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Background Post-arthroscopic osteonecrosis of the knee (PAONK) is a rare condition. No studies have analyzed the relationship between the meniscus extrusion and PAONK. The purpose of this retrospective study is to test a hypothesis that the degree of the medial meniscus (MM) extrusion might be significantly greater in the knees with PAONK than in the matched control knees both before and after the meniscectomy. Methods Ten knees with PAONK were detected out of a total of 876 knees which had undergone arthroscopic partial meniscectomy of the MM. Ten matched control knees were randomly selected out of the remaining 866 knees without PAONK. The clinical data of these 20 patients were retrospectively collected from the medical records. To evaluate the location of the menisci on the joint line, Extrusion width and Inner width were defined on a coronal section of magnetic resonance imaging (MRI). The intra- and inter-rater reliability was evaluated by calculating the intra- and inter-class coefficients. Statistical comparisons between the 2 groups were made using the 3 non-parametric tests. Results Before the meniscectomy, the Extrusion width of the MM (mean 4.7 ± 1.4 mm) was significantly greater than that (3.0 ± 1.3 mm) in the Control group (P = 0.0195). In the MRI taken in a range from 3 to 50 weeks after the meniscectomy, the Extrusion width of the MM (5.9 ± 1.1 mm) in the PAONK group was significantly greater than that (3.4 ± 1.4 mm) in the Control group (P = 0.0009), and the Inner width of the MM (0.6 ± 1.7 mm) in the PAONK group was significantly less than that (3.9 ± 1.0 mm) in the Control group (P = 0.0001). Conclusion A significant relationship was found between the degree of the MM extrusion and the onset of PAONK. This study suggested that the extrusion of the MM is a potential predisposing factor for PAONK.

Background: A fibular shortening osteotomy is needed to perform lateral closing-wedge high tibial osteotomy (LCW-HTO). To achieve this shortening, we have recently developed an acute oblique osteotomy and ligation (AO/L) procedure for the center of the fibular shaft, based on the AO procedure. Purpose: To compare the 2-year follow-up outcomes between the AO/L procedure and the AO procedure. Study Design: Cohort study; Level of evidence, 2. Methods: A prospective comparative cohort study was conducted involving 83 patients (83 knees) who underwent shortening osteotomy of the fibula in LCW-HTO between April 2017 and March 2019. The first consecutive 41 knees (AO group) underwent fibular osteotomy with the AO procedure. The remaining 42 knees (AO/L group) underwent fibular osteotomy with the AO/L procedure. All of the patients were evaluated for at least 2 years postoperatively via clinical and radiological assessments. To determine the time needed for complete union at the osteotomy site, we evaluated the radiographs using a radiographic union score for tibial fractures, which was modified for fibular osteotomy. Comparison of outcomes between the 2 groups was performed using the Student t test for continuous variables and the Mann-Whitney U test or Fisher exact test for discrete variables. Results: Around the fibular osteotomy site, no perioperative complications were found in either group. The radiographic union score was significantly higher in the AO/L group than in the AO group ( P < .0001 at 2, 3, and 6 months; P = .0290 at 12 and 24 months). The union rate at the fibular osteotomy site was significantly higher in the AO/L group (97.6%) than in the AO group (82.9%) at 12 months ( P = .0290). Conclusion: The AO/L procedure significantly accelerated the formation of bridging callus at the fibular osteotomy site and provided a significantly higher union rate compared with the AO procedure. Both AO/L and AO procedures were free from perioperative complications. These results suggest that the AO/L procedure is clinically useful as an osteotomy procedure to shorten the fibula in LCW-HTO.

Background: Medial open-wedge high tibial osteotomy (OWHTO) theoretically causes distalization and lateralization of the tibial tuberosity and the patella. Purpose/Hypothesis: The purpose of the study was to identify any changes in the stress distribution of subchondral bone density across the patellofemoral (PF) joint before and after OWHTO through the use of computed tomography (CT) osteoabsorptiometry. We hypothesized that OWHTO would alter the distribution of contact stress in the PF joint. Study Design: Case series; Level of evidence, 4. Methods: A total of 17 patients (17 knees) who underwent OWHTO were enrolled in this study between September 2013 and September 2015. All patients underwent radiologic examination preoperatively and at 1 year postoperatively, and the distribution patterns of subchondral bone density through the articular surface of the femoral trochlea and patella were assessed preoperatively and >1 year postoperatively using CT osteoabsorptiometry. The quantitative analysis of the obtained mapping data focused on location of the high-density area (HDA) through the articular surface of the PF joint. The percentage of HDA at each divided region of the articular surface of the femoral trochlea and the patella was calculated. Results: In the radiologic evaluation, the Blackburne-Peel ratio was significantly reduced ( P < .001) after surgery, and the tilting angle of the patella was significantly decreased ( P < .001). On CT evaluation, the percentage of HDA in the lateral notch and lateral trochlea of the femur and in the medial portion of the lateral facet of the patella increased significantly after OWHTO surgery ( P ≤ .038). Conclusion: OWHTO significantly increased the stress distribution pattern of the lateral trochlea of the femur and the medial portion of the lateral facet of the patella. The procedure significantly lowered the patellar height and significantly decreased the patellar tilting angle after surgery.

Background: Post-arthroscopic osteonecrosis of the knee (PAONK) is a rare disorder condition. In addition, no studies have analyzed the relationship between the meniscus extrusion and PAONK. The purposes of this retrospective study are to report 10 cases of PAONK and to evaluate location of the MM in the joint space, including the meniscus extrusion, before and after the meniscectomy in these 10 knees. Methods: Ten knees with PAONK were found in 876 knees which had undergone arthroscopic partial meniscectomy of the medial meniscus (MM). We retrospectively collected the clinical, surgical, and radiological data of these 10 patients. To evaluate intraarticular location of the menisci in the joint space, Extrusion width and Inner width were defined on magnetic resonance images, and they were statistically compared. Results: In the 10 patients (2 men and 8 women; the age ranged between 60 and 80 years), knee pain recurred within 12 weeks after the meniscectomy. Preoperatively, the Extrusion width of the MM (the mean, 4.7 mm) was significantly greater (PConclusion: This is the first report that, in each of the 10 knees with PAONK, the MM had been extruded before the meniscectomy, and then, the Inner width of the MM almost disappeared postoperatively due to not only the increased meniscal extrusion but the partial meniscal resection. This study suggested that the intraarticular abnormal location of the MM, including the meniscal extrusion, is a critical factor that should be evaluated in future studies to clarify causative factors of PAONK.

Currently, various studies have been reported to regenerate the meniscus tissue in a large defect after partial meniscectomy using biological or synthetic scaffolds with or without fibrochondrocytes. However, the clinical utility of those treatments has not been established as of yet.Purposes of this study were to develop a sheep model to evaluate feasibility of this new surgical strategy to treat the irreparable meniscus injury, and to test the hypothesis that implantation of autogenous meniscal fragments wrapped with a fascia sheath may significantly induce fibrocartilage regeneration in a large meniscal defect in the sheep model.Twenty Suffolk sheep were used. In each animal, an anterior 10-mm width of the right medial meniscus was resected. Then, the animals were divided into the following 2 groups. In Group I, the defect was enveloped with a fascia from the left thigh. In Group II, the resected meniscus fragmented into small pieces was grafted into the defect. Then the defect was enveloped with a fascia. In each group, 5 of 10 sheep were used for histological and biomechanical evaluations, respectively, at 12 weeks after surgery.In Group I, the defect was incompletely filled with thin fibrous tissues, while fibrocartilage tissues rarely regenerated in the tissue. In Group II, all defects were completely filled with thick fibrocartilage tissues, which were richly stained with the safranin O staining. Both the gross and histological observation score of Group II was significantly (p=0.0005, p=0.0005) greater than that of Group I. Concerning the cross-sectional area of the regenerated tissue, Group II was significantly (p=0.0002) greater than Group I. In the biomechanical evaluation, the maximal load and the linear stiffness of the meniscus-tibia complex were significantly (p=0.0015, p=0.0283) greater in Group II than in Group I.Implantation of autogenous meniscal fragments wrapped with a fascia sheath significantly induces fibrocartilage regeneration into a large meniscal defect in the sheep model.Not applicable; Controlled Laboratory Study, Experimental in vivo study.

Background:Outcomes and complications at mid- or long-term follow-up after medial open-wedge high tibial osteotomy (MOWHTO) with the TomoFix locking plate have not been fully evaluated.Purpose:To evaluate the complications and midterm clinical outcomes after MOWHTO using a TomoFix.Study Design:Case series; Level of evidence, 4.Methods:Enrolled in this study were 80 patients (85 knees) who underwent MOWHTO with the TomoFix locking plate between 2009 and 2013. There were 66 women and 14 men, with a mean age of 61.5 years at the time of surgery. The diagnosis was medial osteoarthritis in 76 knees and spontaneous osteonecrosis of the knee in 9 knees. Metal removal and second-look arthroscopy were performed in all cases. Clinical and radiological examinations were performed at final follow-up after surgery (mean, 4.5 years).Results:The mean Japanese Orthopaedic Association score and Knee injury and Osteoarthritis Outcome Score improved significantly from pre- to postoperatively ( P < .0001). The weightbearing line percentage shifted to pass through a point 67.7% lateral from the medial edge of the tibial plateau. The Caton-Deschamps index changed significantly from 0.88 to 0.66 at final follow-up ( P < .0001). The mean posterior tibial slope changed significantly from 8.9° to 11.9° at final follow-up ( P < .0001). Limb length was significantly increased after MOWHTO (10.3 mm; P < .0001). During plate removal, 14 locking screws were found to be broken in 9 knees (10.6%). The articular cartilage grade of the patellofemoral joint was significantly higher in the second arthroscopy than in the first arthroscopy ( P < .0001). The cumulative rate of all complications was 41.2%, with major complications (ie, those requiring additional or extended treatment) in 24.7%.Conclusion:Postoperative outcome scores indicated significant improvement after MOWHTO, although the cumulative rate of all complications was 41.2% and the rate of major complications was 24.7%. These results indicate that MOWHTO with the TomoFix is a technically demanding procedure. Careful preoperative planning and meticulous surgical technique are needed to decrease the incidence of complications associated with MOWHTO.

Objective The impact of early resumption of oral intake after cardiac surgery on hemodynamics has not been characterized. The authors examined the effects of early oral intake on the oxygen supply-demand relationship in patients undergoing on-pump cardiac surgery in an early recovery after surgery program. Design Prospective data were collected in postcardiac surgical patients in a multidisciplinary intensive care unit (ICU) during an 18-month period. Setting Single institution study. Participants Forty-three patients who underwent either mitral or aortic valve repair and were successfully liberated from ventilatory support within 10 hours after surgery. Interventions Patients were either allowed to resume oral intake on the morning of the first postoperative day or not at the discretion of the surgical team after extubation. Measurements and Main Results The oxygen supply-demand relationship was assessed continuously with cardiac index and mixed venous oxygen saturation (SvO2). Among the subjects, 22 patients were allowed to eat, and transient SvO2 decrease was noted in 13 patients. All transient SvO2 decreases occurred in the patients with early oral intake. The hemodynamic status and oxygen supply-demand relationship did not differ between the patients with and without transient SvO2 decrease. All the subjects were discharged successfully from the ICU on the first postoperative day, and the length of hospital stay was similar irrespective of SvO2 decrease after early oral intake. Conclusions Early oral intake shortly after extubation was associated with transient but significant SvO2 decrease in patients who underwent fast-track recovery after open-heart surgery. Because this phenomenon did not negatively affect the postoperative outcome, early oral intake may not be harmful.

The purpose of this description is to report an "acute oblique osteotomy and ligation" (AOOL) procedure to shorten the fibula in high tibial osteotomy (HTO). A 4-cm longitudinal skin incision is made at the lateral aspect of the leg. After the central portion of the fibula is circumferentially isolated from all the periosteal tissues, a simple osteotomy is performed at the mid-portion of the fibular diaphysis in the quasi-frontal plane, which is inclined by 25 to 30° to the long axis of the fibula. Two thin holes are created beside the osteotomy line on the lateral surface of the fibula. A polyester thread is passed through the 2 holes. After the HTO is completed, the surgeon easily reduces the displaced fibular ends using this thread. This thread is securely tied to keep the contact between the 2 osteotomized surfaces. The AOOL procedure is technically easy and safely performed. We believe that the AOOL procedure is clinically useful to shorten the fibular shaft in HTO.

Background:Remnant tissue preservation may be important in improving graft healing after anterior cruciate ligament (ACL) reconstruction, but it has yet to be established whether remnant tissue preservation improves the control of pivot-shift laxity.Hypothesis:The amount of ACL graft coverage with preserved remnant tissue improves the control of pivot-shift laxity, as qualitatively determined with an electromagnetic device.Study Design:Cohort study; Level of evidence, 3.Methods:The 3-dimensional kinematics were evaluated intraoperatively using an electromagnetic sensor system in 38 patients at the time of anatomic double-bundle ACL reconstruction with remnant tissue preservation and again at a minimum of 12 months postoperatively. The magnitude of the peak coupled anterior tibial translation (pCAT) and the maximal acceleration of posterior translation (APT) during the pivot-shift test were evaluated. The degree of graft coverage by remnant tissue was determined arthroscopically at the end of surgery, which was evaluated quantitatively using a scoring system (0-9 points). The relationship between the values during the pivot-shift test and preoperative and intraoperative factors were assessed.Results:The mean (±SD) side-to-side difference of the pCAT (ΔpCAT) was significantly ( P < .0001) improved from 14.0 ± 5.0 mm to 2.6 ± 1.1 mm. Also, the mean side-to-side difference of the APT (ΔAPT) was significantly ( P < .0001) improved from 525.6 ± 99.7 mm/s2to 32.9 ± 23.6 mm/s2. The mean initial graft coverage score was 5.3 ± 2.6. The correlation analysis demonstrated that the degree of initial graft coverage was significantly correlated with the ΔpCAT ( r = −0.517, P = .0007) and ΔAPT ( r = −0.532, P = .0005). The status of the reconstructed graft at second-look arthroscopic surgery showed no significant correlations with the degree of initial graft coverage or the results of the pivot-shift test.Conclusion:The present study demonstrated that the preservation of ACL remnant tissue in anatomic double-bundle ACL reconstruction appears to improve the control of pivot-shift laxity at a minimum of 12 months postoperatively, as measured by an electromagnetic device. This improvement was significantly affected by the degree of intraoperative graft coverage with preserved remnant tissue.

BackgroundTo perform medial open-wedge high tibial osteotomy (OWHTO), surgeons expose the medial-proximal tibia by releasing or cutting the superficial layer of the medial collateral ligament (sMCL). Biomechanically, the sMCL provides primary restraint against valgus forces. Therefore, any release of the sMCL can cause valgus instability of the knee joint. The purpose of this study was to assess valgus laxity after release of the medial structure of the knee during OWHTO.MethodsBetween 2009 and 2015, 84 consecutive patients (93 knees) who underwent OWHTO using a locking plate were enrolled in this study. All patients underwent radiological examinations before surgery, during surgery, 1 year after surgery, and after plate removal to objectively assess valgus laxity. The medial joint space (MJS) and the joint line convergence angle (JLCA) of the knee were evaluated using quantitative valgus stress radiography. Clinical evaluation was performed 2 years after surgery.ResultsThe mean functional knee score improved significantly, from 65.5 to 91.1 points (p p ConclusionValgus laxity was significantly greater after release of the sMCL. However, no significant differences were noted in valgus laxity in preoperative, 1-year postoperative periods and after plate removal. Complete release of the sMCL did not cause postoperative valgus laxity after OWHTO surgery.Trial registrationTrial registration number: No.012–0360.

A heating ventilation and air conditioning (HVAC) unit is an essential unit to adjust temperature for passenger’s comfortability in an automotive cabin. For efficient and reliable design and development of the HVAC unit, the interior thermal flow needs to be simulated and the performance needs to be evaluated with low cost and high fidelity. Hence, this paper develops measurement-based strategies for high-fidelity thermo-fluid dynamics simulation of an HVAC heat exchanger. These strategies tune up the parameters of a porous media model in the governing equations, which model the interaction between the heat exchanger and the surrounding thermal flow field and are conventionally fixed to certain constants, by functionalization or data assimilation with actual measurement data. The present results show that both strategies are able to reduce discrepancies between the simulation and the actual measurements, and improve fidelity to simulate the temperature field without sacrificing the simulation cost very much. Especially, the data assimilation strategy is more effective to yield more accurate simulation results only with the measurement data while the functionalization strategy needs to derive theoretical correlations. It demonstrates that data assimilation is helpful to assist reliable and efficient design and development of an HVAC unit regardless of designer’s professional skills or knowledge.

The microminipig is one of the smallest minipigs that has emerged as a possible experimental animal model, because it shares many anatomical and/or physiological similarities with humans, including the coronary artery distribution in the heart, the digestive physiology, the kidney size and its structure, and so on. However, information on gene expression profiles, including those on drug-metabolizing phase I and II enzymes, in the microminipig is limited. Therefore, the aim of the present study was to identify transcripts in microminipig livers and to determine gene expression profiles. De novo assembly and expression analyses of microminipig transcripts were conducted with liver samples from three male and three female microminipigs using parallel long-read and short-read sequencing technologies. After unique sequences had been automatically aligned by assembling software, the mean contig length of 50843 transcripts was 707 bp. The expression profiles of cytochrome P450 (P450) 1A2, 2C, 2E1 and 3A genes in livers in microminipigs were similar to those in humans. Liver carboxylesterase (CES) precursor, liver CES-like, UDP-glucuronosyltransferase (UGT) 2C1-like, amine sulfotransferase (SULT)-like, N-acetyltransferases (NAT8) and glutathione S-transferase (GST) A2 genes, which are relatively unknown genes in pigs and/or humans, were expressed strongly. Furthermore, no significant gender differences were observed in the gene expression profiles of phase I enzymes, whereas UGT2B17, SULT1E1, SULT2A1, amine SULT-like, NAT8 and GSTT4 genes were different between males and females among phase II enzyme genes under the present sample conditions. These results provide a foundation for mechanistic studies and the use of microminipigs as model animals for drug development in the future. Copyright © 2016 John Wiley & Sons, Ltd.

Background: To date, no studies have analyzed the influence on clinical outcomes of the interval between an anterior cruciate ligament (ACL) injury and double-bundle (DB) reconstruction with hamstring tendon autografts. Hypotheses: (1) Performing ACL reconstruction sooner after an injury will reduce postoperative anterior and rotatory knee instability, (2) postoperative range of knee motion or functional results will not be affected by different intervals between injury and surgery, and (3) preoperative isokinetic peak torque of the quadriceps and hamstring muscles will be lower in patients undergoing surgery earlier, while postoperative muscle strength will not be affected by surgery timing. Study Design: Cohort study; Level of evidence, 3. Methods: This study was conducted on a total of 171 patients who had undergone anatomic DB ACL reconstruction with hamstring tendon autografts. The patients were divided into 3 groups based on the time to surgery: (1) ≤1 month after the injury (group E; n = 25), (2) between 1 and 3 months after the injury (group M; n = 72), and (3) >3 months after the injury (group D; n = 74). Patients were assessed for a minimum of 2 years after surgery. Results: Concerning postoperative anterior laxity, 1-way analysis of variance demonstrated a significant difference ( P = .0274) among the 3 groups. Anterior laxity was significantly less in group E than in group D ( P = .0206). Spearman rank correlation analysis showed a significant correlation (ρ = 0.200; P = .0327) between anterior knee laxity and time to surgery. Also, a significant correlation ( P = .0461) was found between the degree of the pivot-shift phenomenon and time to surgery. There were no significant differences in loss of knee extension or flexion among the 3 groups, nor were there any differences in the Lysholm knee score or International Knee Documentation Committee grade. Postoperatively, there were no significant differences in peak torque of the quadriceps or hamstring muscles among the 3 groups. Conclusion: Early DB reconstruction led to significantly less anterior laxity compared with delayed reconstruction. There were no significant differences in postoperative range of knee motion or functional results among the 3 time intervals between injury and surgery in this study.

Oncogene addiction can provide therapeutic opportunities in human malignancies. In this study, we aimed to identify critical oncogenes for oral squamous cell carcinoma (OSCC) development and progression. We determined gene expression profiles in 10 primary OSCCs and 10 human OSCC cell lines using Applied Biosystems Human Genome Survey Arrays. Akt1 was the only gene identified that was expressed in all OSCC tissues and cultured cells, but not in non-neoplastic tissues and cells. Subsequently, western blot analysis showed that Akt1 protein was overexpressed in OSCC tissues and cell lines. Immunohistochemistry also showed Akt1 protein expression in 59 of 63 (94%) primary OSCCs. To clarify the oncogenic function of Akt1 in human OSCC cells, we used RNA interference. We designed and synthesized 5 small interfering RNAs specific for Akt1 (siAkt1). Transfecting human OSCC cells with siAkt1 in vitro markedly suppressed their expression of Akt1 protein and significantly reduced their growth rate. Furthermore, the growth of human OSCC tumors which had been subcutaneously xenografted in athymic nude mice lacking interferon responses was markedly inhibited by atelocollagen-mediated systemic siAkt1 administration. We also found that synthetic siAkt1 had an inhibitory effect on the growth of primary cultured OSCC cells. Finally, we investigated the molecular mechanisms involved in the growth inhibitory effect of Akt1 suppression using microarray analysis of human OSCC cells transfected with siAkt1. Knockdown of Akt1 induced the expression of CDKN2B, a tumor suppressor gene, and reduced the expression of TGFBR1, which supports malignant phenotypes. These results suggest that Akt1 functions as a critical oncogene in human OSCC cells and may therefore be an appropriate target for novel OSCC therapies.

To assess food safety emergencies caused by highly hazardous chemical-tainted foods, simultaneous analysis of organophosphorus insecticides in fatty foods such as precooked foods was conducted using thin-layer chromatography/direct analysis in real time time-of-flight mass spectrometry (TLC/DART-TOFMS) and isotope dilution technique. Polar (methamidophos and acephate) and nonpolar organophosphorus insecticides (fenitrothion, diazinon, and EPN) were studied. Experiments to ascertain chromatographic patterns using TLC/DART-TOFMS reveal that it was more useful than GC/MS or GC/MS/MS for the simultaneous analyses of polar and nonpolar pesticides, while obviating the addition of a protective agent for tailing effects of polar pesticides. Lower helium gas temperature (260 °C) for DART-TOFMS was suitable for the simultaneous analysis of target pesticides. Linearities were achieved respectively at a lower standard concentration range (0.05–5 μg) for diazinon and EPN and at a higher standard concentration range (2.5–25 μg) for methamidophos, acephate, and fenitrothion. Their respective coefficients of determination were ≥0.9989 and ≥0.9959. A few higher repeatabilities (RSDs) for diazinon and EPN were found (>20%), although isotope dilution technique was used. Application to the HPTLC plate without an automatic TLC sampler might be inferred as a cause of their higher RSDs. Detection limits were estimated in the higher picogram range for diazinon and EPN, and in the lower nanogram range for methamidophos, acephate, and fenitrothion. Aside from methamidophos, recovery results (n = 3) obtained using a highly insecticide-tainted fatty food (dumpling) and raw food (grapefruit) samples (10 mg/kg) using TLC/DART-TOFMS with both complex and simpler cleanups were not as susceptible to matrix effects (95–121%; RSD, 1.3–14%) as those using GC/MS/MS (102–117%; RSD, 0.4–8.5%), although dumpling samples using GC/MS were remarkably susceptible to matrix effects. The coupled method of TLC with simpler cleanup and DART-TOFMS can be regarded as the same analytical tool as GC/MS/MS, which is useful to assess food safety emergencies caused by highly hazardous chemical-tainted foods.

The purpose of this study was to clinically and radiologically compare the utility, osteoconductivity, and absorbability of hydroxyapatite (HAp) and beta-tricalcium phosphate (TCP) spacers in medial open-wedge high tibial osteotomy (HTO). Thirty-eight patients underwent medial open-wedge HTO with a locking plate. In the first 19 knees, a HAp spacer was implanted in the opening space (HAp group). In the remaining 19 knees, a TCP spacer was implanted in the same manner (TCP group). All patients underwent clinical and radiological examinations before surgery and at 18 months after surgery. Concerning the background factors, there were no statistical differences between the two groups. Post-operatively, the knee score significantly improved in each group. Concerning the post-operative knee alignment and clinical outcome, there was no statistical difference in each parameter between the two groups. Regarding the osteoconductivity, the modified van Hemert’s score of the TCP group was significantly higher (p = 0.0009) than that of the HAp group in the most medial osteotomy zone. The absorption rate was significantly greater in the TCP group than in the HAp group (p = 0.00039). The present study demonstrated that a TCP spacer was significantly superior to a HAp spacer concerning osteoconductivity and absorbability at 18 months after medial open-wedge HTO. Retrospective comparative study, Level III.

Background:The effects of remnant tissue preservation on tunnel enlargement after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction have not yet been established.Hypothesis:The preservation of ACL remnant tissue may significantly reduce the degree and incidence of tunnel enlargement after anatomic double-bundle ACL reconstruction, while the remnant-preserving procedure may not significantly increase the incidence of tunnel coalition after surgery.Study Design:Cohort study; Level of evidence, 2.Methods:A total of 79 patients underwent anatomic double-bundle ACL reconstruction. Based on the Crain classification of ACL remnant tissue, 40 patients underwent the remnant-preserving procedure (group P), and the remaining 39 patients underwent the remnant-resecting procedure (group R). There were no differences between the 2 groups concerning all background factors, including preoperative knee instability and intraoperative tunnel positions. All patients were examined using computed tomography and a standard physical examination at 2 weeks and 1 year after surgery.Results:During surgery, the femoral and tibial anteromedial (AM) tunnel sizes in both groups averaged 6.6 and 6.5 mm, respectively. The femoral and tibial posterolateral (PL) tunnel sizes in both groups averaged 6 and 6 mm, respectively. There were no differences in the intraoperative tunnel positions and tunnel sizes between groups. Concerning the femoral AM tunnel, the degree of tunnel enlargement in the oblique coronal and oblique axial views in group P was significantly less than that in group R ( P = .0068 and .0323, respectively). Regarding the femoral AM tunnel cross-sectional area, the degree and incidence of tunnel enlargement in group P were significantly less than those in group R ( P = .0086 and .0278, respectively). There were no significant differences in tunnel coalition between groups. In each group, there were no significant relationships between tunnel enlargement and each clinical outcome.Conclusion:Remnant preservation in anatomic double-bundle ACL reconstruction reduced enlargement of the femoral AM tunnel and did not increase the incidence of tunnel coalition. This is one of the advantages of remnant-preserving ACL reconstruction.

The data available from the previously reported clinical studies remains insufficient concerning the hamstring graft preparation in double-bundle anterior cruciate ligament (ACL) reconstruction.To test the hypothesis that there are no significant differences between the semitendinosus tendon alone and the semitendinosus and gracilis tendon graft fashioning techniques concerning knee stability and clinical outcome after anatomic double-bundle ACL reconstruction.A prospective study was performed on 120 patients who underwent anatomic double-bundle ACL reconstruction according to the graft fashioning technique. The authors developed the protocol to use hamstring tendon autografts. When the harvested doubled semitendinosus tendon is thicker than 6 mm, each half of the semitendinosus tendon is doubled and used for the anteromedial (AM) and posterolateral (PL) bundle grafts (Group I). On the other hand, when the harvested semitendinosus tendon is under 6 mm in thickness, the gracilis tendon is harvested additionally. The distal half of the semitendinosus and gracilis tendons are doubled and used for the AM bundle graft, and the remaining proximal half of the semitendinosus tendon is doubled and used for the PL bundle grafts (Group II). Sixty-one patients were included in Group I, and 59 patients in Group II. The two groups were compared concerning knee stability and clinical outcome 2 years after surgery.The postoperative side-to-side anterior laxity averaged 1.3 mm in both groups, showing no statistical difference. There were also no significant differences between the two groups concerning the peak isokinetic torque of the quadriceps and the hamstrings, the Lysholm knee score, and the International Knee Documentation Committee evaluation.There were no significant differences between the two graft fashioning techniques after anatomic double-bundle ACL reconstruction concerning knee stability and postoperative outcome. The present study provided orthopedic surgeons with important information on double-bundle ACL reconstruction with hamstring tendons.Level II; prospective comparative study.

OBJECTIVES Traumatized muscle is a complex healing environment containing cells with robust reparative and regenerative potential interacting in a cytokine milieu that influences the function and differentiation of these cells, leading to a spectrum of healing responses. In particular, bone morphogenetic protein-4 (BMP-4) is of interest as a potential modulator of healing because its dysregulation has been associated with fibrosis and heterotopic ossification formation. We propose a descriptive study of altered BMP-4 expression in traumatized muscle tissue and to evaluate its role in the fibroregulatory function of resident mesenchymal progenitor cells (MPCs) at the protein- and gene-expression levels. METHODS Protein-level expression of BMP-4 from cells resident in traumatized muscle specimens was evaluated using ELISA and also using sodium dodecyl sulfate-polyacrylamide gel electrophoresis to compare BMP-4 in homogenized muscle tissue specimens. BMP-4, cartilage oligomeric matrix protein (COMP), and osteocalcin expression localization was analyzed via immunohistochemistry. Reverse transcription-polymerase chain reaction was performed to evaluate fibroregulatory gene expression in MPCs after treatment with BMP-4. RESULTS BMP-4 was present in all traumatized muscle tissue specimens. Immunohistochemistry demonstrated that traumatized muscle fibers contained greater number of cells expressing BMP-4 in a more disorganized fashion compared with control samples. Reverse transcription-polymerase chain reaction demonstrated that COMP, growth and differentiation factor-10, and integrin beta-2 were up-regulated, whereas tumor necrosis factor-alpha was significantly down-regulated. COMP expression was colocalized in the traumatized muscle tissue with osteocalcin. CONCLUSIONS BMP-4 has an effect on MPCs that seems to promote fibrotic tissue formation. These findings suggest that BMP-4, while promoting osteoinduction, may also act on MPCs to promote formation of a fibrotic osteoinductive matrix. Thus, this signaling axis might be a potential target for heterotopic ossification prevention.

Background: In anatomic double-bundle anterior cruciate ligament (ACL) reconstruction, there are great controversies concerning the ideal graft tension protocols. The purpose of this study was to clarify differences in the effect of two graft tension protocols on the clinical outcome after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction by comparing the minimum 2-year clinical results. Methods: Ninety-seven patients with unilateral anatomic double-bundle ACL reconstruction were divided into two groups. In the first 44 patients (Group I), a 40-N tension was applied to each of the two hamstring autografts at 30 degrees of knee flexion, and simultaneously fixed onto the tibia. In the remaining 53 patients (Group II), a 30-N tension was applied to each graft at 10 degrees of knee flexion, and simultaneously fixed onto the tibia. Each patient was examined 2 years after surgery. Results: There wasn't a significant difference in the background of the two groups. There was no significant difference in the postoperative anterior laxity between the two groups. The average was 1.1 mm and 0.9 mm in Groups I and II, respectively. There wasn't any differences between the two groups in Lysholm knee score, International Knee Documentation Committee (IKDC) evaluation and muscle strength. Four patients had loss of knee extension in a range of 5 degrees and 10 degrees in Group I and none of the patients in Group II exhibited any loss in knee extension; which was statistically significant (p = 0.025). Conclusion: The two initial graft tension protocols did not result in any significant differences in the Lysholm knee score and IKDC grade. However, it was noted that the 40-N tension applied to each graft at 30 degrees of knee flexion more significantly induced loss of knee extension in comparison to the 30-N tension applied to each graft at 10 degrees. From a clinical viewpoint, the loss of knee extension is one of the pathological conditions that should be absolutely avoided after ACL reconstruction. Therefore, the 30-N tension applied to each graft at 10 degrees is preferable to the other graft tension protocol.

In order to establish the convertibility of a host for bone augmentation, we herein developed a new honeycombshaped β-tricalcium phosphate (37H) using atelocollagen as a scaffold, which exhibited unique geometric properties for in vitro and in vivo studies. Human mesenchymal stem cells (MSC) were cultured with 37H or atelocollagen-coated honeycomb-shaped β-tricalcium phosphate (Col37H), and their osteoblastic differentiation was then analyzed. Atelocollagen promoted cell adhesion and formation of vessel-like structures in the tunnels of scaffolds of cultured MSC. The mRNA expression levels of type I collagen, osteocalcin, and VEGF were greater in MSC cultured with Col37H than with 37H. Bone generation with Col37H in the rat calvaria was greater than with 37H, and this was attributed to early vessel construction. A large number of blood vessels invaded tunnels from the periosteum and existing bone surface. A strong VEGF signal was detected immediately before the new bone surface in the tunnels of Col37H. These results indicate that the addition of atelocollagen to Col37H has potential in the construction of functional artificial bone.

The microminipig is one of the smallest minipigs that has emerged as a possible experimental animal model, because it shares many anatomical and/or physiological similarities with humans, including the coronary artery distribution in the heart, the digestive physiology, the kidney size and its structure, and so on. However, information on gene expression profiles, including those on drug-metabolizing phase I and II enzymes, in the microminipig is limited. Therefore, the aim of the present study was to identify transcripts in microminipig livers and to determine gene expression profiles. De novo assembly and expression analyses of microminipig transcripts were conducted with liver samples from three male and three female microminipigs using parallel long-read and short-read sequencing technologies. After unique sequences had been automatically aligned by assembling software, the mean contig length of 50843 transcripts was 707 bp. The expression profiles of cytochrome P450 (P450) 1A2, 2C, 2E1 and 3A genes in livers in microminipigs were similar to those in humans. Liver carboxylesterase (CES) precursor, liver CES-like, UDP-glucuronosyltransferase (UGT) 2C1-like, amine sulfotransferase (SULT)-like, N-acetyltransferases (NAT8) and glutathione S-transferase (GST) A2 genes, which are relatively unknown genes in pigs and/or humans, were expressed strongly. Furthermore, no significant gender differences were observed in the gene expression profiles of phase I enzymes, whereas UGT2B17, SULT1E1, SULT2A1, amine SULT-like, NAT8 and GSTT4 genes were different between males and females among phase II enzyme genes under the present sample conditions. These results provide a foundation for mechanistic studies and the use of microminipigs as model animals for drug development in the future. Copyright © 2016 John WileySons, Ltd.

Background: Several recent studies have reported that favorable clinical results and a high level of patient satisfaction can generally be obtained with no increased risk of complications after single-bundle anterior cruciate ligament (ACL) reconstruction performed in patients >40 years of age. However, no studies have yet clarified the age-based differences in clinical outcomes after double-bundle reconstruction. Purpose: To compare clinical outcomes after double-bundle ACL reconstruction using hamstring tendon hybrid grafts between patients in 2 different age groups: ≥40 years and Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective study was conducted using 96 patients (48 men, 48 women ; mean age, 37 years) who underwent unilateral ACL reconstruction between 2008 and 2011. These patients were divided into 2 groups: group M included patients ≥40 years of age (n = 40 patients), and group Y included patients Results: Mean postoperative side-to-side differences in anterior laxity were 0.5 ± 1.9 mm and 1.2 ± 1.5 mm in groups M and Y, respectively; there was a significant difference between the 2 groups ( P = .039). There were no significant differences between the groups in Lysholm knee scores, International Knee Documentation Committee (IKDC) scores, or peak muscle torque of the hamstring. On the other hand, peak muscle torque of the quadriceps was significantly lower in group M (81%) than in group Y (89%) ( P = .025). With respect to femoral tunnel enlargement, the posterolateral tunnel in group M was significantly larger than that in group Y on anteroposterior and lateral radiographs ( P = .015 and P = .002, respectively). Conclusion: Equivalent clinical outcomes were seen between the 2 age groups after double-bundle ACL reconstruction. Postoperative anterior laxity was significantly less in older patients than in younger patients, however, older patients had significantly less quadriceps muscle strength than younger patients. Surgeons should be aware of residual muscle weakness and tunnel enlargement when performing double-bundle ACL reconstruction in older patients.

Early phase prostate cancer is usually androgen-dependent, with the androgen/androgen receptor (AR) signaling pathway playing a central role. At this stage, the cancer responds well to androgen ablation therapy, but prostate cancers eventually acquire androgen independence and more aggressive phenotypes. Several studies, however, have shown that the majority of tumors still express functional AR, which is often amplified and mutated. To determine if the AR is a plausible therapeutic target, we investigated the anti-tumor effect of small interfering RNAs targeting the AR (siAR) in the human prostate cancer cells, LNCaP and 22Rv1, which express mutated AR. In both types of cells, transfection of siAR suppressed mutated AR expression and significantly reduced cell growth. Furthermore, atelocollagen-mediated systemic siAR administration markedly inhibited the growth of 22Rv1 cells subcutaneously xenografted in castrated nude mice. These results suggest that the AR is still a key therapeutic target even in androgen-independent prostate cancer (AIPC). Silencing of AR expression in AIPC opens promising therapeutic perspectives.

Background: Clinical utility of remnant tissue preservation after single-bundle anterior cruciate ligament (ACL) reconstruction has not been established. In addition, no studies have evaluated the clinical utility of remnant preservation after anatomic double-bundle ACL reconstruction. Hypothesis: The study hypotheses were as follows: (1) Subjective and functional clinical results may be comparable between anatomic double-bundle reconstructions that preserve the remnant tissue and those that resect the remnant tissue, (2) postoperative knee stability and the second-look arthroscopic evaluation may be significantly more favorable with the remnant-preserving reconstruction, and (3) the degree of the initial graft coverage may significantly affect postoperative knee stability. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 179 patients underwent anatomic double-bundle ACL reconstruction. Based on the Crain classification of ACL remnant tissue, 81 patients underwent the remnant-preserving procedure (group P) and the remaining 98 patients underwent the remnant-resecting procedure (group R). There were no differences between the 2 groups concerning all background factors, including preoperative knee instability and intraoperative tunnel positions. The patients were followed for 2 years or more. Results: The subjective and functional clinical results were comparable between the 2 reconstruction procedures. Side-to-side anterior laxity was significantly less ( P = .0277) in group P (0.9 mm) than in group R (1.5 mm). The pivot-shift test was negative in 89% of group P and 78% of group R patients; the result for group R was significantly lower ( P = .0460). In the arthroscopic observations, results for group P were significantly better than for group R concerning postoperative laceration and fibrous tissue coverage of the grafts ( P = .0479). Conclusion: Remnant preservation in anatomic double-bundle ACL reconstruction did not significantly improve subjective and functional results in the short-term evaluation, but it significantly improved postoperative knee stability. The degree of initial graft coverage significantly affected postoperative knee stability.

We discuss switching behavior of superjunction (SJ)-MOSFETs in terms of interaction between MOS gate structure and charge imbalance (CIB) of SJ structure. Resistive load switching behavior of SJ-MOSFET was analyzed by device simulation. CIB changes the gate voltage transient behavior between gate threshold voltage and gate plateau voltage via modification of the potential near the gate. We found key parameter which determines the effect of MOS structure and layout upon loss, and indicated robust MOS gate design and layout from the perspective of switching loss. Finally, we confirmed the conclusion by experiment.

Plastocyanin was purified from the gymnosperm Ginkgo biloba L., and its complete amino acid sequence was determined. The protein was shown to contain Phe-83 instead of Tyr-83 conserved in other land plant plastocyanins. This is the first report of the characterization and complete amino acid sequence of a gymnosperm plastocyanin.

Autophagy is a transport system of cytoplasmic components to the lysosome/vacuole for degradation well conserved in eukaryotes. Autophagy is strongly induced by nutrient starvation. Several specific proteins, including amino acid synthesis enzymes and vacuolar enzymes, are increased during nitrogen starvation in wild-type cells but not in autophagy-defective delta atg7 cells despite similar mRNA levels. We further examined deficiencies in these cells. Bulk protein synthesis was substantially reduced in delta atg7 cells under nitrogen starvation compared with wild-type cells. The total intracellular amino acid pool was reduced in delta atg7 cells, and the levels of several amino acids fell below critical values. In contrast, wild-type cells maintained amino acid levels compatible with life. Autophagy-defective cells fail to maintain physiologic amino acid levels, and their inability to synthesize new proteins may explain most phenotypes associated with autophagy mutants at least partly.