Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer.

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.

Conservative Treatment Using Platelet-Rich Plasma for Acute Anterior Cruciate Ligament Injuries in Highly Active Patients: A Retrospective Survey.

Background The recommended treatment for anterior cruciate ligament (ACL) injuries in active, sports-oriented patients is reconstructive surgery in order to regain stability and prevent secondary meniscal injuries. However, ACL reconstruction requires a long recovery period and poses issues such as decreased muscle strength due to tendon harvesting and postoperative osteoarthritis (OA) progression, thereby raising significant expectations for the advancement of conservative treatments. Recent studies have shown that platelet-rich plasma (PRP) therapy, which utilizes the tissue repair-promoting property of platelets, is effective for ACL injuries. Methods We administered PRP therapy within six weeks after ACL injury in patients who expressed the desire for an early return to sports through conservative care. After the treatment, patients wore a simple brace that limited deep flexion but placed no restrictions on weight bearing. Four months was the standard goal established for returning to pre-injury condition, and, depending on the target level, timing, and knee condition, we adjusted the additional PRP treatments and rehabilitation approach, gradually authorizing the patients' return to sport. We assessed the ligament repair status by magnetic resonance imaging (MRI) just before the full return to sports. A retrospective survey was conducted to evaluate the status of ligament repair and the condition of return-to-sport in patients with ACL injuries who underwent conservative treatment using PRP. Results The average patient age was 32.7 years and the average treatment was 2.8 PRP sessions. MRI evaluations confirmed that ligament continuity was regained in all cases. All the patients returned to their pre-injury level (Tegner Activity Scale 7.0) in an average of 139.5 days, but there was one instance of re-rupture following the return to sports. Conclusion All patients with ACL injury who underwent PRP therapy regained ligament continuity and returned to sport successfully with only one case of re-rupture.

KMT2A-rearranged sarcoma with unusual fusion gene CBX6::KMT2A::PYGO1.

Recently, rare sarcomas harboring KMT2A rearrangements have been reported. They occur in relatively young individuals, exhibit a sclerosing epithelioid fibrosarcoma-like morphology, and often have an aggressive prognosis. YAP1::KMT2A::YAP1 is the most common fusion gene, followed by VIM::KMT2A. We report the case of a 47-year-old man with a spindle cell tumor arising from the subcutaneous tissue of the right anterior chest. The tumor harbored an unusual novel fusion gene, CBX6::KMT2A::PYGO1. Histologically, the tumor consisted of proliferating spindle-shaped cells with uniform nuclei, which varied in cell density and the amount of intervening collagen fibers. After 2 years and 8 months without postoperative treatment, the patient showed no recurrence or metastasis. Although highly likely irreproducible, tumors with the CBX6::KMT2A::PYGO1 fusion gene were morphologically somewhat different from those containing the YAP1::KMT2A::YAP1. This suggests that KMT2A rearrangements with fusion gene partners different from YAP1 result in purely spindle-shaped cell tumors that produce collagen fibers.

Higher fibular head is a risk for lateral hinge fracture in medial open wedge high tibial osteotomy.

PURPOSE: To examine the association between the hinge position, fibular head position, and type III lateral hinge fracture (LHF) in patients with knee osteoarthritis (OA) who underwent medial open wedge high tibial osteotomy (MOWHTO). METHODS: This retrospective study examined patients who underwent MOWHTO. Radiographically, the Kellgren-Lawrence (K/L) classification, distance between the articular surface and the tip of the fibular head (fibular head position), hinge point (hinge position), type of LHF, and safe zone (within the proximal tibiofibular joint) outlier were evaluated. To determine the cut-off value of the hinge position and fibular head position associated with type III LHF, a receiver operating characteristic (ROC) curve analysis was performed. The odds ratio (OR) was calculated from the obtained cut-off values using logistic regression, which was adjusted by age, gender, body mass index, and opening distance. RESULTS: Among 132 knees in 120 patients, the radiographic severity of knee OA was 19 (14%), 73 (55%), and 40 (30%) of K/L grades 2, 3, and 4, respectively. LHF was observed in 40 knees (30%), including types I, II, and III fractures in 21 (16%), 5 (4%), and 14 (11%) knees, respectively. Hinge and fibular head positions were 16 and 10 mm, respectively, with significant correlation. Safe zone outlier was observed in 38 knees (29%). The hinge and fibular head positions with type III LHF were significantly higher (more cranial) than those with no fracture or other LHF subtypes. The ROC curve revealed that the cut-off value for the hinge and fibular head positions was 13.3 and 8.6 mm, respectively. The OR of the hinge and fibular head positions was 22.42 and 13.86, respectively. CONCLUSIONS: A higher hinge position was a risk factor for type III LHF and was associated with a higher fibular head in patients with knee OA who underwent MOWHTO. The hinge position should be placed at a certain distance from the articular surface to avoid type III LHF, especially in participants with higher fibular head position, even if the hinge position is located in the safe zone. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Genetic characterization of a novel organoid from human malignant giant-cell tumor.

Malignant giant-cell tumors are extremely rare bone sarcomas that transform from conventional giant-cell tumors during long periods of treatment. Owing to their rarity, no further analysis of their molecular pathogenesis exists, and thus, no standard treatment has been established. Recently, organoid culture methods have been highlighted for recapturing the tumor microenvironment, and we have applied the culture methods and succeeded in establishing patient-derived organoids (PDO) of rare sarcomas. This study aimed to investigate the genomic characteristics of our established novel organoids from human malignant giant-cell tumors. At our institute, we treated a patient with malignant giant-cell tumor. The remaining sarcoma specimens after surgical resection were cultured according to the air-liquid interface organoid-culture method. Organoids were xenografted into NOD-scid IL2Rgnull mice. The developed tumors were histologically and genomically analyzed to compare their characteristics with those of the original tumors. Genetic changes over time throughout treatment were analyzed, and the genomic status of the established organoid was confirmed. Organoids from malignant giant-cell tumors could be serially maintained using air-liquid interface organoid-culture methods. The tumors developed in xenografted NOD-scid IL2Rgnull mice. After several repetitions of the process, a patient-derived organoid line from the malignant giant-cell tumor was established. Immunohistochemical analyses and next-generation sequencing revealed that the established organoids lacked the H3-3A G34W mutation. The xenografted organoids of the malignant giant-cell tumor had phenotypes histologically and genetically similar to those of the original tumor. The established organoids were confirmed to be derived from human malignant giant-cell tumors. In summary, the present study demonstrated a novel organoid model of a malignant giant-cell tumor that was genetically confirmed to be a malignant transformed tumor. Our organoid model could be used to elucidate the molecular pathogenesis of a malignant giant-cell tumor and develop novel treatment modalities.

Chronologic Changes in the Elastic Modulus of a Healing Achilles Tendon Rupture Measured Using Shear Wave Elastography.

BACKGROUND: Shear wave elastography (SWE) has been used to examine the elasticity of a ruptured Achilles tendon; however, the healing process of a ruptured tendon has not been studied yet. This study aimed to detail the change in mechanical properties of a healing Achilles tendon rupture managed conservatively or surgically using SWE. METHODS: Using a prospective cohort study design, we evaluated the patients treated conservatively (conservative group) and surgically (surgical group) with the "gift-box" technique for an isolated index acute Achilles tendon rupture during their healing process. SWE measurements were taken of both the injured and uninjured sides every 4 weeks up to 24, 36, and 48 weeks after treatment. Additionally, tendon thickness and power Doppler (PD) grade were measured at the same time points as SWE measurements. The American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot rating system score and Achilles tendon Total Rupture Score (ATRS) were compared at 24 and 48 weeks. RESULTS: The ruptured Achilles tendon obtained an SWE value comparable with the unruptured side at 12 weeks in the conservative group and at 4 weeks with surgical group. The surgical group had significantly higher SWE values up to 24 weeks compared with the conservative group. Additionally, this group had a significantly larger increase in tendon thickness in nearly all periods. Both treatment groups were comparable regarding the PD grade, AOFAS score, and ATRS. CONCLUSION: SWE is a convenient noninvasive method to determine the progress of the healing process after tendon injury. Our analysis using SWE has revealed the detailed chronologic changes in SWE values and related mechanical properties of a healing Achilles tendon rupture, which can be used for devising appropriate rehabilitation protocols. LEVEL OF EVIDENCE: Level II, prospective cohort study.

Poor Accuracy of Intraoperation Medial Proximal Tibial Angle Measurement Compared to Alignment Rod Methods in Open-Wedge High Tibial Osteotomy for Medial Knee Osteoarthritis.

The alignment rod is widely used as an index for intraoperative alignment but alignment error is inevitable. The purpose of this study was to verify the accuracy of lower limb alignment correction by measurement of mechanical medial proximal tibial angle (MPTA) as an index in open-wedge high tibial osteotomy (OWHTO). This study was retrospective case series. This study involved 152 patients undergoing OWHTO for primary medial osteoarthritis. Alignment rod or MPTA measurement board was used as an index of optimal correction in OWHTO. Alignment rod was used from October 2013 to May 2017, and MPTA measurement board was used from June 2017 to April 2020. The correction using an alignment rod was that the weight-bearing line ratio (WBLR) passed through 62.5% of the tibial plateau which was defined as Fujisawa's point under intraoperative fluoroscopy (A rod group). The correction using MPTA measurement board was aligning the intraoperative MPTA to the preplanned angle (MPTA group). Preplanned optimal alignment was defined as Fujisawa's point in all patients. Knee injury and osteoarthritis outcome measure (KOOS), Knee Society scoring system objective knee score (KSS), 3-m timed up-and-go test (TUG), single-limb standing test (SLS), and isometric muscle strength of quadriceps and hamstrings were assessed as clinical results. WBLR, MPTA, joint-line convergence angle (JLCA), and joint-line obliquity (JLO) were assessed as radiological results preoperatively and at 1 year after surgery. The clinical and radiological results after OWHTO were compared with both groups. Postoperative WBLR in A rod group was closer to the target alignment (Fujisawa's point: 62.5) than in the MPTA group at all stage (A rod group vs. MPTA group: 63.1 vs. 54.6 at 6 months; 62.0 vs. 53.4 at 1 year; p < 0.001). There were no significant differences in the clinical results between both groups. The intraoperative measurement of medial proximal tibial angle has a risk of undercorrection after OWHTO. His study is a retrospective case series and reflects level of evidence IV.

Establishment of preanalytical conditions for microRNA profile analysis of clinical plasma samples.

The relationship between the expression of microRNAs (miRNAs) in blood and a variety of diseases has been investigated. MiRNA-based liquid biopsy has attracted much attention, and cancer-specific miRNAs have been reported. However, the results of analyses of the expression of these miRNAs vary among studies. The reproduction of results regarding miRNA expression levels could be difficult if there are differences in the data acquisition process. Previous studies have shown that the anticoagulant type used during plasma preparation and sample storage conditions could contribute to differences in measured miRNA levels. Thus, the impact of these preanalytical conditions on comprehensive miRNA expression profiles was examined. First, the miRNA expression profiles of samples obtained from healthy volunteers were analyzed using next-generation sequencing. Based on an analysis of the library concentration, human genome identification rate, ratio of unique sequences and expression profiles, the optimal preanalytical conditions for obtaining highly reproducible miRNA expression profiles were established. The optimal preanalytical conditions were as follows: ethylenediaminetetraacetic acid (EDTA) as the anticoagulant, whole-blood storage at room temperature within 6 hours, and plasma storage at 4°C or -20°C within 30 days. Next, plasma samples were collected from 60 cancer patients (3 facilities × 20 patients/facility), and miRNA expression profiles were analyzed. There were no significant differences in measurements except in the expression of erythrocyte-derived hsa-miR-451a. However, the variation in hsa-miR-451a levels was smaller among facilities than among individuals. This finding suggests that samples obtained from the same facility could show significantly different degrees of hemolysis across individuals. We found that the standardization of anticoagulant use and storage conditions contributed to reducing the variation in sample quality across facilities. The findings from this study could be useful in developing protocols for collecting samples from multiple facilities for cancer screening tests.

Study protocol for a randomised placebo controlled trial of platelet-rich plasma injection to prevent post-traumatic knee osteoarthritis after anterior cruciate ligament reconstruction.

INTRODUCTION: The elevated cytokine levels in patients suffering from anterior cruciate ligament (ACL) rupture may lead to acute post-traumatic arthritis (APTA) and post-traumatic osteoarthritis (PTOA). Due to its chondrogenerative and anti-inflammatory effect, platelet-rich plasma (PRP) therapy is expected to show a positive outcome in APTA and PTOA. The proposed trial aims to quantitatively measure the efficacy of PRP injection in arresting post-traumatic cartilage degeneration among patients after ACL reconstruction. METHODS AND ANALYSIS: This will be a single-blind, randomised, prospective, controlled clinical trial designed following the Consolidated Standards of Reporting Trials guidelines. After ACL reconstruction, 80 patients will be randomised to receive either leucocyte-poor PRP injection after joint aspiration or a placebo control group receiving only joint aspiration. Participants (age 20-49 years) will be those who have undergone ACL reconstruction within the past 2 weeks with a body mass index<35 and Kellgren Lawrence osteoarthritis grade<2. The primary outcome will include MRI-T2 values of knee cartilage at 6 months. The secondary outcomes will include pain assessment by Visual Analogue Scale, Knee injury and Osteoarthritis Outcome Score, blood and urine test, physical findings, measurements for muscle strength and joint stability. ETHICS AND DISSEMINATION: The study was approved by The Independent Ethics Committee for Clinical Trials of the Japanese Association for the Promotion of State-of-the-Art Medicine. Results of the trial and each of the outcomes will be shared via conferences and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTb030200391.

Establishment of Organoids From Human Epithelioid Sarcoma With the Air-Liquid Interface Organoid Cultures.

Background: Although biological resources are essential for basic and preclinical research in the oncological field, those of sarcoma are not sufficient for rapid development of the treatment. So far, some sarcoma cell lines have been established, however, the success rate was low and the established sarcoma types were frequently biased. Therefore, an efficient culture method is needed to determine the various types of sarcomas. Organoid culture is a 3-dimentional culture method that enables the recapitulation of the tumor microenvironment and the success rate reported is higher than the 2-dimentional culture. The purpose of this study was to report our newly established organoids from human epithelioid sarcoma using the air-liquid interface organoid culture method. Methods: We treated 2 patients with epithelioid sarcoma in our institute. The remaining sarcoma specimens after surgical resection were embedded in collagen type 1 gels according to the air-liquid interface organoid culture method. After serial passages, we xenografted the organoids to NOD-scid IL2Rgnull (NSG) mice. Using the developed tumors, we performed histological and genomic analyses to compare the similarities and differences with the original epithelioid sarcoma from the patient. Results: Organoids from the epithelioid sarcoma could be serially cultured and maintained in collagen type 1 gels for more than 3 passages. Developed orthotopic tumor xenografts were detected in the NSG mice. After the process was repeated severally, the patient derived organoid lines from the epithelioid sarcoma were established. The established organoids showed loss of integrase interactor 1 expression with polymerase chain reaction and immunohistochemical analyses. The xenografted organoids of the epithelioid sarcoma had histologically similar phenotypes with the original tumor and genetically resembled it to some degree. Conclusions: The present study demonstrated 2 novel established organoid models of epithelioid sarcoma, and our organoid models could be used to investigate the molecular pathogenesis and develop a novel treatment.

Association of Recurrent Tear After Arthroscopic Rotator Cuff Repair and Superoxide-Induced Oxidative Stress.

BACKGROUND: Recurrent tears after arthroscopic rotator cuff repair (ARCR) remain a significant clinical problem. Oxidative stress contributes to the degeneration of the rotator cuff, and a degenerative rotator cuff can lead to recurrent tear after ARCR. However, the correlation between oxidative stress and retear after ARCR is unclear. PURPOSE: To investigate the correlation between superoxide-induced oxidative stress and recurrent tear after ARCR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total of 68 patients who underwent ARCR using a suture-bridge technique participated in this study. Specimens were collected from the edge of the torn tendon during surgery. The modified Bonar score was used to evaluate degeneration of the rotator cuff on histological specimens, and fluorescence intensity on dihydroethidium (DHE) staining was used to detect oxidative stress. Superoxide dismutase (SOD) enzyme activity was also measured. The following were used for clinical evaluation: age, tear size on magnetic resonance imaging (MRI) before surgery, Goutallier classification on MRI before surgery, and Japanese Orthopaedic Association score before and 6 months after surgery. After the repaired rotator cuffs were evaluated on MRI 6 months after surgery, the patients were divided into groups: those with a healed rotator cuff (healed group; n = 46) and those with a recurrent tear (retear group; n = 22). The significant differences between the groups were determined with regard to clinical evaluation, modified Bonar score, DHE intensity, and SOD activity. In addition, multivariate logistic regression analysis was performed to investigate risk factors for recurrent tear. RESULTS: Age, tear size, Goutallier classification, modified Bonar score, DHE intensity, and SOD activity were significantly greater in the retear group than in the healed group, although the Japanese Orthopaedic Association score was not significantly different. Multiple logistic regression analysis demonstrated that age, tear size, and SOD activity were significantly correlated with recurrent tear. CONCLUSION: In addition to tear size and age, superoxide-induced oxidative stress may be an exacerbating factor for retear after ARCR.

Effect of 10-Methacryloyloxydecyl Dihydrogen Phosphate Concentrations in Primers on Bonding Resin Cements to Zirconia.

PURPOSE: To investigate the effect of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) concentration in primers on bonding of resin cements to zirconia. MATERIALS AND METHODS: Highly translucent partially stabilized zirconia plates were bonded to stainless steel rods using one of 3 commercially available resin cements without adhesive functional monomers and without air-abrasion. Ten specimens of each resin cement group were pretreated with one of the primers containing 0.5, 1.0, 2.0, 3.0, 4.0, or 5.0 wt% of MDP dissolved in ethanol, or one of 3 commercial ceramic primers containing MDP and silane coupling agents. Untreated specimens were used as controls. The tensile bond strength was measured after 24 hours (TC0) and after thermal cycling at 4 to 60°C (TC3,500). Data were statistically analyzed using 1- or 2-way ANOVA and Tukey-Kramer post-hoc tests (α = 0.05). RESULTS: The mean tensile bond strength in the unpretreated group was significantly lower compared to that in the pretreated groups with MDP-containing primers regardless of the resin cement used (p < 0.0001). The tensile bond strengths increased with an increase in MDP concentration from 0.5 wt% to 3.0 wt% or 4.0 wt%. Pretreated groups with 4.0-wt% MDP-containing primer showed significantly higher tensile bond strengths than pretreated groups with commercial ceramic primers regardless of the resin cement used and thermal cycling (p < 0.0001). CONCLUSION: Primers containing 4.0-wt% MDP achieved higher bond strengths of resin cements to zirconia compared to commercial ceramic primers containing MDP and silane coupling agent.

Suppression of Non-Random Fertilization by MHC Class I Antigens.

Hermaphroditic invertebrates and plants have a self-recognition system on the cell surface of sperm and eggs, which prevents their self-fusion and enhances non-self-fusion, thereby contributing to genetic variation. However, the system of sperm-egg recognition in mammals is under debate. To address this issue, we explored the role of major histocompatibility complex class I (MHC class I, also known as histocompatibility 2-Kb or H2-Kb and H2-Db in mice) antigens by analyzing H2-Kb-/-H2-Db-/-ß2-microglobulin (ß2M)-/- triple-knockout (T-KO) male mice with full fertility. T-KO sperm exhibited an increased sperm number in the perivitelline space of wild-type (WT) eggs in vitro. Moreover, T-KO sperm showed multiple fusion with zona pellucida (ZP)-free WT eggs, implying that the ability of polyspermy block for sperm from T-KO males was weakened in WT eggs. When T-KO male mice were intercrossed with WT female mice, the percentage of females in progeny increased. We speculate that WT eggs prefer fusion with T-KO sperm, more specifically X-chromosome-bearing sperm (X sperm), suggesting the presence of preferential (non-random) fertilization in mammals, including humans.

Influence of alumina air-abrasion for highly translucent partially stabilized zirconia on flexural strength, surface properties, and bond strength of resin cement.

OBJECTIVE: This study aims to evaluate the influence of different air-abrasion pressures and subsequent heat treatment on the flexural strength, surface roughness, and crystallographic phases of highly translucent partially stabilized zirconia (Y-PSZ), and on the tensile bond strength of resin cement to Y-PSZ. METHODOLOGY: Fully sintered zirconia specimens were ground with SiC paper (control) and/or air-abraded with 50 µm particles of alumina at 0.1, 0.15, 0.2, or 0.3 MPa or left as-sintered. After air-abrasion at 0.2 MPa (0.2AB), additional specimens were then heated to 1500°C, and held for one hour at this temperature (0.2AB+HT1h). Flexural strength and surface roughness were evaluated. Crystalline phase identification was also carried out using X-ray diffraction. Bonded zirconia specimens with self-adhesive resin cement were stored in distilled water at 37°C for 24 h, either with or without aging (thermal cycling 4-60°C/20000). Results were analyzed statistically by ANOVA and Tukey-Kramer tests. RESULTS: The flexural strength decreased with the increase in air-abrasion pressure, while in contrast, the surface roughness increased. The lowest flexural strength and the highest roughness value were found for the 0.2AB and 0.3AB groups, respectively. All groups contained cubic-, tetragonal ( t )-, and rhombohedral ( r )-ZrO2 phases with the exception of the as-sintered group. Upon increasing the air-abrasion pressure, the relative amount of the r -ZrO2 phase increased, with a significant amount of r -ZrO2 phase being detected for the 0.2AB and 0.3AB groups. The 0.2AB+HT1h group exhibited a similar flexural strength and t -ZrO2 phase content as the as-sintered group. However, the 0.2AB group showed a significantly higher tensile bond strength (p<0.05) than the 0.2AB+HT1h group before and after aging. CONCLUSION: Micromechanical retention by alumina air-abrasion at 0.2 MPa, in combination with chemical bonding of a resin to highly translucent Y-PSZ using a MDP-containing resin cement may enable durable bonding.

Increased Stiffness of Rotator Cuff Tendons in Frozen Shoulder on Shear Wave Elastography.

OBJECTIVES: To evaluate the stiffness and morphologic characteristics of the capsule, rotator cuff tendons and muscles, coracohumeral ligament (CHL), and long head of the biceps in patients with frozen shoulder using shear wave elastography (SWE) with B-mode ultrasound. METHODS: Thirty-two patients with frozen shoulder were divided into freezing and frozen phases. All patients had limitations of their range of motion without rotator cuff tears. Stiffness was measured by SWE in the supraspinatus (SSp) tendon, infraspinatus (ISp) tendon, SSp muscle, ISp muscle, teres minor muscle, upper and lower trapezius muscles, posterior capsule, CHL, and long head of the biceps. The posterior capsule and CHL thicknesses were also investigated with B-mode ultrasound. All values were compared in the affected and unaffected shoulders in each phase. RESULTS: The SWE values for the SSp and ISp tendons in the freezing phase and the CHL in the frozen phase were significantly greater on the affected side than the unaffected side (mean ± SD, 280.4 ± 125.3 versus 178.1 ± 73.3, 318.4 ± 110.7 versus 240.8 ± 91.5, and 287.2 ± 135.3 versus 214.1 ± 91.1 kPa, respectively; P < .05). The posterior capsule in both the freezing and frozen phases and the CHL in the frozen phase were significantly thicker on the affected side than the unaffected side (1.3 ± 0.2 versus 0.9 ± 0.3, 1.2 ± 0.4 versus 0.9 ± 0.3, and 4.4 ± 1.4 versus 3.3 ± 1.1 mm; P < .01). CONCLUSIONS: The SWE values of the both SSp and ISp tendons increased in the freezing phase, and that of the CHL also increased in the frozen phase. Not only the change in thickness of the capsule but also the change in stiffness of the rotator cuff may correlate with frozen shoulder.

Association of Superoxide-Induced Oxidative Stress With Rotator Cuff Tears in Human Patients.

Rotator cuff degeneration is one of the factors contributing to rotator cuff tears. Oxidative stress is involved in tendon degeneration, and superoxide-induced oxidative stress plays a pathological role in regulating the balance between oxidation and reduction. The role of oxidative stress in rotator cuff tears, however, is unclear. This study, therefore, aimed to investigate the contribution of superoxide-induced oxidative stress to rotator cuff tears. Seventy patients were recruited and divided into two groups: patients with (Ruptured group) and those without (Unruptured group) a rotator cuff tear. Specimens from both groups were collected during surgery. Degeneration morphology was classified according to the degeneration score. Superoxide-induced oxidative stress was assessed according to dihydroethidium (DHE) relative fluorescence intensity, capacity for antioxidation according to superoxide dismutase (SOD) activity, and the balance between oxidation and reduction based on the redox ratio. Data were compared between groups. Correlations between the degeneration score and the oxidative stress factors were calculated. Degeneration score and DHE relative fluorescence intensity were significantly higher in the Ruptured than the Unruptured group. The SOD activity was not significantly different between groups. Degeneration score was positively correlated with both DHE relative fluorescence intensity and SOD activity. Thus, superoxide-induced oxidative stress and tendon degeneration were greater in rotator cuff tear tissues than in those with no tear, suggesting that oxidative imbalance may be involved in degenerative rotator cuff tears. Clinical Relevance: Understanding the mechanisms of superoxide-induced oxidative stress may lead to targeted tissue therapy for degenerative rotator cuff tears. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:212-218, 2020.

Bonding to industrial indirect composite blocks: A systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the effect of surface conditioning methods on the bond strength of industrial indirect composite blocks (ICs). METHODS: Based on the PICOS strategy, the Medline via PubMed, Embase and Web of Science (ISI - Web of Knowledge) electronic databases were searched for peer-reviewed articles in both English and Chinese, with no publication year limit. In vitro studies evaluating the effects of surface conditioning on the bond strength of ICs were selected. The meta-analysis was conducted to calculate the mean difference between surface-conditioned ICs and unconditioned controls. Subgroup analysis was performed to evaluate the different surface conditioning methods, separately for polymer-infiltrated ceramic network (PICN) material and the ICs with dispersed fillers (ICDFs). Meta-analyses were performed with a random-effects model at a significance level of 0.05. RESULTS AND SIGNIFICANCE: From 802 relevant studies, 25 were selected for full-text analysis. Nineteen studies were eligible for inclusion in this systematic review, whereas 9 studies were included in the meta-analysis. A manual search of the principal periodicals specific to the area resulted in no additional articles. The meta-analysis indicated a significant difference in bond strength between the surface-conditioned ICs and controls under both non-aged and aged conditions. The combination of mechanical and chemical conditioning yielded the highest bond strength of ICs. This meta-analysis suggests that chemical etching followed by a universal primer and alumina air abrasion followed by a silane coupling agent could be considered the best strategy for optimizing the bond strength of PICN materials and ICDFs under aged conditions, respectively.

Influence of cleaning methods on the bond strength of resin cement to saliva-contaminated lithium disilicate ceramic.

OBJECTIVES: The aim of the present study was to examine the influence of different cleaning methods on the bond strength of resin cement to saliva-contaminated lithium disilicate ceramic. MATERIALS AND METHODS: Lithium disilicate ceramic specimens (n = 8/group) were etched with 5% hydrofluoric acid (HF) to comprise the control group. After or before saliva contamination, specimens were cleaned with one of five methods: rinsing with water-spray (WS), K etchant GEL (PA), Ivoclean (IC), AD Gel (ADG), or application of a silane coupling agent before immersion in saliva (SCA). Stainless steel rods were bonded to the ceramic with resin cement. The tensile bond strength was measured after 24 h (TC0) and after thermal cycling at 4-60 °C (TC20000). Specimen surfaces were also evaluated using X-ray photoelectron spectroscopy. Data were statistically analyzed using two-way ANOVA and Tukey tests (α = 0.05). RESULTS: Both the cleaning method (p = 0.0001) and storage condition (p = 0.0001) significantly affected the bond strength results. Before or after TCs, no significant differences in bond strength were observed between the control group and the other cleaning groups except for the WS group, which had a significantly lower bond strength than did the PA, IC, ADG, or SCA groups (p < 0.05). The level of nitrogen in the ADG group was almost equal to that in the control group. CONCLUSIONS: WS cleaning did not restore the bond strength of resin cement to saliva-contaminated lithium disilicate ceramic etched with HF, while PA, IC, ADG, and SCA all benefited. CLINICAL RELEVANCE: Lithium disilicate ceramic restorations etched with HF should to be cleaned with ADG after saliva contamination.

Influence of alumina air-abrasion for highly translucent partially stabilized zirconia on flexural strength, surface properties, and bond strength of resin cement

Abstract Objective This study aims to evaluate the influence of different air-abrasion pressures and subsequent heat treatment on the flexural strength, surface roughness, and crystallographic phases of highly translucent partially stabilized zirconia (Y-PSZ), and on the tensile bond strength of resin cement to Y-PSZ. Methodology Fully sintered zirconia specimens were ground with SiC paper (control) and/or air-abraded with 50 µm particles of alumina at 0.1, 0.15, 0.2, or 0.3 MPa or left as-sintered. After air-abrasion at 0.2 MPa (0.2AB), additional specimens were then heated to 1500°C, and held for one hour at this temperature (0.2AB+HT1h). Flexural strength and surface roughness were evaluated. Crystalline phase identification was also carried out using X-ray diffraction. Bonded zirconia specimens with self-adhesive resin cement were stored in distilled water at 37°C for 24 h, either with or without aging (thermal cycling 4-60°C/20000). Results were analyzed statistically by ANOVA and Tukey-Kramer tests. Results The flexural strength decreased with the increase in air-abrasion pressure, while in contrast, the surface roughness increased. The lowest flexural strength and the highest roughness value were found for the 0.2AB and 0.3AB groups, respectively. All groups contained cubic-, tetragonal ( t )-, and rhombohedral ( r )-ZrO2 phases with the exception of the as-sintered group. Upon increasing the air-abrasion pressure, the relative amount of the r -ZrO2 phase increased, with a significant amount of r -ZrO2 phase being detected for the 0.2AB and 0.3AB groups. The 0.2AB+HT1h group exhibited a similar flexural strength and t -ZrO2 phase content as the as-sintered group. However, the 0.2AB group showed a significantly higher tensile bond strength (p<0.05) than the 0.2AB+HT1h group before and after aging. Conclusion Micromechanical retention by alumina air-abrasion at 0.2 MPa, in combination with chemical bonding of a resin to highly translucent Y-PSZ using a MDP-containing resin cement may enable durable bonding.

Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice.

Outer dense fibre 2 (Odf2 or ODF2) is a cytoskeletal protein required for flagella (tail)-beating and stability to transport sperm cells from testes to the eggs. There are infertile males, including human patients, who have a high percentage of decapitated and decaudated spermatozoa (DDS), whose semen contains abnormal spermatozoa with tailless heads and headless tails due to head-neck separation. DDS is untreatable in reproductive medicine. We report for the first time a new type of Odf2-DDS in heterozygous mutant Odf2+/- mice. Odf2+/- males were infertile due to haploinsufficiency caused by heterozygous deletion of the Odf2 gene, encoding the Odf2 proteins. Odf2 haploinsufficiency induced sperm neck-midpiece separation, a new type of head-tail separation, leading to the generation of headneck sperm cells or headnecks composed of heads with necks and neckless tails composed of only the main parts of tails. The headnecks were immotile but alive and capable of producing offspring by intracytoplasmic headneck sperm injection (ICSI). The neckless tails were motile and could induce capacitation but had no significant forward motility. Further studies are necessary to show that ICSI in humans, using headneck sperm cells, is viable and could be an alternative for infertile patients suffering from Odf2-DDS.