponema denticola.

OBJECTIVE: Treponema denticola has been strongly implicated in the pathogenesis of chronic periodontitis. Previously, we reported that the potential transcriptional regulator TDE_0259 (oxtR1) is upregulated in the bacteriocin ABC transporter gene-deficient mutant. OxtR1 may regulate genes to adapt to environmental conditions during colonization; however, the exact role of the gene in T. denticola has not been reported. Therefore, we investigated its function using an oxtR1-deficient mutant. METHODS: The growth rates of the wild-type and oxtR1 mutant were monitored under anaerobic conditions; their antibacterial agent susceptibility and gene expression were assessed using a liquid dilution assay and DNA microarray, respectively. An electrophoretic mobility shift assay was performed to investigate the binding of OxtR1 to promoter regions. RESULTS: The growth rate of the bacterium was accelerated by the inactivation of oxtR1, and the mutant exhibited an increased minimum inhibitory concentration against ofloxacin. We observed a relative increase in the expression of genes associated with potential ferrodoxin (TDE_0260), flavodoxin, ABC transporters, heat-shock proteins, DNA helicase, iron compounds, and lipoproteins in the mutant. OxtR1 expression increased upon oxygen exposure, and oxtR1 complementation suppressed the expression of potential ferrodoxin. Our findings also suggested that OxtR1 binds to a potential promoter region of the TDE_0259-260 operon. Moreover, the mutant showed a marginal yet significantly faster growth rate than the wild-type strain under H2O2 exposure. CONCLUSION: The oxygen-sensing regulator OxtR1 plays a role in regulating the expression of a potential ferrodoxin, which may contribute to the response of T. denticola to oxygen-induced stress.

Design of closed loop for reproduction of gas-dominated hydrate flow.

The study presents a novel setup for measuring the flow regime of hydrate particles in a gas-dominated flow, which is of interest for applications such as natural gas transportation. A closed-flow loop, driven by a novel internal fan, enables continuous observation of hydrate particle behavior in a gas flow. The experimental setup allows the production and insertion of HFC134a gas hydrate particles with diameters of 10-50 µm into the gas flow loop via a bypass loop. The performance curve of the internal fan is validated, and its suitability for achieving the required flow speed (5 m/s) is demonstrated. Through an observation window using camera systems, the flow regime of glass beads is successfully visualized and analyzed. To validate the experimental data, a coupled computational fluid dynamics-discrete element method model is used to simulate the particle flow density distribution. The study findings demonstrate the effectiveness of the experimental setup in characterizing the flow regime of hydrate particles in a gas-dominated flow.

Fragility and long-term clinical outcomes in patients with venous thromboembolism receiving direct oral anticoagulants: From the COMMAND VTE REGISTRY-2.

INTRODUCTION: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE). MATERIALS AND METHODS: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg. RESULTS: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41). CONCLUSIONS: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE.

Management of pulmonary hemodynamics prior to delivery in a pregnant woman with development of decompensated pulmonary arterial hypertension.

Prompt termination of pregnancy in patients with decompensated pulmonary arterial hypertension (PAH) is imperative for improvement of maternal hemodynamics, but such termination may also result in maternal death due to further deterioration of PAH immediately after delivery. However, there have been limited reports on whether implementation of PAH therapy with continuation of pregnancy improves the maternal outcome, especially in treatment-naïve patients with PAH. A 24-year-old woman was admitted to our hospital with a chief complaint of dyspnea (WHO functional class IV) at 22 weeks and 3 days of gestation. She was diagnosed with PAH accompanied by right heart failure and low cardiac output. Intensive treatment was initiated with inotropic agents, oxygen therapy, and PAH therapy, resulting in improvement of her hemodynamics. A caesarean section was performed at 23 weeks and 3 days. Although her pulmonary arterial pressure transiently increased with oxygenation deteriorating immediately after delivery, worsening PAH improved without mechanical circulatory support. She continued receiving pulmonary vasodilators without relapse of pulmonary hypertension for three years. The improvement of pulmonary hemodynamics prior to delivery with PAH therapy led to a favorable outcome after delivery. Learning objective: Pulmonary hemodynamics in pregnant patients with pulmonary arterial hypertension (PAH) can deteriorate with the continuation of pregnancy, while termination can also cause PAH surge immediately after delivery. In treatment-naïve patients with PAH, who are most likely to benefit from PAH therapy, implementation of PAH therapy with continuation, even with a decompensated status, may improve the hemodynamics prior to delivery, resulting in a favorable outcome after delivery.

Ideal insertion point and projection of the infra-acetabular screw in acetabular fracture surgery.

BACKGROUND: In acetabular fracture surgery, an infra-acetabular screw (IAS) is inserted from the anterior to the posterior column through the infra-acetabular corridor to stabilize both columns. Although the IAS is useful for increasing fixation strength, proper placement requires proficiency and often results in extraosseous screw penetration. The complex anatomy of the infra-acetabular corridor and difficult intraoperative detection of the ideal insertion point and angle make proper placement of the IAS challenging. This study aimed to detect the ideal insertion point and angle of the IAS based on anatomical landmarks that can be directly identified intraoperatively. METHODS: We retrospectively reviewed the pelvic CT of 50 adults who underwent serial slice CT imaging. The pelvic inlet plane (PIP), which contains the anterior border of both the sacroiliac joint and posterior superior edge of the pubic symphysis, was used as the reference plane for the pelvic coordinate system to simulate the ideal insertion of IAS. The distance from the posterior superior edge of the pubic symphysis to the ideal insertion point of the IAS (IAS distance) and the angle and length of the IAS that could be inserted from the ideal insertion point were measured. RESULTS: The mean IAS distance was 61.0 ± 5.7 mm (57.6 ± 4.3 mm in men and 64.4 ± 4.9 mm in women). The mean angle between ideal IAS and yz-plane on the outlet view (α-angle) was 8.4 ± 6.6 ° (6.4 ± 5.6° in men and 10.5 ± 7.0° in women). The mean angle between ideal IAS and y-axis on the yz-plane (ß-angle) was 86.5 ± 10.6 ° (86.0 ± 10.3° in men and 87.0 ± 10.9° in women). The length of IAS was 97.1 ± 4.7 mm in men and 89.2 ± 3.6 mm in women. CONCLUSION: The IAS ideal insertion point detected as a distance from the pubic symphysis may aid in the proper insertion of the IAS during surgery. The insertion angle was parallel or tilted 10 ° laterally to the longitudinal axis in the pelvic outlet plane and almost perpendicular to the PIP in the sagittal plane when inserted from the ideal insertion point.

PSmad3+/Olig2- expression defines a subpopulation of gfap-GFP+/Sox9+ neural progenitors and radial glia-like cells in mouse dentate gyrus through embryonic and postnatal development.

In mouse dentate gyrus, radial glia-like cells (RGLs) persist throughout life and play a critical role in the generation of granule neurons. A large body of evidence has shown that the combinatorial expression of transcription factors (TFs) defines cell types in the developing central nervous system (CNS). As yet, the identification of specific TFs that exclusively define RGLs in the developing mouse dentate gyrus (DG) remains elusive. Here we show that phospho-Smad3 (PSmad3) is expressed in a subpopulation of neural progenitors in the DG. During embryonic stage (E14-15), PSmad3 was predominantly expressed in gfap-GFP-positive (GFP+)/Sox2+ progenitors located at the lower dentate notch (LDN). As the development proceeds (E16-17), the vast majority of PSmad3+ cells were GFP+/Sox2+/Prox1low+/Ki67+ proliferative progenitors that eventually differentiated into granule neurons. During postnatal stage (P1-P6) PSmad3 expression was observed in GFP+ progenitors and astrocytes. Subsequently, at P14-P60, PSmad3 expression was found both in GFP+ RGLs in the subgranular zone (SGZ) and astrocytes in the molecular layer (ML) and hilus. Notably, PSmad3+ SGZ cells did not express proliferation markers such as PCNA and phospho-vimentin, suggesting that they are predominantly quiescent from P14 onwards. Significantly PSmad3+/GFP+ astrocytes, but not SGZ cells, co-expressed Olig2 and S100ß. Together, PSmad3+/Olig2- expression serves as an exclusive marker for a specific subpopulation of GFP+ neural progenitors and RGLs in the mouse DG during both embryonic and postnatal period.

The effect of scanning pathways on trueness and precision in full-arch optical impression.

BACKGROUND: In this study, we investigated the effects of differences in scanning pathways during optical impression on the trueness and precision of full-arch impressions. METHODS: Reference data were obtained using a laboratory scanner. All optical impressions were measured across the dental arch using TRIOS® 3 in four different pathways. The reference and optical impression data were superimposed using the best-fit method. The criteria for superimposition were based on the starting side of the dental arch (partial arch best-fit method, PB) and based on the full arch (full arch best-fit method, FB). The data were compared between the left and right molars (starting and ending sides). The scan deviations for trueness (n = 5) and precision (n = 10) were obtained for each group by calculating the root mean square (RMS) of the deviation at each measurement point. Visual observations using superimposed color map images revealed variations in trueness. RESULTS: There were no significant differences in scanning time or amount of scan data between the four scanning pathways. Trueness did not differ significantly among the four pathways with respect to the starting and ending sides, regardless of the superimposition criteria. Precision with PB was significantly different between scanning pathways A and B, and pathways B and C for the starting sides, and between scanning pathways A and B, and pathways A and D for the ending sides. In contrast, there was no significant difference between the starting and ending side in pathways for FB. Regarding PB, color map images showed a large error range in the direction toward the molar radius for the occlusal surface and cervical regions on the ending sides. CONCLUSION: Differences in the scanning pathways did not affect trueness, regardless of the superimposition criteria. On the other hand, differences in the scanning pathways affected the precision of the starting and ending sides with PB. Scanning pathways B and D were more precise on the starting and ending sides, respectively.

Managing periprosthetic tibia fractures: International perspectives.

Knee arthroplasty, both total knee and unicompartmental, has had a significant impact on millions of patients globally. Although satisfaction is usually high, complications such as periprosthetic fracture are increasingly common. Distal femur periprosthetic fractures are relatively well researched and understood in comparison with periprosthetic proximal tibia fractures (PTFs). The management of PTFs is essentially an evidence-free area. This review explores the literature (or lack thereof) and integrates cases from Australia and Japan. As it stands, there is scant literature relating to all facets of PTFs, including, most concerningly, the management of them. Larger studies are required to help further investigate this important interface between arthroplasty and orthopaedic trauma. As a guide, those with loose prostheses will likely benefit most from revision total knee arthroplasty, while those with well-fixed prostheses can be managad according to the fracture with homage paid to the presence of the prosthesis. The use of periarticular locked plates is likely a better option over conventional large or small fragment plates. Nonoperative management is a viable option for selected individuals and can be associated with favorable outcomes.

Localization and pathogenic role of the cysteine protease dentipain in Treponema denticola.

The Msp protein complex and the serine protease dentilisin are the best-characterized virulence factors in Treponema denticola, the major etiological agent of chronic periodontitis. In addition to these outer sheath factors, the cysteine protease dentipain contributes to pathogenicity, but its secretion, processing, cellular localization, and role in T. denticola virulence are not fully understood. In this study, we found that full-sized dentipain (74-kDa) and the 52-kDa truncated form of the enzyme are located, respectively, in the outer sheath derived from T. denticola dentilisin- and the Msp-deficient mutants. Furthermore, dentipain was barely detected in the wild-type strain. These results suggest that dentilisin and Msp, the major outer sheath proteins, are involved in the secretion and maturation of dentipain. Inactivation of the dentipain gene slowed the growth of T. denticola, and the effect was more profound in serum-free medium than in serum-containing medium. Several genes, including those encoding transporters and methyl-accepting chemotaxis proteins, were differentially expressed in the dentipain-deficient mutant. Furthermore, the mutant strain was more hydrophobic than the wild-type strain. Finally, the mutant showed less autoaggregation activity and adhesion to IgG in a serum-free medium than the wild-type strain. These findings suggest that dentipain contributes to the virulence of T. denticola by facilitating adhesion and acquisition of nutrients essential for colonization and proliferation in the gingival crevice under serum-rich conditions.

The importance of renal function in anemic patients treated with edoxaban after orthopedic surgery in a real-world clinical setting: A retrospective study.

Edoxaban (Edx) has been approved to prevent venous thromboembolism after total knee and/or hip arthroplasty in Japan. However, the risk of anemia with Edx treatment remains elusive. No risk factors for Edx-associated anemia after orthopedic surgery have been reported. This study aimed to clarify the risk of anemia associated with Edx treatment and determine the risk factors for Edx-associated anemia after orthopedic surgery with a high risk for bleeding. First, the association between Edx treatment and the incidence of anemia-related events was retrospectively investigated by pharmacovigilance analyses using data from 5769,866 reports between the first quarters of 2016 and 2020 in the Food and Drug Administration Adverse Event Reporting System and 2752,050 reports between the fourth quarters of 2011 and 2019 in the Japanese Adverse Drug Event Report. Second, 221 patients who underwent Edx treatment after total knee and/or hip arthroplasty between July 2011 and June 2012 at a single center were included in a case-control study to clarify the risk factors for anemia. Edx treatment was associated with an increased risk of anemia-related events in orthopedic patients. Reduced renal function was identified as a critical risk factor for Edx-associated anemia after orthopedic surgery. The present study indicates that renal function should be considered in the risk management of increased Edx-associated anemia after orthopedic surgery.

Analytic Map of Three-Channel S Matrix: Generalized Uniformization and Mittag-Leffler Expansion.

We explore the analytic structure of the three-channel S matrix by generalizing uniformization and making a single-valued map for the three-channel S matrix. First, by means of the inverse Jacobi's elliptic function we construct a transformation from eight Riemann sheets of the center-of-mass energy complex plane onto a torus, on which the three-channel S matrix is represented single-valued. Second, we show that the Mittag-Leffler expansion, a pole expansion, of the three-channel scattering amplitude includes not only topologically trivial but also nontrivial contributions and is given by the Weierstrass zeta function. Finally, taking a simple nonrelativistic effective field theory with contact interaction for the S=-2, I=0, J^{P}=0^{+}, ΛΛ-NΞ-ΣΣ coupled-channel scattering, we demonstrate that as a function of the uniformization variable the scattering amplitude is, in fact, given by the Mittag-Leffler expansion and is dominated by contributions from neighboring poles.

Identifying marine debris source position using adjoint marginal sensitivity method and stranded beach litter data in Singapore.

Movement of marine debris is transboundary and complex, travelling vast distances and accumulating on shorelines. These marine debris wash ashore as stranded beach litter. The objective of this work is to identify release sources of marine debris accumulated along the Singapore coastlines collected by applying a time-backward adjoint marginal sensitivity method and citizen science data of stranded beach litter by a voluntary beach clean-up group. A popular tourist hotspot on the opposite shore was estimated as a possible release source contributing to the marine debris accumulation. This analytical result was validated by population density, industry types, rainfall, and inference from product packaging labels. The use of the citizen science data also illustrated potential as a data source for baseline monitoring and long-term cross-border research that influence policymaking. Future research can be conducted in an expanded domain, considering monsoon effects and instantaneous release events.

Prognostic Impact of Peak Aortic Jet Velocity on Patients With Acute Myocardial Infarction.

BACKGROUND: Aortic valve stenosis (AS) leads to increased cardiovascular mortality and morbidity, and recent studies reported that even mild-to-moderate AS was associated with poor prognosis in the general population. This study investigated the prognostic impact of mild or moderate AS, defined as 2.0 m/s ≤ peak aortic jet velocity (Vmax) ≤3.9 m/s using echocardiography in acute myocardial infarction (AMI) patients.Methods and Results: This study enrolled 3,049 AMI patients using data from the Mie ACS registry. Patients were divided into 2 groups according to Vmax: Group 1: Vmax <2.0 m/s and/or visually intact aortic valve in which all 3 leaflets are fully and evenly open; Group 2: 2.0 m/s ≤ Vmax ≤ 3.9 m/s. There were 2,976 patients in Group 1and 73 patients in Group 2. The Group 2 patients were older, had a higher percentage of males and had lower body mass index and Killip ≥2 than the Group 1 patients. Angiographic data, door-to-balloon time, and mechanical support were not different between the 2 groups. The Group 2 patients demonstrated a significantly higher all-cause mortality rate (P<0.01) and composite of cardiovascular death and heart failure hospitalization (P<0.01), and Kaplan-Meier analysis showed the same tendency in propensity score-matched patients. CONCLUSIONS: The present study revealed that mild or moderate AS based on Vmax is associated with poor prognosis following AMI.

Photodynamic Diagnosis Using 5-Aminolevulinic Acid with a Novel Compact System and Chromaticity Analysis for the Detection of Oral Cancer and High-Risk Potentially Malignant Oral Disorders.

Detecting early-stage oral cancer and precancerous lesions are critical to improving patient prognosis and quality of life after treatment. Photodynamic diagnosis using 5-aminolevulinic acid enables the detection of malignant lesions. This study aimed to improve the diagnostic accuracy of photodynamic diagnosis using an objective chromaticity analysis of fluorescence emitted from oral lesions. Sixty-seven patients with clinically suspicious oral cavity lesions underwent photodynamic diagnosis after topical application of 5-aminolevulinic acid solution, followed by imaging and histological evaluation of the lesions. Chromaticity red and green values were measured from the fluorescence images on the lesion, and the red-to-green ratio was calculated. The photodynamic diagnosis allowed for the visualization of oral cancer and high-risk dysplasia as red fluorescence. Compared to low-risk dysplasia and benign lesions, oral cancer and high-risk dysplasia areas had a significantly higher red value and red-to-green ratio. After setting the cutoff value, sensitivity and specificity were 83.3-88.7% and 83.3-83.9%, respectively, when discriminating between oral cancer or high-risk dysplasia and low-risk dysplasia or benign lesions. Photodynamic diagnosis combined with chromaticity analysis may be a valuable diagnostic tool for detecting oral lesions, with a high likelihood of malignant transformation.

Effects of Cuspal Inclination and Luting Agent on Fracture Load Values in Composite Resin CAD/CAM Crowns.

The purpose of this study was to evaluate whether change in cuspal inclination influences the fracture load values of composite resin computer-aided design/computer-aided manufacturing (CAD/CAM) crowns. Abutment teeth and CAD/CAM crowns were prepared as they would be for treating a mandibular first premolar with two cusps. The CAD/CAM crowns were designed so that 1) the principal stress lines would be radially distributed from the two points of contact with the indenter to the occlusal area of the abutment (Type I), or 2) the principal stress lines would pass outside the occlusal area of the abutment (Types II and III). The CAD/CAM crowns were mounted on the abutments using one of two types of resin or polycarboxylate cement. Fracture load values were measured using a universal tester. The Type I CAD/CAM crowns exhibited the highest mean fracture load value, followed by the Type II crowns and then the Type III crowns, with significant differences seen between all types (p<0.05). The luting agent used (resin or polycarboxylate cement) showed no effect on the fracture load value. With the Type II and Type III crowns, significant differences in the fracture load value were observed between the Super-Bond and Hy-Bond polycarboxylate cement groups (p<0.05).

Sintering distortion of monolithic zirconia in 4-unit fixed partial denture: Effect of layered structure and vertical milling area.

Layered-type zirconia disks, which offer color gradation from enamel to cervical shade, have been employed in recent years to replicate the shades of natural teeth. The layered structure is effective at replicating colors and has helped popularize monolithic zirconia restorations. However, the sintering shrinkage of zirconia is very large; thus, controlling the sintering distortion is very important. Thus, the objective of this study was to determine the influence exerted by the layered structure of the zirconia disk and the vertical milling area on the sintering distortion. An experimental fixed partial denture (FPD) was designed based on a 4-unit monolithic zirconia FPD. A single-composition (SC)-type disk with no shade and a single-composition-layered (SCL)-type disk with shade gradation were selected for this study. In particular, three milling areas, the top end of the disk (area I), vertical center (area II), and bottom end of the disk (area III), were investigated. Moreover, the sintering distortions generated by the experimental FPDs were measured. Results showed that sintering distortion in 4-unit monolithic zirconia FPDs occurred in all SC and SCL areas. Additionally, the sintering distortions were affected by the layered structure of the zirconia disks, the degree of which depended on the milling area (area I > area II > area III). Thus, when fabricating dental prosthesis using SCL zirconia disks, the milling area must be selected considering both the color adjustment and sintering distortion.

Prevalence and Clinical Characteristics of Proximal Deep Venous Thrombosis After a High-Density Coronavirus Disease 2019 Cluster in a Japanese Psychiatric Hospital.

BACKGROUND: The prevalence of deep venous thrombosis (DVT) among hospitalized psychiatric patients after coronavirus disease 2019 (COVID-19) infection remains unclear.Methods and Results:We retrospectively investigated the prevalence of proximal DVT after COVID-19 infection among 50 hospitalized patients in a Japanese psychiatric hospital that in which a COVID-19 cluster developed between August and September 2020. The prevalence of proximal DVT was 10.0%. Patients with proximal DVT had a lower body weight and higher maximum D-dimer levels and International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE scores. CONCLUSIONS: After COVID-19 infection, hospitalized psychiatric patients are at high risk of DVT and should be carefully followed up.

Influence of one-wall remaining coronal tooth with resin abutment and fiber post on static and dynamic fracture resistance.

The objective of this study was to determine the influence of height and thickness of the one wall remaining coronal tooth structure on the fracture resistance of an endodontically treated root with resin abutment build-up using resin composite and fiber-reinforced resin composite post. Static and dynamic fracture tests were performed by placing the remaining tooth wall on the tensile side and applying loads at an angle of 30° from the tooth axis. Superior static fracture resistance was observed when the wall remaining on the tooth had a height and thickness greater than 1.0 mm. The dynamic fatigue test showed high loading capacity or fracture resistance in specimens with large height and thickness. The dynamic fatigue test showed the influence of the remaining tooth structure on fracture resistance clearly. In conclusion, the static and dynamic fracture resistances increased with the height and thickness of the one wall remaining tooth structure.

Patient with Poor Esthetic Anterior Tooth Position Treated with Lithium Disilicate Mesial Cantilever Single-retainer Fixed Partial Denture: A Case Report.

We report a case of fixed prosthetic treatment for poor esthetics due to the position of the maxillary left lateral incisor in a 43-year-old woman. Initial examination revealed no carious lesions, but the tooth axis of the maxillary right canine showed mesial inclination of approximately 15°. Orthodontic treatment was first proposed but was declined by the patient as they did not wish to undergo a prolonged period of therapy. Therefore, recovery by extraction of the maxillary right lateral incisor and prosthetic treatment was proposed as an alternative. The method to be used for application of a 3-unit fixed partial denture and implant treatment was explained to the patient. She refused to give consent to this plan as well, however, due to concerns regarding the need to cut a lot from a non-problematic tooth and the length of time such treatment would require. Therefore, the problem was finally treated by application of a cantilever single-retainer fixed partial denture while giving sufficient consideration to extraction and occlusal contact. Lithium disilicate was used for the material of the prothesis. At 1 year after completion of treatment, no problem was observed with either the prosthetic appliance or the abutment teeth.