Impairment of Pattern Separation of Ambiguous Scenes by Single Units in the CA3 in the Absence of the Dentate Gyrus.

Theoretical models and experimental evidence have suggested that connections from the dentate gyrus (DG) to CA3 play important roles in representing orthogonal information (i.e., pattern separation) in the hippocampus. However, the effects of eliminating the DG on neural firing patterns in the CA3 have rarely been tested in a goal-directed memory task that requires both the DG and CA3. In this study, selective lesions in the DG were made using colchicine in male Long-Evans rats, and single units from the CA3 were recorded as the rats performed visual scene memory tasks. The original scenes used in training were altered during testing by blurring to varying degrees or by using visual masks, resulting in maximal recruitment of the DG-CA3 circuits. Compared with controls, the performance of rats with DG lesions was particularly impaired when blurred scenes were used in the task. In addition, the firing rate modulation associated with visual scenes in these rats was significantly reduced in the single units recorded from the CA3 when ambiguous scenes were presented, largely because DG-deprived CA3 cells did not show stepwise, categorical rate changes across varying degrees of scene ambiguity compared with controls. These findings suggest that the DG plays key roles not only during the acquisition of scene memories but also during retrieval when modified visual scenes are processed in conjunction with the CA3 by making the CA3 network respond orthogonally to ambiguous scenes.SIGNIFICANCE STATEMENT Despite the behavioral evidence supporting the role of the dentate gyrus in pattern separation in the hippocampus, the underlying neural mechanisms are largely unknown. By recording single units from the CA3 in DG-lesioned rats performing a visual scene memory task, we report that the scene-related modulation of neural firing was significantly reduced in the DG-lesion rats compared with controls, especially when the original scene stimuli were ambiguously altered. Our findings suggest that the dentate gyrus plays an essential role during memory retrieval and performs a critical computation to make categorical rate modulation occur in the CA3 between different scenes, especially when ambiguity is present in the environment.

Goal-directed interaction of stimulus and task demand in the parahippocampal region.

The hippocampus and parahippocampal region are essential for representing episodic memories involving various spatial locations and objects, and for using those memories for future adaptive behavior. The "dual-stream model" was initially formulated based on anatomical characteristics of the medial temporal lobe, dividing the parahippocampal region into two streams that separately process and relay spatial and nonspatial information to the hippocampus. Despite its significance, the dual-stream model in its original form cannot explain recent experimental results, and many researchers have recognized the need for a modification of the model. Here, we argue that dividing the parahippocampal region into spatial and nonspatial streams a priori may be too simplistic, particularly in light of ambiguous situations in which a sensory cue alone (e.g., visual scene) may not allow such a definitive categorization. Upon reviewing evidence, including our own, that reveals the importance of goal-directed behavioral responses in determining the relative involvement of the parahippocampal processing streams, we propose the Goal-directed Interaction of Stimulus and Task-demand (GIST) model. In the GIST model, input stimuli such as visual scenes and objects are first processed by both the postrhinal and perirhinal cortices-the postrhinal cortex more heavily involved with visual scenes and perirhinal cortex with objects-with relatively little dependence on behavioral task demand. However, once perceptual ambiguities are resolved and the scenes and objects are identified and recognized, the information is then processed through the medial or lateral entorhinal cortex, depending on whether it is used to fulfill navigational or non-navigational goals, respectively. As complex sensory stimuli are utilized for both navigational and non-navigational purposes in an intermixed fashion in naturalistic settings, the hippocampus may be required to then put together these experiences into a coherent map to allow flexible cognitive operations for adaptive behavior to occur.

Room Temperature Intrinsic Ferromagnetism in Epitaxial Manganese Selenide Films in the Monolayer Limit.

Monolayer van der Waals (vdW) magnets provide an exciting opportunity for exploring two-dimensional (2D) magnetism for scientific and technological advances, but the intrinsic ferromagnetism has only been observed at low temperatures. Here, we report the observation of room temperature ferromagnetism in manganese selenide (MnSe x) films grown by molecular beam epitaxy (MBE). Magnetic and structural characterization provides strong evidence that, in the monolayer limit, the ferromagnetism originates from a vdW manganese diselenide (MnSe2) monolayer, while for thicker films it could originate from a combination of vdW MnSe2 and/or interfacial magnetism of α-MnSe(111). Magnetization measurements of monolayer MnSe x films on GaSe and SnSe2 epilayers show ferromagnetic ordering with a large saturation magnetization of ∼4 Bohr magnetons per Mn, which is consistent with the density functional theory calculations predicting ferromagnetism in monolayer 1T-MnSe2. Growing MnSe x films on GaSe up to a high thickness (∼40 nm) produces α-MnSe(111) and an enhanced magnetic moment (∼2×) compared to the monolayer MnSe x samples. Detailed structural characterization by scanning transmission electron microscopy (STEM), scanning tunneling microscopy (STM), and reflection high energy electron diffraction (RHEED) reveals an abrupt and clean interface between GaSe(0001) and α-MnSe(111). In particular, the structure measured by STEM is consistent with the presence of a MnSe2 monolayer at the interface. These results hold promise for potential applications in energy efficient information storage and processing.

Restoration of a large osteochondral defect of the knee using a composite of umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel: a case report with a 5-year follow-up.

BACKGROUND: The treatment of articular cartilage defects is a therapeutic challenge for orthopaedic surgeons. Furthermore, large osteochondral defects needs restoration of the underlying bone for sufficient biomechanical characteristics as well as the overlying cartilage. CASE PRESENTATION: A symptomatic large osteochondral defect in the knee joint was restored using a composite of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) 0.5 x 107/ml and 4% hyaluronic acid (HA) hydrogel. Significant improvements in pain and function of the knee joint were identified by the evaluation at 12 months after surgery. A hyaline-like cartilage completely filled the defect and was congruent with the surrounding normal cartilage as revealed by magnetic resonance imaging (MRI), a second-look arthroscopy and histological assessment. The improved clinical outcomes maintained until 5.5 years. MRI also showed the maintenance of the restored bony and cartilaginous tissues. CONCLUSION: This case report suggests that the composite of allogeneic UCB-MSCs and HA hydrogel can be considered a safe and effective treatment option for large osteochondral defects of the knee.

Functional cross-hemispheric shift between object-place paired associate memory and spatial memory in the human hippocampus.

The hippocampus plays critical roles in both object-based event memory and spatial navigation, but it is largely unknown whether the left and right hippocampi play functionally equivalent roles in these cognitive domains. To examine the hemispheric symmetry of human hippocampal functions, we used an fMRI scanner to measure BOLD activity while subjects performed tasks requiring both object-based event memory and spatial navigation in a virtual environment. Specifically, the subjects were required to form object-place paired associate memory after visiting four buildings containing discrete objects in a virtual plus maze. The four buildings were visually identical, and the subjects used distal visual cues (i.e., scenes) to differentiate the buildings. During testing, the subjects were required to identify one of the buildings when cued with a previously associated object, and when shifted to a random place, the subject was expected to navigate to the previously chosen building. We observed that the BOLD activity foci changed from the left hippocampus to the right hippocampus as task demand changed from identifying a previously seen object (object-cueing period) to searching for its paired-associate place (object-cued place recognition period). Furthermore, the efficient retrieval of object-place paired associate memory (object-cued place recognition period) was correlated with the BOLD response of the left hippocampus, whereas the efficient retrieval of relatively pure spatial memory (spatial memory period) was correlated with the right hippocampal BOLD response. These findings suggest that the left and right hippocampi in humans might process qualitatively different information for remembering episodic events in space. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Selective Medial Release Technique Using the Pie-Crusting Method for Medial Tightness During Primary Total Knee Arthroplasty.

BACKGROUND: The pie-crusting method is popular in releasing lateral tightness during primary total knee arthroplasty (TKA) but is not well described for medial release. We established a selective medial release technique using the pie-crusting technique and investigated the effectiveness and safety of the technique during primary TKA. METHODS: We retrospectively reviewed 729 primary TKAs with varus deformity between October 2009 and June 2012. Medial tightness in flexion was released by traditional subperiosteal stripping for the anterior portion of the medial collateral ligament (aMCL). Medial tightness in extension was released by the pie crusting for the tight fibers in the posterior portion of the MCL and/or posteromedial corner structures (pMCL/PMCS). Clinical outcomes were evaluated by Knee Society (KS) scores and the Western Ontario and McMaster Universities Osteoarthritis Index. Any complications, including late medial instability that may be related to our surgical technique, were carefully inspected. RESULTS: Among the 729 knees, 170 (23.3%) required subperiosteal stripping for balancing in flexion only, 186 (25.5%) required the pie-crusting for balancing in extension only and 142 (19.5%) required subperiosteal stripping and the pie-crusting for balancing in flexion and extension. The KS knee score was improved from 52.5 to 83.4, KS function score from 58.2 to 91.9, and Western Ontario and McMaster Universities Osteoarthritis Index from 42.7 to 21.8 (P < .001, all). No specific complications related to our technique were identified. CONCLUSIONS: The selective medial release technique appears to be an effective and safe method to obtain a balanced mediolateral gap in primary TKA.

Performing high flexion activities does not seem to be crucial in developing early femoral component loosening after high-flexion TKA.

BACKGROUND: It is still unclear whether high flexion (HF) activities correlated with the early loosening of the femoral component and whether HF activities are possible. We investigated what is the capability for performing various HF activities, and whether high flexion activities increase the chance of aseptic loosening after HF-TKA. METHODS: We retrospectively analysed 260 patients who underwent HF-TKA using the NexGen LPS Flex between 2001 and 2009. The mean follow-up was 6.7 years (range, 5-13). We evaluated range of motion, Knee Society scores, WOMAC, and serial radiographs for aseptic loosening. Responses to questions on individual HF activities were recorded on 5-point Likert scales based on difficulty (0-4). Patients were divided two groups based on their responses to squatting and kneeling, which were important weight-bearing HF activities in Asian population (HF group vs. non-HF group) for comparisons of aseptic loosening and clinical outcomes. RESULTS: More than 80 % of patients positively responded for various HF activities. The capability of HF activities showed that cross-legged sitting, squatting, and kneeling were 97.7, 51.1 and 52.7 % at the latest follow-up, respectively. Aseptic loosening was identified in two tibial components (0.8 %) but none in femoral components in non-HF group. There was no significant difference of aseptic loosening based on HF activities (0.8% vs. 0%, p = 0.063). CONCLUSIONS: The results of this study suggest that HF activities do not seem to be associated with aseptic loosening of femoral component after HF-TKA.

A new high-flexion knee scoring system to eliminate the ceiling effect.

BACKGROUND: Various scoring systems document improvement after TKA, but most are associated with a ceiling effect that may fail to distinguish between patients having different levels of knee function after TKA. We therefore developed a new scoring system for patients with higher levels of flexion to eliminate ceiling effects observed with current systems. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine whether the high-flexion knee score eliminates the ceiling effect, (2) to assess the validity and responsiveness of the high-flexion knee score, and (3) to determine whether the high-flexion knee score can aid in differentiation of the knee status of patients at the ceiling level. METHODS: We prospectively studied 165 patients with 201 well-functioning knees who had undergone primary TKA. We obtained Knee Society scores, WOMAC scores, Feller scores, SF-36 scores, and high-flexion knee scores for all patients. The high-flexion knee score includes items that reflect knee function in the high functional range, such as sitting on or rising from the floor, squatting, or kneeling. We determined the ceiling effects and score distributions of various scoring systems. We performed a convergent validity test of the high-flexion knee score by correlation analysis with these various scoring systems. Responsiveness of the high-flexion knee score was assessed by correlation analysis of changes in various scoring systems. To determine whether the high-flexion knee score can aid in differentiation of knee status of patients at the ceiling level, relative responsiveness of the various scores in the ceiling versus below the ceiling range was determined. RESULTS: The high-flexion knee score showed no ceiling effect, whereas the other systems did. Addition of the high-flexion knee score to the other scoring systems eliminated these ceiling effects and resulted in more normalized score distributions. The high-flexion knee score correlated (r = -0.77) with WOMAC in postoperative scores, and it also correlated with the changes in WOMAC (r = -0.69) and SF-36 physical functioning (r = 0.62). The correlation of WOMAC score with SF-36 physical function score was lower in patients at the ceiling level of the Knee Society knee score and Knee Society function score, compared with the correlation at below-ceiling range, whereas the high-flexion knee score maintained a correlation with the SF-36 physical function score, even at the ceiling level of the Knee Society knee score and Knee Society function score. CONCLUSIONS: Compared with other systems, the high-function knee score appears valid for evaluating the knee status in the high-flexion range. Our data suggest the high-flexion knee score differentiates among the knee status in the high-function range. Furthermore, the high-function knee score eliminates the ceiling effect of the currently used scoring tools, and thus may be useful when combined with other scoring systems. LEVEL OF EVIDENCE: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Role of anterior cingulate cortex inputs to periaqueductal gray for pain avoidance.

Although pain-related excessive fear is known to be a key factor in chronic pain disability, which involves the anterior cingulate cortex (ACC), little is known about the downstream circuits of the ACC for fear avoidance in pain processing. Using behavioral experiments and functional magnetic resonance imaging with optogenetics at 15.2 T, we demonstrate that the ACC is a part of the abnormal circuit changes in chronic pain and its downstream circuits are closely related to modulating sensorimotor integration and generating active movement rather than carrying sensory information. The projection from the ACC to the dorsolateral and lateral parts of the periaqueductal gray (dl/lPAG) especially enhances both reflexive and active avoidance behavior toward pain. Collectively, our results indicate that increased signals from the ACC to the dl/lPAG might be critical for excessive fear avoidance in chronic pain disability.

Cartilage Regeneration in Osteoarthritic Patients by a Composite of Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronate Hydrogel: Results from a Clinical Trial for Safety and Proof-of-Concept with 7 Years of Extended Follow-Up.

Few methods are available to regenerate articular cartilage defects in patients with osteoarthritis. We aimed to assess the safety and efficacy of articular cartilage regeneration by a novel medicinal product composed of allogeneic human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Patients with Kellgren-Lawrence grade 3 osteoarthritis and International Cartilage Repair Society (ICRS) grade 4 cartilage defects were enrolled in this clinical trial. The stem cell-based medicinal product (a composite of culture-expanded allogeneic hUCB-MSCs and hyaluronic acid hydrogel [Cartistem]) was applied to the lesion site. Safety was assessed by the World Health Organization common toxicity criteria. The primary efficacy outcome was ICRS cartilage repair assessed by arthroscopy at 12 weeks. The secondary efficacy outcome was visual analog scale (VAS) score for pain on walking. During a 7-year extended follow-up, we evaluated safety, VAS score, International Knee Documentation Committee (IKDC) subjective score, magnetic resonance imaging (MRI) findings, and histological evaluations. Seven participants were enrolled. Maturing repair tissue was observed at the 12-week arthroscopic evaluation. The VAS and IKDC scores were improved at 24 weeks. The improved clinical outcomes were stable over 7 years of follow-up. The histological findings at 1 year showed hyaline-like cartilage. MRI at 3 years showed persistence of the regenerated cartilage. Only five mild to moderate treatment-emergent adverse events were observed. There were no cases of osteogenesis or tumorigenesis over 7 years. The application of this novel stem cell-based medicinal product appears to be safe and effective for the regeneration of durable articular cartilage in osteoarthritic knees. Stem Cells Translational Medicine 2017;6:613-621.

Antioxidant Activity of Brown Soybean Ethanolic Extracts and Application to Cooked Pork Patties.

The brown soybean extract (BE, extracted by distilled water, 50%, 75%, and 95% ethanol) were analyzed for their total phenol, flavonoid, anthocyanin content, and DPPH radical-scavenging activity to determine antioxidant activities. Brown soybean extract with 75% ethanol showed significantly higher DPPH radical scavenging activity, total phenol and anthocyanin content compared to the other treatments (p<0.05). Then, brown soybean extract with 75% ethanol was applied to pork patties at different concentration (0.05%, 0.1%, and 0.2%) and lipid oxidation was evaluated during 15 d of refrigerated storage. Addition of BE significantly increased redness and pH values, respectively (p<0.05). Moreover, TBARS value of pork patties decreased significantly (p<0.05) as BE concentration increased. In sensory evaluation, pork patties with 0.1% BE had significantly higher score than other treatments in flavor and overall acceptability (p<0.05). Consequently, these results indicate that 0.1% BE could be an effective natural antioxidant to inhibit lipid oxidation in pork patties.

Cartilage repair by human umbilical cord blood-derived mesenchymal stem cells with different hydrogels in a rat model.

This study was carried out to assess the feasibility of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in articular cartilage repair and to further determine a suitable delivering hydrogel in a rat model. Critical sized full thickness cartilage defects were created. The hUCB-MSCs and three different hydrogel composites (hydrogel A; 4% hyaluronic acid/30% pluronic (1:1, v/v), hydrogel B; 4% hyaluronic acid, and hydrogel C; 4% hyaluronic acid/30% pluronic/chitosan (1:1:2, v/v)) were implanted into the experimental knee (right knee) and hydrogels without hUCB-MSCs were implanted into the control knee (left knee). Defects were evaluated after 8 weeks. The hUCB-MSCs with hydrogels composites resulted in a better repair as seen by gross and histological evaluation compared with hydrogels without hUCB-MSCs. Among the three different hydrogels, the 4% hyaluronic acid hydrogel composite (hydrogel B) showed the best result in cartilage repair as seen by the histological evaluation compared with the other hydrogel composites (hydrogel A and C). The results of this study suggest that hUCB-MSCs may be a promising cell source in combination with 4% hyaluronic acid hydrogels in the in vivo repair of cartilage defects.

Effects of Glasswort (Salicornia herbacea L.) Hydrates on Quality Characteristics of Reduced-salt, Reduced-fat Frankfurters.

This study evaluated the effects of adding glasswort hydrate containing non-meat ingredient (GM, carboxy methyl cellulose; GC, carrageenan; GI, isolated soy protein; GS, sodium caseinate) on the quality characteristics of reduced-salt, reduced-fat frankfurters. The pH and color evaluation showed significant differences, depending on the type of glasswort hydrate added (p<0.05). In the raw batters and cooked frankfurters, the addition of glasswort hydrate decreased the redness and increased the yellowness in comparison with frankfurters without glasswort hydrate. The reduction in salt and fat content significantly increased cooking loss and decreased hardness, tenderness and juiciness (p<0.05). Glasswort hydrate containing non-meat ingredient improved cooking loss, water holding capacity, emulsion stability, hardness, and viscosity of reduced-salt, reduced-fat frankfurters. The GM treatment had the highest myofibiliar protein solubility among all treatments, which was associated with emulsion stability and viscosity. The GC treatment had higher values for all texture parameters than the control. In the sensory evaluation, the addition of glasswort hydrate with non-meat ingredient improved tenderness and juiciness of reduced-salt, reduced-fat frankfurters. GM, GC, and GI treatments improved not only the physicochemical properties but also the sensory characteristics of reduced-salt, reduced-fat frankfurters. The results indicated that the use of glasswort hydrate containing non-meat ingredient was improved the quality characteristics of reduced-salt, reduced-fat frankfurters.

Comparison of articular cartilage repair with different hydrogel-human umbilical cord blood-derived mesenchymal stem cell composites in a rat model.

INTRODUCTION: The present work was designed to explore the feasibility and efficacy of articular cartilage repair using composites of human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) and four different hydrogels in a rat model. METHODS: Full-thickness articular cartilage defects were created at the trochlear groove of femur in both knees of rats. Composites of hUCB-MSCs and four different hydrogels (group A, 4% hyaluronic acid; group B, 3% alginate:30% pluronic (1:1, v/v); group C, 4% hyaluronic acid: 3% alginate: 20% pluronic (2:1:1, v/v}; and group D, 4% hyaluronic acid:3% alginate:20% pluronic;chitosan (4:1:1:2, v/v).) were then transplanted into right knee defect in each study group (five rats/group). Left knees were transplanted with corresponding hydrogels without hUCB-MSCs as controls. At 16 weeks post-transplantation, degrees of cartilage repair were evaluated macroscopically and histologically using Masson's Trichrome, safranin-O, Sirius red staining, and type-II collagen immunostaining. RESULTS: Overall, group A with 4% hyaluronic acid hydrogel resulted in superior cartilage repair grossly and histologically and achieved a cellular arrangement and collagen organization pattern mimicking adjacent uninjured articular cartilage. Immunostaining and safranin-O staining also revealed that group A displayed the largest areas of type II collagen staining. Sirius red staining revealed that the organization pattern of collagen bundles was more similar to normal cartilage in group A. No evidence of rejection was found. CONCLUSIONS: The results of this study suggest that hUCB-MSCs could be used to repair articular cartilage defects in vivo and that hyaluronic acid is an attractive hydrogel candidate for use in combination with hUCB-MSCs.

Application of Ganghwa Mugwort in Combination with Ascorbic Acid for the Reduction of Residual Nitrite in Pork Sausage during Refrigerated Storage.

The application of ganghwa mugwort (GM), ascorbic acid (AC), and their combinations for reduction of residual nitrite contents was analyzed in pork sausages during storage of 28 d. Six treatments of pork sausages contained the following: Control (no antioxidant added), AC (0.05% AC), GM 0.1 (0.1% GM), GM 0.2 (0.2% GM), AC+GM 0.1 (0.05% AC + 0.1% GM) and AC+GM 0.2 (0.05% AC + 0.2% GM). Results showed that the mixture of 0.05% AC and 0.2% GM was most effective for reducing thiobarbituric acid reactive substances (TBARS) and residual nitrite contents than the control and GM added sausages alone (p<0.05). The color values of all treatments were significantly affected by adding GM (either alone or with AC). Additionally, the total color difference (ΔE) and hue angle (H°) values of treatments added with GM were higher than those of the control as the amount of GM increased (p<0.05). However, there were no significant differences in the pH values between the control and all treatments during the storage period (p>0.05). Our results showed possible applications of antioxidant combination, for preventing the lipid oxidation and decreasing the residual nitrite levels of meat products.

Contextual behavior and neural circuits.

Animals including humans engage in goal-directed behavior flexibly in response to items and their background, which is called contextual behavior in this review. Although the concept of context has long been studied, there are differences among researchers in defining and experimenting with the concept. The current review aims to provide a categorical framework within which not only the neural mechanisms of contextual information processing but also the contextual behavior can be studied in more concrete ways. For this purpose, we categorize contextual behavior into three subcategories as follows by considering the types of interactions among context, item, and response: contextual response selection, contextual item selection, and contextual item-response selection. Contextual response selection refers to the animal emitting different types of responses to the same item depending on the context in the background. Contextual item selection occurs when there are multiple items that need to be chosen in a contextual manner. Finally, when multiple items and multiple contexts are involved, contextual item-response selection takes place whereby the animal either chooses an item or inhibits such a response depending on item-context paired association. The literature suggests that the rhinal cortical regions and the hippocampal formation play key roles in mnemonically categorizing and recognizing contextual representations and the associated items. In addition, it appears that the fronto-striatal cortical loops in connection with the contextual information-processing areas critically control the flexible deployment of adaptive action sets and motor responses for maximizing goals. We suggest that contextual information processing should be investigated in experimental settings where contextual stimuli and resulting behaviors are clearly defined and measurable, considering the dynamic top-down and bottom-up interactions among the neural systems for contextual behavior.

A novel patellofemoral scoring system for patellofemoral joint status.

BACKGROUND: We were not aware of a well-validated patellofemoral joint-specific scoring system. We performed this study to develop and validate a scoring system (Samsung Medical Center [SMC] patellofemoral scoring system) suitable for the evaluation of patellofemoral joint status. METHODS: We recruited 179 individuals consisting of a study group of 123 patients with anterior knee pain but without pain in another part of the knee, twenty-eight patients with knee pain other than anterior knee pain (group A), and twenty-eight healthy volunteers without knee pain (group B). Items in the development of the scoring system that showed a significant difference between the study group and group A and between the study group and the group B were selected. Test-retest reliability was measured by intraclass correlation coefficient, internal consistency was measured by the Cronbach alpha, content validity was assessed by ceiling and floor effects, and construct validity was determined by the association of the Feller scores and the SMC patellofemoral scores. RESULTS: After the item verification process, seventeen items (eight items for patellofemoral pain and nine items for patellofemoral function) were selected. Test-retest reliability for overall SMC patellofemoral scores showed excellent reliability (intraclass correlation coefficient, 0.85), and internal consistency was excellent (Cronbach alpha, 0.97). Floor and ceiling effects were acceptable (<30%) for all the items of the SMC patellofemoral scoring system, except one: sitting down on a chair, in the patellofemoral function score. The SMC patellofemoral scores showed moderate correlation with the Feller scores (ρ = -0.45). CONCLUSIONS AND CLINICAL RELEVANCE: The SMC patellofemoral score is a novel scoring system that distinguishes patients with anterior knee pain or patellofemoral dysfunction from patients with knee pain or dysfunction arising from other knee problems, and from those without knee pain. The reliability and validity of the SMC patellofemoral scoring system were verified in the present study.

Comparison of robot-assisted and conventional total knee arthroplasty: a controlled cadaver study using multiparameter quantitative three-dimensional CT assessment of alignment.

INTRODUCTION: A functional total knee replacement has to be well aligned, which implies that it should lie along the mechanical axis and in the correct axial and rotational planes. Incorrect alignment will lead to abnormal wear, early mechanical loosening, and patellofemoral problems. There has been increased interest of late in total knee arthroplasty with robotic assistance. This study was conducted to determine whether robot-assisted total knee arthroplasty is superior to the conventional surgical method with regard to the precision of implant positioning. MATERIALS AND METHODS: Twenty knee replacements, comprising ten robot-assisted procedures and ten conventional operations, were performed on ten cadavers. Two experienced surgeons performed the surgeries. Both procedures on each cadaver were performed by the same surgeon. The choice of which procedure was to be performed first was randomized. Following implantation of the prosthesis, the mechanical axis deviation, femoral coronal angle, tibial coronal angle, femoral sagittal angle, tibial sagittal angle, and femoral rotational alignment were measured via 3D CT scanning. These variables were then compared with the preoperatively planned values. RESULTS: In the knees that underwent robot-assisted surgery, the mechanical axis deviation ranged from -1.94° to 2.13° (mean: -0.21°), the femoral coronal angle from 88.08° to 90.99° (mean: 89.81°), the tibial coronal angle from 89.01° to 92.36° (mean: 90.42°), the tibial sagittal angle from 81.72° to 86.24° (mean: 83.20°), and the femoral rotational alignment from 0.02° to 1.15° (mean: 0.52°) in relation to the transepicondylar axis. In the knees that underwent conventional surgery, the mechanical axis deviation ranged from -3.19° to 3.84° (mean: -0.48°), the femoral coronal angle from 88.36° to 92.29° (mean: 90.50°), the tibial coronal angle from 88.15° to 91.51° (mean: 89.83°), the tibial sagittal angle from 80.06° to 87.34° (mean: 84.50°), and the femoral rotational alignment from 0.32° to 4.13° (mean: 2.76°) in relation to the transepicondylar axis. In the conventional knee replacement group, there were two instances of outliers outside the range of 3° varus/valgus for the mechanical axis deviation. The robot-assisted knee replacements showed significantly superior femoral rotational alignment results compared with conventional surgery (p = 0.006). There was no statistically significant difference between robot-assisted and conventional total knee arthroplasty with regard to the other variables. All the measurements showed high intra-observer and inter-observer reliability. CONCLUSION: Robot-assisted total knee arthroplasty showed excellent precision in the sagittal and coronal planes of the 3D CT scan. In particular, the robot-assisted technique showed better accuracy in femoral rotational alignment compared to the conventional surgery, despite the fact that the surgeons who performed the operations were more experienced and familiar with the conventional method than with robot-assisted surgery. It can thus be concluded that robot-assisted total knee arthroplasty is superior to conventional total knee arthroplasty.

Identification of genetic polymorphisms of human OAT1 and OAT2 genes and their relationship to hOAT2 expression in human liver.

BACKGROUND: Organic anion transporters (OATs) play an essential role in the disposition of numerous organic anions. To clarify the interindividual variation in the function of OATs, genetic polymorphisms of the SLC22A6 and SLC22A7 in Korean subjects were investigated and associated with hepatic hOAT2 expression and the SLC22A7 genotype. METHODS: The genetic variants and their frequencies for the SLC22A6 and SLC22A7 genes in 50 Korean subjects were investigated by direct sequencing. The expression of hOAT2 protein from 34 human liver samples was examined by western blot analysis. RESULTS: Eight SNPs including 2 novel SNPs were identified in the SLC22A6 gene and eight SNPs including 4 novel SNPs were identified in the SLC22A7 gene. No amino acid alteration was found. Linkage disequilibrium (LD) analysis revealed that the SLC22A6 and SLC22A7 genes have separated single LD blocks and consist of a limited number of haplotypes (14 haplotypes for SLC22A6 and 5 haplotypes for SLC22A7). The expression of the hOAT2 protein varied 10-fold among 34 human livers but was not associated with the SLC22A7 genotype (p=0.16). CONCLUSIONS: The SLC22A7 genomic sequences showed low variability. A 10-fold variation in hOAT2 protein expression in the liver specimens was not correlated with SLC22A7 genotypes. These results suggest that genetic polymorphisms may not be a significant contributing factor to variations in the hOAT2 expression or hOAT2 transport activity.

Establishment and characterization of Mardin-Darby canine kidney cells stably expressing human organic anion transporters.

Organic anion transporters (OATs) play essential roles in the renal elimination of clinically important anionic drugs. The purpose of this study was to establish an efficient in vitro assay system to screen the transport characteristics of drugs and to examine drug interaction potentials of drugs with OATs. First, we established Mardin-Darby canine kidney (MDCK) cells stably expressing OAT1, OAT3, and OAT4 (MDCK-OAT1, -OAT3, and -OAT4, respectively). To characterize these cells, [(14)C]para-aminohippuric acid and [(3)H]estrone-3-sulfate transport properties were measured, and these corresponded to the results of the mRNA expression and localization of respective transporters using RT-PCR and immunofluorescence staining assay. Additionally, we screened three herbal medicines, Woohwangcheongsimwon, Hawangyeonhaedoktang, and Aristolochiae fructus extracts, which have been widely used in Korea or reported for nephrotoxicity, in our MDCK-OAT1, -OAT3, and -OAT4 cells. Aristolochiae fructus extracts strongly inhibited organic anion uptake by OAT1, OAT3, and OAT4, whereas Woohwangcheongsimwon only interacted with OAT1, and Hawangyeonhaedoktang with OAT1 and OAT3, suggesting drug interaction potential with OATs-mediated renal eliminating drugs. In conclusion, we established and characterized MDCK cells stably expressing OAT1, OAT3, and OAT4 for the elucidation of substrates or inhibitors of respective transporters as high-throughput screening tools.