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Notch signaling contributes to tissue development and homeostasis, but little is known about its role in morular differentiation of endometrial carcinoma (Em Ca) cells. The current study focused on crosstalk between Notch and β-catenin signaling in Em Ca with morules. Promoters of hairy and enhancer of split 1 (Hes1) and mastermind-like 2 (MAML2) were activated by Notch intracellular domain 1 but not β-catenin, and a positive feedback loop between Hes1 and MAML2 was observed. Immunoreactivities for nuclear β-catenin, Hes1, and MAML2, as well as the interaction between β-catenin and Hes1 or MAML2, were significantly higher in morular lesions compared with surrounding carcinoma in Em Ca. Inhibition of glycogen synthase kinase-3β (GSK-3β) increased expression of total nuclear and cytoplasmic GSK-3β and its phosphorylated forms, as well as Notch intracellular domain 1, Hes1, and active β-catenin. GSK-3β inhibition also decreased proliferation and migration, consistent with the response of cells stably overexpressing Hes1. Finally, the nuclear/cytoplasmic GSK-3β score was significantly higher in morules compared with surrounding carcinoma in Em Ca, and it was positively correlated with nuclear β-catenin, Hes1, and MAML2 scores. This complex interplay between Notch effectors and β-catenin signaling through GSK-3β inhibition contributes to the establishment and maintenance of β-catenin–mediated morular differentiation, which is, in turn, associated with reduced proliferation and inhibition of migration in Em Ca.

Epithelial-mesenchymal transition is a hallmark of uterine carcinosarcoma (UCS). Here, shotgun proteomics analysis used to identify biomarkers associated with blebbistatin-mediated epithelial-mesenchymal transition in UCS indicated up-regulation of nucleobindin-2 (NUCB2) in endometrial carcinoma (Em Ca) cells. Expression of N-cadherin, Snail, Slug, and ZEB1 was reduced in NUCB2 knockout Em Ca cells, whereas ZEB1, Twist1, and vimentin were up-regulated in NUCB2-overexpressing Em Ca cells. NUCB2 knockout reduced cell proliferation and migration, whereas NUCB2 overexpression had the opposite effect. Treatment of Em Ca cells with transforming growth factor (TGF)-β1 dramatically altered morphology toward a fibroblastic appearance; concomitantly, expression of NUCB2 and ZEB1 increased. The NUCB2promoter was also activated by transfection of Smad2. In UCS tissues, NUCB2 expression was significantly higher in sarcomatous compared with carcinomatous components, which was consistent with increased TGF-β1 mRNA expression in stromal and sarcomatous components compared with carcinomatous components. In addition, NUCB2 score correlated positively with ZEB1 and vimentin scores, whereas ZEB1 score correlated positively with Slug and vimentin scores and inversely with the E-cadherin score. Collectively, these data indicate that TGF-β–dependent up-regulation of NUCB2 and ZEB1 contributes to the phenotypic characteristics of sarcomatous components in UCS.

A 36-year-old White man with no relevant medical history was referred to our clinic for evaluation of progressive muscle weakness of both lower limbs. He reported difficulty climbing stairs and standing up from a chair progressing over the prior 2 years. He preferred to lead with his left leg when climbing stairs because of more significant weakness of the right leg. He denied upper extremity weakness, abnormal sensation, muscle cramping, contractures, myalgias, change of urine color, skin rash, dysphagia, dysarthria, dyspnea, or exposure to new medications or toxins. He denied a family history of similar conditions. Neurologic examination was remarkable for asymmetric lower extremity muscle weakness. Muscle atrophy was noted in right quadriceps femoris, hamstrings, and posterior calf (Figure 1). The Medical Research Council grade was 4/5 for bilateral hip flexion, abduction, and adduction. There was asymmetric weakness of knee extension (4-/5 right and 4/5 left), knee flexion (4-/5 right and 4+/5 left), and ankle plantar flexion (4/5 right and 5/5 left). Foot dorsiflexion was normal bilaterally. He had a mild Trendelenburg gait. He did not have scapular winging, scoliosis, or percussion or grip myotonia. The remainder of neurologic examination was normal, including deep tendon reflexes. Previous evaluation at an outside facility revealed elevated serum creatine kinase (CK) 4,283 unit/L. Prior electrodiagnostic testing including nerve conduction studies (NCS) and needle electromyography (EMG)–reported findings of myopathy. Muscle biopsy was subsequently performed in left quadriceps femoris and reportedly revealed rare inflammatory cells; additional details were not available for review. He had been taking prednisone (40 mg/d) for 8 months and oral methotrexate (15 mg/wk) for 2 months followed by azathioprine (50 mg/d) for 6 months, which did not improve his symptoms. An electrocardiogram (ECG) was normal.

With the increasing number of patients undergoing arthroscopic rotator cuff repair (ARCR), postoperative pain control in these patients has become an important issue. We investigated and compared post-operative pain relief with intravenous acetaminophen (IA) and interscalene brachial plexus block (IBPB) after ARCR.

Rotator cuff tears that have flipped upon itself and adhered medially have been recently described as Fosbury flop tears (FFT). However, there are no reports on the cause and clinical outcomes of FFT. We investigated the preoperative anatomical factors and clinical outcomes related to the occurrence of FFT.

The diagnosis of Barrett’s esophageal adenocarcinoma (BEA) in patients with Barrett’s esophagus (BE) using endoscopy can be difficult and there are few specific endoscopic findings for BEA. However, white globe appearance (WGA) has been reported to be a specific endoscopic finding for early gastric cancer. We encountered a 51-year-old male patient with BEA exhibiting WGA. Esophagogastroduodenoscopy identified a red, depressed lesion of 10 mm within the long-segment BE (LSBE), while magnifying endoscopy with narrow-band imaging identified WGA. Endoscopic submucosal dissection (ESD) was performed based on our suspicion of BEA. Based on the ESD findings, we diagnosed adenocarcinoma accompanying LSBE histopathologically. WGA was identified, and intraglandular necrotic debris was discovered histologically at the same site. Therefore, WGA may be helpful in the diagnosis of BEA.

We investigated clinical results of manipulation under ultrasound-guided cervical nerveroot block (MUC) in frozen shoulder (FS).

We evaluated the detection rate of Cutibacterium acnes(C. acnes) for patients who underwent arthroscopic Bankart repair for traumatic anterior shoulder instability.

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Rotator cuff tears are divided into complete and partial tears, and partial rotator cuff tears include articular-sided tears and bursal-sided tears. Tears are caused by extrinsic, intrinsic, or traumatic factors; however, the mechanisms by which partial tears occur remain unknown. Recent reports have described the correlation between acromial morphology and rotator cuff tears. To date, no reports have investigated acromial morphology in partial tears. The purpose of this study is to evaluate the incidence of abnormal acromial morphology in both partial articular-sided and bursal-sided rotator cuff tears.

Introduction: Manipulation under ultrasound-guided fifth and sixth cervical nerve root block (MUC) is a recognized form of treatment for patients with persistent frozen shoulder (FS). This study aimed to investigate the confirmatory hypothesis testing that the MUC has a significant clinical effect on FS refractory to conservative treatments and to assess its adverse events. Methods: This is a retrospective observational study on patients with FS treated in the past 8 years. Although 77 patients were eligible for this study, only 68 were enrolled. The patients were evaluated immediately before the MUC and at 1, 3, and 6 months after with the use of the Japanese Orthopaedic Association shoulder score. Simultaneously, ranges of motion of the affected shoulder were measured in two directions: forward flexion and external rotation. A paired ttest or a Wilcoxon signed-rank test was used to compare differences in outcomes between before and 6 months after MUC. We also assessed any adverse events during and after the MUC. Results: Regarding the primary outcome, confirmatory testing showed statistically significant improvements in every outcome value at 6 months after MUC (p< 0.001). In terms of adverse events, two patients (2.9%) had vasovagal reflex, one (1.5%) had a panic attack during the block procedure, and a 72-year-old female patient (1.2%) had an avulsion fracture of the inferior glenoid during the manipulation procedure, although all of them recovered spontaneously without any residual functional impairment. Conclusion: The results showed that significant clinical effects of the MUC on FS were observed through a confirmatory analysis with a sufficient sample size. However, several complications that could occur during the block and manipulation procedures should be considered.

Al-Mg alloy strips were fabricated by the vertical-type high-speed twin-roll casting. Periodic patterns on the strip surface were observed in the casting direction consisting of the shiny region and un-shiny region with cracks. The un-shiny region and cracks remain even after successive cold rolling. Therefore, formation of the periodic patterns during casting should be suppressed. In this study, the formation mechanism of the periodic patterns of the JIS-AC7A strips was examined by microstructural observation and compositional analysis. The cross-sectional observation in the un-shiny region revealed the inverse segregation of Mg and Fe from the mid-thickness area of the strip toward the surface along the grain boundaries. It is considered that the residual liquid is squeezed out from the mid-thickness area of the strip toward the surface through the grain boundaries, and results in the formation of the un-shiny region. Temperature measurement was performed at the gap formed between the roll surface and the nozzle tip by using thermocouples. The strips were also fabricated by using the nozzles with various tip shapes in order to change the contact conditions between the melt and roll surface. The oscillation of the molten metal meniscus in the gap between the roll surface and the nozzle tip is considered to be one of the possible reasons of the formation of the periodic patterns on the strip surface.

Objective The aim of this study was to evaluate an intraarticular injection of different doses of autologous mesenchymal stem cells (MSCs) for improving repair of midterm osteochondral defect.Design At 4 weeks postoperative marrow stimulation model bilaterally (3 mm diameter; 4 mm depth) in the medial femoral condyle, autologous MSCs were injected into knee joint. Twenty-four Japanese rabbits aged 6 months were divided randomly into 4 groups (n= 6 per group): the control group and and MSC groups including 0.125, 1.25, and 6.25 million MSCs. Repaired tissue was assessed macroscopically and histologically at 4 and 12 weeks after intraarticular injection of MSCs.Results At 12 weeks, there was no repair tissue in the control group. The gross appearance of the 1.25 and 6.25 million MSC groups revealed complete repair of the defect with white to pink tissue at 12 weeks. An osteochondral repair was histologically significantly better in the 1.25 and 6.25 million MSC groups than in the control and 0.125 million MSC groups at 4 and 12 weeks, due to presence of hyaline-like tissue in the deep layer at 4 weeks, and at 12 weeks hyaline cartilage formation at the periphery and fibrous tissue containing some chondrocytes in the deep layer of the center of the defect. Subchondral bone was restructured in the 1.25 and 6.25 million MSC groups, although it did not resemble the normal bone.Conclusion An intraarticular injection of 1.25 or 6.25 million MSCs could promote the repair of subchondral bone, even in the case of midterm osteochondral defect.

Spheroidization of Al grains is required for the production of semi-solid slurry by either a partial solidification route or partial melting route. In this research, Al–5.5at%Mg alloy with dendrite structure was plastically deformed with 33 % compression and partially melted in a semi-solid state in order to obtain globular solid grains. Color etching method by Weck’s reagent (distilled water 100 mL; KMnO44 g; NaOH 1 g) was used for microstructure observation. During microstructure evolution of compressed specimen, the deformed dendrite changed gradually to the spheroidal shape due to the partial melting at the semi-solid temperature range. In the optical micrograph of the etched specimen, the microstructure was revealed with different color and contrast. The original shape of the spheroidal Al grains at the semi-solid state could be visualized clearly in the quenched microstructure. The solid fractions were measured for the entire semi-solid temperature ranging from 585 to 625 °C. By eliminating the growth layer of Al grains formed during water quenching, the solid fractions were evaluated accurately.

This study aimed to investigate risk factors for recurrence of frozen shoulder after shoulder manipulation under ultrasound-guided cervical nerve root block (MUC).

Hereditary neuropathy with liability to pressure palsies (HNPP) is a rare autosomal-dominant disorder that most commonly produces recurrent painless focal sensory and motor neuropathies often preceded by minor, mechanical stress, or minor trauma. Herein, we report 2 pediatric cases of HNPP with atypical presentations; isolated muscle cramping and toe walking. Electrophysiologic testing disclosed multifocal sensorimotor polyneuropathy with slowing of sensory conduction velocities in both cases, which prompted PMP 22 gene deletion testing. Multifocal sensorimotor electrophysiologic abnormalities, with slowing of sensory conduction velocities should raise consideration of HNPP in childhood. These case reports emphasize that the diagnosis of HNPP in children requires a high index of suspicion.

Magnetic pulse welding (MPW) which is one of the impact welding methods is suitable for a wide variety of combinations of similar and dissimilar metals. The flyer plate is accelerated by electromagnetic force and collided to the parent plate. A characteristic wavy interface is formed. The impact velocity and impact angle of the flyer plate during impact are important parameters which affect the interface morphology. In the case of dissimilar metals (e.g. Al/Cu, Al/Fe), the intermediate layer (such as intermetallic compound (IMC)) is formed by wavy interface formation and local temperature increase. The intermediate layer often decreases the bonding strength. Wavy interface formation mechanism and temperature increase at the joint interface should be investigated in order to obtain the dissimilar metal joint with high bonding strength. In this study, the impact velocity and impact angle of the flyer plate were obtained by using ANSYS Emag-Mechanical. Based on the obtained impact velocity and impact angle of the flyer plate in the MPW, the wavy interface formation and temperature change were reproduced by using ANSYS Autodyn for solving non-liner dynamics problems. Al sheets and Cu sheets were joined by the MPW. The joint interface was observed by OM and SEM and compared to the simulation result.

A horizontal-type twin roll casting method has been popular for producing aluminum alloy strips, however, it is characterized by a relatively low productivity (1~6 m/min). In contrast, a vertical-type high-speed twin-roll casting method possesses an extremely high productivity (60~120 m/min (1~2 m/s)) and an excellent heat extraction ability. The rapid cooling effect provided significant microstructure refinement and mechanical properties improvement in various kinds of cast aluminum alloy products. Not only “product to product recycling” but also “up-grade recycling” can be achieved by making good use of these merits. Two examples of application showing the potential of vertical-type high-speed twin roll casting method are presented. (1) Several kinds of Al-Si base alloy were cast into the strips. Not only strength and toughness but also formability was increased in the twin roll cast products. In particular, great improvement in deformability shows the potential of the twin-roll cast aluminum alloy products as substitutes for some wrought aluminum alloy products. (2) The vertical-type tandem twin-roll caster was able to fabricate a clad strip by single step. The A4045/A3003/A4045 aluminum alloy clad sheets produced by the twin-roll casting showed better mechanical properties than the conventional hot-roll bonded clad sheets.

For decades, twin-roll casting has been applied for manufacturing aluminum alloy sheets. This conventional process contributes to make thin aluminum sheets from the molten metal directly. Recently, vertical-type high-speed twin-roll casting (HSTRC) has been developed with much higher casting speed rather than the horizontal-type. Some modifications such as feeding nozzle and water-cooling system of copper rolls contribute to increase cooling rates. This characteristic leads to many metallurgical advantages like grain refinement, super-saturation of alloying elements and fine distribution of secondary particles. The objective of this study is to investigate the constituent particles in HSTRC aluminum alloy. The commercial Al-Mn alloy strip was successfully fabricated by HSTRC. Clearly different microstructure was found in thickness direction. Many constituent particles observed along the grain boundaries/cell boundaries as well as inside of Al matrix on the surface area, while eutectic structure around globular grain boundaries was observed in mid-central area. The morphology as well as chemical compositions of the constituent particles were investigated.

The present work deals with the relationship between microstructure and mechanical properties of A356 aluminum alloy which was produced via thixocasting process under different casting conditions. Feedstock billets were heated to a target temperature to obtain a semi-solid slurry with the required solid fraction. Some billets were heated to a fully-melted condition. In order to obtain fine and spheroidized Al grains, some billets for the partially melting were compressed axially by 33% at a room temperature before heating. The completely-melted and partially-melted slurries were die-cast by using a die-cast machine, and hour glass-shaped rod-type tensile specimens and small-size plate-type tensile specimens were obtained. Small cubic specimens were also collected from the die-cast products for microstructural evaluation. They were polished, and etched by Weck’s reagent. The partially-melted specimen which was compressed before heating shows the spherical Al grains. But the grain of the strain-free partially-melted specimen exhibited complicated morphology. The fully-melted specimen shows the fine and dendrite structure.

The microstructural characteristics and formation mechanism of intermediate layers at the explosive welded Al/Fe wavy interface were investigated by experimental and numerical analyses. Two types of intermediate layers were obtained at the wavy joint interface produced at an impact velocity of 750m/s and an impact angle of 15°. The layer that was formed in the tail-side included the area showing a dendritic structure consisting of Al3Fe and Al5Fe2. This indicated that local melting occurred in the area. In contrast, the layer that was formed in the front-side showed no evidence of melting. The formation behavior and temperature change at the Al/Fe interface formed by an oblique collision were simulated by the smoothed particle hydrodynamics (SPH) method. The simulation results revealed that on the tail-side, a mixture of Al and Fe particles formed and a large local temperature increase exceeding the melting temperature of Fe and Al occurred. The front-side showed a small temperature increase. The composition ratio of Al and Fe, and the temperature distribution at the joint interface calculated by the SPH simulation provided plausible explanations for the formation of two types of intermediate layers in each position.

In solid-state stud welding, joining is completed within a few milliseconds by using a large discharge current and pressure. Materials with high electrical resistivity are candidates for producing higher Joule heat from the same electric discharge energy. In this study, the suitability of solid-state stud welding for joining steel studs to steel plates was examined. Steel studs were successfully joined to steel plates at charged voltages of 125–200V without distortion of the plate and tarnish marks on the back surface. The joint interface between the projection and plate was arc-shaped. The deformation behavior was notably different from that in previous reports of joining aluminum alloy studs to aluminum alloy plates or magnesium alloy plates. Observation of the joining area revealed that the projection and plate deformed and spread along the plate surface, squeezing the plate material. The projection and plate deformed more severely as the charged voltage increased. The original shape of the projection tip was partially retained in the joints formed at 125 and 150V. The amount of martensite observed near the joint interface increased with the charged voltage. The ferrite was not observed above 175V in the center, and above 150V inside and outside of the projection near the joint interface. To estimate the maximum temperature reached during joining, the microstructures of the stud and plate heated at various temperatures were compared with those of joint specimens. Because ferrite and martensite was observed near the joint interface, the maximum temperature reached during joining could be estimated by the presence or absence of the ferrite and martensite. The region where the temperature increased above the A1point extended only about 500μm around the joint interface. Because the majority of the specimen was room temperature and removed heat rapidly from the joint interface, martensite was formed despite the air cooling after joining. The tensile fracture load increased with the charged voltage. The stud and plate were joined strongly enough for the base plate to fracture partially during the tensile test.

The aim of this study was to investigate a cell delivery system for repair of severe chronic osteochondral defects using magnetically labeled mesenchymal stem cells (m-MSCs), with the aid of an external magnetic device, through the accumulation of a small number of m-MSCs into a desired area and to detect the suitable number of autologous m-MSCs needed for repair of the defect. Twenty-six male Japanese white rabbits aged 6 months were used. An osteochondral defect was created bilaterally at the weight-bearing surface of the medial femoral condyle of the rabbits' knees (3 mm diameter; 4 mm depth). At 4 weeks after creation of the defect, autogenic transplantation of the m-MSCs into the defect area was performed, followed by 10-min exposure to an external magnetic device, where animals were divided into four groups: high (1 × 106m-MSCs), medium (2 × 105m-MSCs), low (4 × 104m-MSCs), and control (PBS injection). At 4 and 12 weeks posttransplantation of m-MSCs, repaired tissue was assessed histologically using the Fortier score with toluidine blue staining. Transplantation of a low number of m-MSCs was not enough to improve osteogenesis and chondrogenesis, but the medium and high groups improved repair of the chronic defect with chondrogenic tissues and showed histologically significantly better results than the control and low groups. The use of a magnetic targeting system for delivering m-MSCs has the potential to overcome the clinical hurdles for repair of the severe chronic osteochondral defect. Furthermore, this system is predicted to produce good clinical outcomes for humans, not only to repair osteochondral defects but also to repair a variety of damaged tissues.

High strength 2024 aluminum alloy studs were joined to galvanized, galvannealed and non-coated steel sheets by using an advanced stud welding method. Effect of the coating layer on the interfacial microstructure and the tensile fracture load of the joints were evaluated. A specially-designed stud having a circular projection at its bottom was pressed against a sheet surface. A discharge current was introduced from the upper part of the stud. Local heating could be achieved by a high current density at a contact point between the projection and sheet. The observation of joint area revealed the projection was severely deformed and spread along the sheet surface. The coating layer of the galvanized steel sheet was removed at the joint interface under the charging voltage of 200 V, while that of the galvannealed one locally remained on the steel surface even at 400 V. This would be strongly related to the melting or liquidus and solidus temperatures of each coating layer. Joining was not achieved at a low charging voltage in the non-coated and galvannealed steel sheets, while high tensile fracture load was obtained even at 200 V in the galvanized ones.

The impact welding was performed for several kinds of metal plate couples. The joint interface exhibited a sinusoidal wave form when two metal plates with the same or similar density (e.g. Al/Al, Cu/Cu and Cu/Ni) were impact-welded by high-speed oblique collision. In contrast, as for dissimilar metal plate couples with large density difference such as Al/Cu, an asymmetric wavy interface was obtained. In order to make clear the reason for morphological difference, a computer simulation of the collision behavior was performed using SPH (Smooth Particle Hydrostatic) method. The simulation results revealed that the wave form was controlled by the interaction between the emitted metal jet and metal plate surfaces ahead of the collision point. For Al/Al and Cu/Ni, the emitted metal jet hit each surface alternatively and this resulted in symmetrical wavy interface formation. While, for Al/Cu, the metal jet was emitted to the direction parallel to the Cu plate, and the interaction took place between the metal jet and the Cu plate surface. The metal jet emission and wavy interface formation mechanism were also investigated.

An A356 aluminum alloy billet which has a dendritic microstructure was compressed and then partially re-melted to semi-solid state before water quenching, by which the spheroidization of Al grains was realized. A color etchant called Weck's reagent was used to characterize both the dendritic and spheroidal microstructure. In both cases, distinct color differences were observed inside Al grains by normal optical microscopy. Interestingly, a dendritic-shaped structure inside the spheroidal Al grains was visualized, which should be the reflection of the original dendrite before heating and partial re-melting. Also, the grain growth during water quenching could be clearly visualized after etching with this reagent. As a result, solid fractions could be evaluated more precisely by excluding the grain growth when measuring the area of solid phase in 2-D micrographs. In order to investigate the coloring mechanism, electron probe micro-analyses were carried out to characterize the micro-segregations inside an Al grain. Results showed that the micro-segregation of Ti had a strong correlation with the color difference. Detailed investigation found that the micro-segregation of Ti could be preserved after heating and partial re-melting due to the extremely low diffusion rate of Ti in Al.

Right- and left-side throwers in baseball may have different shoulder conditions and throwing biomechanics. This study aimed to compare the passive range of motion, humeral torsion, and clinical findings between right- and left-handed throwers who sustained throwing shoulder injuries and confirming the differences in the characteristics between throwing sides.

Exogenous lipoid pneumonia (ELP) develops when lipid-containing substances enter the airways through aspiration or inhalation and incite an inflammatory response. The diagnosis of ELP often is difficult because findings may be nonspecific. The clinical course of ELP has not been well characterized.

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