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We recently reported that skin vasoconstriction to suppress transepidermal water loss (TEWL) leads to hypertension in renal injury model rats with impaired urine concentration ability. In this study, we investigated the pathogenesis of hypertension in spontaneously hypertensive rats (SHRs) from the perspective of renal water loss and skin water conservation. We compared the urinary concentration ability, body sodium and water balance, blood pressure, and TEWL in SHRs and control normotensive Wistar-Kyoto rats (WKYs). SHRs showed significantly higher urine volume and lower urinary osmolality than those of WKYs, while there were no significant differences in water intake, urinary osmolyte excretion, and plasma osmolarity between the groups. SHRs exhibited significantly higher blood pressure, skin sodium content, and lower TEWL compared with those is WKYs. Skin vasodilation, induced by elevating body temperature, increased TEWL in both SHRs and WKYs, and significantly reduced blood pressure in SHRs but not WKYs. These findings suggest that physiological adaptation can reduce dermal water loss in SHRs to compensate for renal water loss. Vasoconstriction required for successful cutaneous water conservation explains SHR hypertension. Renal concentration ability and skin barrier function for water conservation may become a novel therapeutic target for essential hypertension.

The primary purpose of this study was to evaluate the second-look arthroscopic findings 1 year postoperatively and magnetic resonance imaging (MRI) findings 2 years after anterior cruciate ligament reconstruction (ACLR) using bone-patellar tendon–bone autograft (BTB) or hamstring tendon autograft (HT). Secondary purpose included clinical results from physical examination, including range of motion, Lachman test, pivot shift test, and knee anterior laxity evaluation, and the clinical score for subjective evaluations at 2 years after surgery. Between 2015 and 2018, 75 patients with primary ACL injuries were divided into either the BTB group (n = 30) or HT group (n = 45). When using HT, an anatomical double-bundle ACLR was performed. BTB was indicated for athletes with sufficient motivation to return to sporting activity. Graft maturation on second-look arthroscopy was scored in terms of synovial coverage and revascularization. All participants underwent postoperative MRI evaluation 2 years postoperatively. The signal intensity (SI) characteristics of the reconstructed graft were evaluated using oblique axial proton density-weighted MR imaging (PDWI) perpendicular to the grafts. The signal/noise quotient (SNQ) was calculated to quantitatively determine the normalized SI. For clinical evaluation, the Lachman test, pivot shift test, KT-2000 evaluation, Lysholm score, and Knee injury and Osteoarthritis Outcome Score (KOOS) were used. Arthroscopic findings showed that the graft maturation score in the BTB group (3.6 ± 0.7) was significantly greater than that in the anteromedial bundle (AMB; 2.9 ± 0.2, p = 0.02) and posterolateral bundle (PLB; 2.0 ± 0.9, p = 0.001) in the HT group. The mean MRI-SNQs were as follows: BTB, 2.3 ± 0.5; AMB, 2.9 ± 0.9; and PLB, 4.1 ± 1.1. There were significant differences between BTB, AMB, and PLB (BTB and AMB: p = 0.04, BTB and PLB: p = 0.003, AMB and PLB: p = 0.03). Second-look arthroscopic maturation score and MRI-SNQ value significantly correlated for BTB, AMB, and PLB. No significant differences were detected in clinical scores. There was a significant difference (p = 0.02) in the knee laxity evaluation (BTB: 0.9 ± 1.1 mm; HT: 2.0 ± 1.9 mm). BTB maturation is superior to that of double-bundle HT based on morphological and MRI evaluations following anatomical ACLR, although no significant differences were found in clinical scores. Regarding clinical relevance, the advantages of BTB may help clinicians decide on using the autograft option for athletes with higher motivation to return to sporting activity because significant differences were observed in morphological evaluation, MRI assessment, and knee anterior laxity evaluation between BTB and double-bundle HT. Level IV.

This study aimed to assess the risk factors for prolonged joint effusion in patients undergoing double-bundle anterior cruciate ligament reconstruction (ACLR). In total, 160 patients who underwent primary ACLR using autograft hamstring between 2015 and 2018 were retrospectively reviewed. Joint effusion was defined as any grade ≥ 2 (range, 0–3) according to the MRI Osteoarthritis Knee Score (MOAKS). Univariate and multivariate logistic regression analyses were performed. The median age of the patients was 25 years (range 14–68 years) at the time of the surgery; there were 89 women and 71 men. At 1 year, 46 (28.8%) patients experienced knee joint effusion, as defined by the MOAKS. Univariate analysis revealed that age, preoperative Kellgren–Lawrence (K–L) grade, and joint effusion at 6 months were significantly associated with joint effusion at 1 year. In the multivariate analysis, joint effusion at 6 months was significantly associated with joint effusion at 1 year (odds ratio, 68.0; 95% confidence interval, 22.1–209.4). No significant difference in the Lysholm scores was observed between patients with and without joint effusion at 1 year (n.s.). Joint effusion at 6 months was significantly associated with joint effusion 1 year after ACLR. III.

Objectives To assess the impact of a biplanar ascending opening-wedge high tibial osteotomy (OWHTO) on the alignment of the knee extensor mechanism and patellar height using preoperative and postoperative MRI. Methods Medical records of all patients submitted to ascending biplanar OWHTO between July 2008 and March 2017 were retrospectively assessed. Five parameters of the patellofemoral joint—tibial tubercle–trochlear groove distance (TT-TG), patellofemoral (PF) axial engagement index, lateral patellar tilt, Blackburne-Peel index (BPI) and Caton-Deschamps index (CDI)—were measured by two blinded independent observers on both preoperative and postoperative MRIs. Interobserver reliability was assessed with the intraclass correlation coefficient (ICC). Paired t-test was performed to compare preoperative and postoperative measurements. The association of the amount of HTO opening and the assessed PF joint parameters was also investigated with Pearson correlation coefficient. Results 26 patients who underwent ascending biplanar OWHTO were enrolled in this imaging analysis (63.4%) with a mean follow-up of 16.3 months (SD, 16.9). ICC for all measurements ranged between 73.3% and 89.3%. Postoperatively, TT-TG distance significantly increased by 2.0 mm±2.3 mm (p Conclusion This study comprehensively reports significant increase on TT-TG distance after an ascending biplanar OWHTO using MRI. Small but significant decreases in patellar height were also observed and are correlated to the amount of axis correction. Level of evidence Level IV, retrospective case study.

Background:Autologous chondrocyte implantation (ACI) provides a successful outcome for treating articular cartilage lesions. However, there have been very few reports on the clinical outcomes of revision ACI for failed ACI.Purpose:To evaluate clinical outcomes in patients who underwent revision ACI of the knee for failure of an initial ACI and to determine the factors affecting the survival rate.Study Design:Case series; Level of evidence, 4.Methods:A review of a prospectively collected data set was performed from patients who underwent revision ACI of the knee for failure of an initial ACI between 1995 and 2014 by a single surgeon. The authors evaluated 53 patients (53 knees; mean age, 38 years) over a mean 11.2-year follow-up (range, 2-20). A total of 62 cartilage lesions were treated for failed graft lesions after an initial ACI, and 31 new cartilage lesions were treated at revision ACI, as there was progression of disease. Overall, 93 cartilage lesions (mean, 1.8 lesions per knee) with a total surface area of 7.4 cm2(range, 2.5-18 cm2) per knee were treated at revision ACI. Survival analysis was performed with the Kaplan-Meier method, with ACI graft failure or conversion to a prosthetic arthroplasty as the endpoint. The modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, and 36-Item Short Form Health Survey were used to evaluate clinical outcomes. Patients also self-reported knee function and satisfaction. Standard radiographs were evaluated with Kellgren-Lawrence grades.Results:Survival rates were 71% and 53% at 5 and 10 years, respectively. Survival subanalysis revealed a trend that patients without previous cartilage repair procedures before an initial ACI had better survival rates than those with such procedures (81% vs 62% at 5 years, 64% vs 42% at 10 years, P = .0958). Patients with retained grafts showed significant improvement in pain and function, with a high level of satisfaction. At a mean 5.1 years postoperatively, 18 of 27 successful knees were radiographically assessed with no significant osteoarthritis progression. Outcomes for 26 patients were considered failures (mean, 4.9 years postoperatively), in which 15 patients had prosthetic arthroplasty (mean, 4.6 years) and the other 11 patients had revision cartilage repair (mean, 5.4 years) and thus could maintain their native knees.Conclusion:Results of revision ACI for patients who failed ACI showed acceptable clinical outcomes. Revision ACI may be an option for young patients after failed initial ACI, particularly patients without previous cartilage repair procedures and those who desire to maintain their native knees.

Objective Autologous chondrocyte implantation was the first cell-based therapy that used a tissue engineering process to repair cartilage defects. Recently improved approaches and tissue-engineered cell constructs have been developed for growing patient populations. We developed a chondrocyte construct using a collagen gel and sponge scaffold and physicochemical stimuli, implanted with a surgical adhesive. We conducted a proof-of-concept study of these improvements using a cartilage defect model in miniature swine. Design We implanted the autologous chondrocyte constructs into full-thickness chondral defects in the femoral condyle, compared those results with empty and acellular scaffold controls, and compared implantation techniques with adhesive alone and with partial adhesive with suture. Two weeks after the creation of the defects and implantation of the cellular or acellular constructs, we arthroscopically confirmed that the implanted constructs remained at the chondral defects. We evaluated the regenerated tissue macro- and microscopically 6 months after the cell constructs were implanted. The tissues were stained with Safranin-O and evaluated using Sellers’ histology grading system. Results The defects implanted with processed cell constructs and acellular scaffolds were filled with chondrocyte-like round cells and with nearly normal tissue architecture that were significantly greater degree compared to empty defect control. Even with the adhesive alone and with suture alone, the cell construct was composed of the dense cartilaginous matrix that was found in the implantation using both the sutures and the adhesive. Conclusion Implantation of cell constructs promoted regeneration and integration of articular cartilage at chondral defects in swine by 6 months.

We show the design, fabrication, and characterization of a wedge-shape Au thin film for integrating multiple surface plasmon resonance transducers in a single chip, which enhances the figure-of-merit by the reflectivity change with an attenuated-total-reflection setup upon modulating the wavenumber of surface plasmon polariton with the thickness of Au.

In supply chains the collaboration between manufacturing companies is crucial to ensure resilient and efficient operation in the face of uncertainty. This is especially true for manufacturers with global supply chains in highly competitive markets with fluctuating demand. We develop a novel approach to sharing of manufacturing capacity in supply chains. The approach is based on combinatorial auctions in which suppliers and buyers submit bids for manufacturing capacity. We present the mixed integer programming formulation of the winner determination problem and evaluates the efficiency and complexity of the approach on several realistic instances. We find that the number of accepted bids increases up to 10-fold compared to a situation without capacity sharing.

Background: Autologous chondrocyte implantation (ACI) is a well-established cartilage repair procedure; however, numerous studies have shown higher ACI graft failure rates after prior marrow stimulation techniques (MSTs). Purpose: To identify which factors may predict decreased graft survival after ACI among patients who underwent a prior MST. A secondary aim was to investigate the specificity of these predictors. Study Design: Case-control study; Level of evidence, 3. Methods: In this review of prospectively collected data, the authors analyzed 38 patients who had failed prior MST surgery and subsequently underwent collagen-covered ACI (case group). The case group was divided into graft failure ACI (n = 8, 21%) and successful ACI (n = 30, 79%). Fourteen clinical variables were categorized and analyzed to determine predictors for failure of the ACI graft: age, body mass index, sex, defect characteristics (number, size, location, etiology, type), presence of kissing lesion, intraoperative presence of intralesional osteophyte, time between an MST and ACI, previous surgery, duration of the symptoms, and concomitant surgical procedure. Preoperative magnetic resonance imaging (MRI) was used to evaluate the severity of subchondral bone marrow edema (BME), graded I (absent) to IV (severe), and the presence of subchondral cyst, hypertrophic sclerosis, and intralesional osteophyte. The effects of these MRI findings on the graft survivor were also investigated. Concurrently, a control group without a prior MST was matched to investigate the specificity of the previously determined predictors. These patients were matched individually according to age, sex, body mass index, and outcome of the procedure (failure [n = 8] or successful [n = 30] per the case group). Results: In the case group, the presence of preoperative severe BME was significantly higher among patients with failed ACI as compared with patients with successful ACI ( P < .001). In the control group, the presence of severe BME was not significantly different between the failure and successful groups ( P = .747). The ACI graft failure rate among patients with a prior MST and preoperative grade IV BME was 83.7% at 5 years postoperatively, resulting in a significantly lower survival rate as compared with patients with a prior MST and without severe BME (5-year graft failure rate, 6.5%; P < .001). All the other parameters did not differ significantly. Conclusion: After a prior MST, the presence of grade IV BME by MRI was a predictive factor for graft failure among patients who then underwent second-generation ACI.

Irritant contact dermatitis (ICD) is one of the most common inflammatory skin diseases caused by exposure to chemical irritants. Since chemical irritants primarily damage keratinocytes, these cells play a pivotal role in ICD. One of the phosphoinositide-metabolizing enzymes, phospholipase C (PLC) δ1, is abundantly expressed in keratinocytes. However, the role of PLCδ1 in ICD remains to be clarified. Here, we found that croton oil (CrO)-induced ear swelling, a feature of ICD, was attenuated in keratinocyte-specific PLCδ1 knockout mice (PLCδ1 cKO mice). Dendritic epidermal T cells (DETCs), which have a protective role against ICD, were activated in the epidermis of the PLCδ1 cKO mice. In addition, the skin of CrO-treated PLCδ1 cKO mice showed increased infiltration of Gr1+CD11b+ myeloid cells. Of note, elimination of Gr1+CD11b+ myeloid cells restored CrO-induced ear swelling in PLCδ1 cKO mice to a similar level as that in control mice. Taken together, our results strongly suggest that epidermal loss of PLCδ1 protects mice from ICD through induction of Gr1+CD11b+ myeloid cells and activation of DETCs.

Objective Osteochondral allograft transplantation (OCA) is a well-established procedure for patients with symptomatic cartilage defects in the knee. Revision to OCA after prior failed cartilage repair has shown similar clinical outcomes as primary OCA; however, most of the failed procedures were arthroscopic procedures for smaller defects. There is no literature investigating the clinical outcomes after OCA for prior failed autologous chondrocyte implantation (ACI) for the treatment of large chondral defects of the knee. The purpose of this study was therefore to determine clinical outcomes of patients undergoing revision to OCA after prior failed ACI as compared with a matched cohort of patients undergoing OCA as a primary cartilage repair procedure (primary OCA). Design In this review of prospectively collected data, we analyzed data from 26 patients with at least 2 years follow-up. Thirteen patients who underwent revision to OCA after prior failed ACI by a single surgeon were compared with a matched group of patients who underwent primary OCA. The patients were matched per age, gender, body mass index, and defect size. Patient-reported outcomes, reoperations, and survival rates were compared between groups. Results There were no significant differences in patient-reported clinical outcome scores between the groups at final follow-up. Moreover, there was no significant difference in reoperation rates and survival rates between the groups. Conclusion The present study demonstrates that revision to OCA is a viable treatment option with favorable functional outcomes and similar reoperation and survival rate as primary OCA even for revision of large chondral defects previously treated with ACI.

Background:Treating bipolar chondral lesions in the patellofemoral (PF) compartment is a challenging problem. There are few reports available on the treatment of bipolar chondral lesions in the PF compartment.Purpose:To evaluate the clinical outcomes and graft survivorship after autologous chondrocyte implantation (ACI) for the treatment of bipolar chondral lesions in the PF compartment.Study Design:Case series; Level of evidence, 4.Methods:The authors evaluated 58 patients who had ACI by a single surgeon for the treatment of symptomatic bipolar chondral lesions in the PF compartment between November 1995 and June 2014. All 58 patients (60 knees; mean age, 36.6 years) were included with a minimum 2-year follow-up. The mean ± SD sizes of the patellar and trochlear lesions were 5.6 ± 2.7 cm2and 4.2 ± 2.8 cm2, respectively. Forty-two patients had osteotomy, as they had PF lateral maltracking, patellar instability, or tibiofemoral malalignment. Patients were evaluated with the modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, the 36-Item Short Form Health Survey, and a patient satisfaction survey. Radiographs were evaluated with the Iwano classification.Results:Overall, the survival rates were 83% and 79% at 5 and 10 years, respectively. Of the 49 (82%) knees with retained grafts, all functional scores significantly improved postoperatively with a very high satisfaction rate (88%) at a mean 8.8 ± 4.2 years after ACI (range, 2-16 years). At the most recent follow-up, 28 of 49 successful knees were radiographically assessed (mean, 4.9 years; range, 2-17 years), with no increase of the Iwano classification in 26 knees. Outcomes for 11 patients were considered failures at a mean 2.9 years. Forty-two knees (70%) required a mean 1.0 subsequent surgical procedure. The primary reasons for chondroplasty were hypertrophy of the ACI graft (17; periosteum in 14, collagen membrane in 3), delamination of the ACI graft (5; periosteum in 4, collagen membrane in 1), and new chondral lesions (3). The best survival rates were observed among patients who underwent ACI with concomitant tibial tubercle osteotomy (TTO) as the first procedure without previous failed TTO and/or marrow stimulation technique (91% at 5 and 10 years), while the worst survival rates were observed among patients who had previous marrow stimulation (43% at 5 and 10 years).Conclusion:Results demonstrated that ACI with concomitant osteotomy, when it is necessary for the treatment of bipolar/kissing lesions in the PF compartments, gives significant improvement in pain and function, with good survival rates at 5 and 10 years (83% and 79%, respectively). The high patient satisfaction rate is encouraging, and a high survival rate can be expected when ACI with a concomitant TTO is performed at the initial surgery for this difficult condition.

Purpose Customized Individually Made (CIM) Bicompartmental Knee Arthroplasty (BKA) implants and three-dimensional printed customized instruments are available to fit to each patient’s unique anatomy, medial or lateral with patellofemoral. This study aimed to evaluate the clinical outcomes after CIM-BKA. Methods Fifty-five patients [59 knees; average age, 51 years; standard deviation (SD), 6.8; range 37–65 years] who underwent CIM-BKA were evaluated over an average of 3.8-year follow-up (SD 1.6; range 1–6 years). Forty-one knees underwent BKA combined medial and patellofemoral replacement (BKA-MP) and 18 knees underwent BKA combined lateral with patellofemoral replacement (BKA-LP). Survival rates, the modified Cincinnati Knee Rating Scale, WOMAC, VAS, SF-36, a satisfaction survey, and radiographic evaluation were used to evaluate outcomes. Results Overall, survival rates were 98% and 92% at 2 and 5 years, respectively. Of 56 knees (95%) that did not fail, all patient-reported functional scores significantly improved post-operatively (P

International audience; The Message Passing Interface (MPI) plays a crucial part in the parallel computing ecosystem, a driving force behind many of the high-performance computing (HPC) successes. To maintain its relevance to the user community-and in particular to the growing HPC community at large-the MPI standard needs to identify and understand the MPI users' concerns and expectations, and adapt accordingly to continue to efficiently bridge the gap between users and hardware. This questionnaire survey was conducted using two online questionnaire frameworks and has gathered more than 850 answers from 42 countries since February 2019. Some of preceding surveys of MPI uses are questionnaire surveys like ours, while others are conducted either by analyzing MPI programs to reveal static behavior or by using profiling tools to analyze the dynamic runtime behavior of MPI jobs. Our survey is different from other questionnaire surveys in terms of its larger number of participants and wide geographic spread. As a result, it is possible to illustrate the current status of MPI users more accurately and with a wider geographical distribution. In this report, we will show some interesting findings, compare the results with preceding studies when possible, and provide some recommendations for MPI Forum based on the findings.

The optimal pain management strategy for postoperative pain after anterior cruciate ligament reconstruction (ACLR) remains unclear. This study compared femoral nerve block (FNB) and adductor canal block (ACB) for pain management of early postoperative pain, knee function, and recovery of activity of daily living (ADL) after ACLR using hamstring autografts. In this prospective, single-blind, randomised controlled trial, 64 patients aged 12–56 years who underwent anatomical double-bundle ACLR with a hamstring autograft between August 2019 and May 2020 were randomised to undergo preoperative FNB (n = 32) or ACB (n = 32). The peripheral nerve block was performed by a single experienced anaesthesiologist under ultrasound guidance. The primary outcomes were postoperative pain as evaluated using the visual analogue scale (VAS) at 3, 6, 12, 24, and 48 h postoperatively and the need for pain relief. The secondary outcome was knee function, including the recovery of range of motion, contraction of the vastus medialis, and stable walking with a double-crutch (ADL), as evaluated by blinded physical therapists. There were no significant differences in patient demographics between the two groups. The VAS scores, need for pain relief, knee function, and ADL did not significantly differ between the groups. FNB and ACB provided comparable outcomes related to early postoperative pain, knee function, and ADL after double-bundle ACLR using hamstring autografts. Further research is necessary to evaluate the mid- to long-term effect of each block on recovery of knee function and ADL. I.

Background: Little is known regarding the optimal treatment for displaced, purely chondral fragments in the knee. Purpose: To report the clinical and radiographic outcomes of chondral fragment fixation in adolescents through use of autologous bone pegs. Study Design: Case series; Level of evidence, 4. Methods: This retrospective, single-center study evaluated 6 patients (mean age, 12.9 years) who underwent fixation of chondral fragments (no visualized bone attached) using autologous bone pegs (mean postoperative follow-up, 5.2 years; range, 1.4-10.9 years). The causes were trauma (n = 5) and osteochondritis dissecans (n = 1). Lesions were located in the trochlear groove (lateral, n = 3; medial, n = 2) or posterior part of the lateral femoral condyle (n = 1). The mean lesion size was 3.8 cm2 (range, 0.8-9.0 cm2). Patients were evaluated via physical examination and magnetic resonance imaging (MRI) using magnetic resonance observation of cartilage repair tissue scores. Results: In total, 5 patients successfully returned to sports without restrictions at a mean of 7 months (range, 6-8 months) postoperatively. At the latest follow-up, these 5 patients had full range of motion and no joint effusion. The mean magnetic resonance observation of cartilage repair tissue score was 85 (range, 70-95) at a mean duration of 3 years (range, 1-5 years). One patient experienced failure at 1.3 years postoperatively after a traumatic injury and subsequently underwent removal of the fixed fragment and a drilling procedure. Conclusion: In most adolescents, fixation of chondral fragments with no visualized bony portion using autologous bone pegs provided a satisfactory success rate and good healing of cartilage tissue confirmed on MRI scans.

Objective The purpose of this study was first to externally validate the Oswestry Risk of Knee Arthroplasty index (ORKA-1) by applying it to an autologous chondrocyte implantation (ACI) patient cohort in the United States with a broader definition of failure than only arthroplasty, and second, to determine predictive factors for the risk of ACI failure as defined by the senior author. Design A total of 171 patients that underwent ACI were included to validate the ORKA-1 as all factors needed for calculation and outcomes were recorded. For Cox regression analysis, 154 patients were included as they completed preoperative Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner, Lysholm, International Knee Documentation Committee (IKDC), and 12-item Shor Form (SF-12) scores. Patient- and lesion-associated parameters were recorded for each patient. Results At final follow-up (maximum of 10 years post-ACI), a total of 27 patients (15.8%) were considered a failure by senior author’s definition. With ACI failure as endpoint, the mean survival was 7.96 years in risk group 1 and 5.4 years in risk group 5. Cox regression analysis identified preoperative KOOS Sport/Recreation as the only significant predictive factor for ACI failure ( P = 0.007). Conclusion The ORKA-1 is a helpful tool for surgeons to estimate an individual patient’s likelihood of ACI survival. Further studies with larger patient cohorts as well as a consensus definition of failure are needed to further refine predictors of ACI failure.

Treatment of N-substituted pyrroles with carbonyl compounds and nucleophiles under indium catalysis was found to be a promising method for preparing β-alkylpyrroles without contamination by α-alkylpyrroles. With this methodology, a variety of alkyl groups, which are primary, secondary, and tertiary as well as cyclic and functionalized types, can be introduced in place onto the pyrrole ring. The simplicity performable as a catalytic one-step process is one of the important features of this reaction. The substituent on the nitrogen atom of the product β-alkylpyrrole can be removed easily by literature procedures. Therefore, the indium-catalyzed β-alkylation plus the N-deprotection is a powerful system for all six variations, which are N-substituted and N-unsubstituted β-alkylpyrroles having primary, secondary, and tertiary alkyl groups. Our method is applicable to synthesizing, albeit in two steps, β-pyrrolyl-group-connected unsymmetrical tetraarylmethanes that have not been addressed thus far. Mechanistic studies showed the following three aspects: (1) dipyrrolylalkanes produced in situ from the pyrrole and carbonyl compound are key intermediates, (2) the selective β-alkylation is attributed to the selective elimination of an α-pyrrolyl group from the dipyrrolylalkane intermediates, and (3) the indium Lewis acid catalyst is indispensable for the progress of both stages.

BACKGROUND The influence of preoperative rehydration on the action of rocuronium has not yet been investigated. OBJECTIVE The objective is to evaluate the hypothesis that preoperative rehydration lowers arterial rocuronium plasma concentrations and changes its associated neuromuscular blocking effects during induction of anaesthesia. DESIGN Randomised, single-blinded study. SETTING A secondary hospital from October 2013 to July 2014. PATIENTS In total, 46 men undergoing elective surgery were eligible to participate and were randomly allocated into two groups. Exclusion criteria were severe hepatic, renal or cardiovascular disorder; neuromuscular disease; history of allergy to rocuronium; BMI more than 30 kg m; receiving medication known to influence neuromuscular function. INTERVENTION Participants received 1500 ml of oral rehydration solution (rehydration group) or none (control group) until 2 hours before anaesthesia. Arterial blood samples were obtained 60, 90 and 120 s and 30 min after rocuronium (0.6 mg kg) administration during total intravenous anaesthesia. Responses to 0.1-Hz twitch stimuli were measured at the adductor pollicis muscle using acceleromyography. MAIN OUTCOME MEASURES Arterial plasma rocuronium concentrations. RESULTS Arterial plasma rocuronium concentrations at 60, 90 and 120 s in the rehydration and control groups were 9.9 and 13.7, 6.8 and 9.5 and 6.2 and 8.1 μg ml, respectively (P = 0.02, 0.003 and 0.02, respectively); the onset times in the rehydration and control groups were 92.0 and 69.5 s (P = 0.01), and the times to twitch re-appearance were 25.3 and 30.4 min (P = 0.004), respectively. CONCLUSION Preoperative rehydration significantly reduces arterial plasma rocuronium concentrations in the first 2 minutes after administration, prolonging the onset time and shortening the duration of effect. A higher dose or earlier administration should be considered for patients who receive preoperative rehydration. TRIAL REGISTRATION Umin identifier: UMIN000011981.

We have developed a real-time graphical display that presents anesthetic pharmacology data (drug effect site concentrations (Ce) and probability of anesthetic effects including hypnosis, loss of response to tracheal intubation), improving a previous prototype. We hypothesized that the use of the display alters (1) clinical behavior of anesthesiologists (i.e., Ce of isoflurane and fentanyl at the end of anesthesia), (2) fentanyl dose during the first 30 min of recovery in the post anesthesia care unit (PACU), and that the response of clinicians to the display in terms of workload and utility is favorable. The display was evaluated in a two-group, non-randomized prospective observational study of 30 patients undergoing general anesthesia using isoflurane and fentanyl. The isoflurane-predicted Ce was lower in the display group (without-display: 0.64% ± 0.06%; with-display: 0.42 ± 0.04%; t

Background: Patient-reported outcome (PRO) measures are progressively utilized as evaluation tools in preoperative and postoperative assessments in orthopaedic practice. Identifying the potential utility of psychosocial factors to predict patient-reported pain and functional outcomes is of increasing interest to determine which patients will derive the greatest benefit from surgical treatment. Purpose/Hypothesis: The purpose of this study was to determine potential predictive associations between the preoperative 12-Item Short Form Health Survey Mental Component Summary (SF-12 MCS) score, patient characteristics or osteochondral allograft (OCA) morphology, and PROs in patients who underwent OCA transplantation. We hypothesized that poor preoperative mental health is associated with diminished PROs at final follow-up. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 67 patients with a mean follow-up of 2.7 ± 1.0 years (range, 2-6 years) with complete preoperative and at least 24-month postoperative SF-12 MCS, Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores were included in this study. Pearson correlation coefficients and linear regression models were used to distinguish associations between age, sex, smoking status, body mass index, workers’ compensation, previous surgery, concomitant surgery, number of grafts, defect location, total graft size, SF-12 MCS score, and postoperative PRO scores as well as their improvement from baseline (delta). Results: The SF-12 MCS showed significant correlation with the KOOS Activities of Daily Living subscale ( P = .015), KOOS Sport/Recreation subscale ( P = .024), and IKDC ( P = .039). In the multivariable linear regression models, the SF-12 MCS had no predictive association with any PRO measure. Patient sex contributed significantly to the final regression models of the KOOS Sport/Recreation ( P = .042), Tegner score ( P = .024), and Lysholm score ( P = .031). The SF-12 MCS showed no bivariate correlation with changes in any PRO score (delta) ( P > .05). Conclusion: Preoperative mental health status did not predict perceived functional outcomes as assessed by PRO measures at final follow-up. Female sex was negatively correlated with KOOS Sport/Recreation, Tegner, and Lysholm scores.

Objective Takedown of the anterior meniscus to facilitate exposure of the cartilage defects located on the tibial plateau and/or posterior femoral condyle with subsequent reattachment is being performed clinically; however, clinical evidence is lacking to support the safety of this technique. The aim of this study was therefore to investigate whether meniscal extrusion develops after patients undergo meniscus takedown and transosseous refixation during autologous chondrocyte implantation (ACI). Design We analyzed data from 124 patients with a mean follow-up of 6.8 ± 2.5 years. Sixty-two patients who underwent (ACI) with anterior meniscus takedown and refixation by the senior surgeon (TM), were compared with a matched control group of patients who underwent ACI without meniscus takedown. Meniscal extrusion was investigated by measuring the absolute value and the relative percentage of extrusion (RPE) on 1.5-T magnetic resonance images (MRI) at final follow-up. The number of menisci with radial displacement greater or lesser than 3 mm was determined. In cases where a preoperative MRI was available, both pre- and postoperative meniscal extrusion was evaluated ( n = 30) in those patients undergoing meniscal takedown. Results There was no significant difference in either absolute meniscus extrusion, RPE, or extrusion rate in patients with and without meniscus takedown. Among patients with meniscal takedown and both pre- and postoperative MRI scans, absolute meniscus extrusion, RPE, and extrusion rate showed no significant differences. Conclusion Meniscal takedown and subsequent transosseous refixation is a safe and effective technique for exposure of the tibial plateau and posterior femoral condyle.

We report enhancement of the transverse magneto-optic Kerr effect (TMOKE) in Au/Fe/Au trilayers for improving the refractive index (RI) sensitivity in surface plasmon resonance sensors by magnetic modulation. The thicknesses of the upper Au layer, the Fe layer and the lower Au layer with required thickness resolution were theoretically optimized to maximize the TMOKE intensity with perfect momentum matching, and 3% TMOKE intensity was obtained in a trilayer. Furthermore, a wedge-shaped Au thin film was fabricated on a glass substrate, and the incident angle showing minimum reflectivity was modulated, corresponding to a difference in momentum matching. Resolution of the metal layer thickness (0.26 nm) was demonstrated in a single sensor chip for maximizing the TMOKE intensity. Enhanced RI resolution is expected in sensor chips formed of a Au/Fe/wedge Au trilayer, which will contribute to improvements in the limit of detection when measuring the analytes by analyzing the resulting signals.

The use of vegetable proteins as food ingredient is becoming increasingly important due to their high versatility and environmental acceptability. This work describes a chemical characterization and techno-functional properties (emulsifying and foaming properties) of 3 protein fractions obtained from a protein-rich novel lupin variety, AluProt-CGNA(®) . This nongenetically modified variety have a great protein content in dehulled seeds (60.6 g protein/100 g, dry matter), which is higher than soybean and other lupin varieties. A simple procedure was utilized to obtain 3 different fractions by using alkali solubilization and isoelectric precipitation. Fractions 1 and 3 were mainly composed of protein and polysaccharides (NNE), whereas fraction 2 was mainly composed by protein (97%, w/w). Fraction 3 presented interesting and potential foaming properties in comparison to the other fractions evaluated in the study. Besides, its solubility, foaming and emulsifying capacity were practically not affected by pH variations. The 3 fractions also presented good emulsion stability, reaching values above a 95%. SDS-PAGE showed that fractions 1 and 2 contained mainly conglutin α, β, and δ, but in different ratios, whereas fraction 3 contained mainly conglutin γ and albumins. The results of this work will provide better understanding for the utilization of each protein fractions as potential ingredients in food industry.

Objectives: Static anterior tibial subluxation after an anterior cruciate ligament (ACL) injury highlights the abnormal relationship between the tibia and femur in patients with ACL insufficiency. One of the aims of ACL reconstruction is to restore the normal tibiofemoral relationship. However, several studies indicated that an abnormal tibiofemoral relationship remained after single-bundle (SB) ACL reconstruction. The purpose of this study was to determine the serial changes of static relationship between tibia and femur in patient who had double-bundle ACL reconstruction with acute and chronic injuries. Methods: Thirty five patients who underwent double-bundle ACL reconstruction between January 1 to July 31, 2017 were included in this prospective study and divided two groups: the acute ACL injury group and the chronic ACL injury group (more than 6 month after injury). All participants underwent preoperative and postoperative magnetic resonance imaging (MRI) at 3 weeks, 3, 6 and 12 months. Anterior tibial subluxation (ATS) of the medial and lateral compartments relative to the femoral condyles were measured on MRI. Results: There were no significant differences in the age and KT side to side difference between both groups (Table 1). The ATS measurements are shown in table 2. In lateral compartment, the ATS in the acute ACL injury group was 5.3mm before surgery, while it was -0.31mm, 3.4mm, 3.5mm and 4.9mm at 3 weeks, 3, 6, 12months after surgery, respectively. The ATS in the chronic ACL injury group was 6.7mm before surgery, while it was 0.47mm, 3.9mm, 4.6mm and 5.9mm at 3 weeks, 3, 6, 12months after surgery, respectively. No significant difference was found between 2 groups. In medial compartment, the ATS in the acute ACL injury group was 1.8mm before surgery, while it was -1.6mm, 0.28mm, 0.93mm and 2.1mm at 3 weeks, 3, 6, 12months after surgery, respectively. The ATS in the chronic ACL injury group was 2.5mm before surgery, while it was -1.4mm, 1.6mm, 1.7mm and 3.0mm at 3 weeks, 3, 6, 12months after surgery, respectively. No significant difference was found between 2 groups. Conclusion: In both of lateral and medial compartment, the ATS was not significant different between acute and chronic ACL injuries before surgery. In lateral compartment, at 3 weeks, 3months and 6months after surgery, ATS was significantly less than before surgery in both groups. At 12 months, ATS was not significant different from before surgery in both groups. In medial compartment, at 3 weeks, ATS were significantly less than before surgery in both groups. After 3 months, ATS was not significant different from before surgery in both groups. The ATS was not significant different between acute and chronic ACL injuries in the same period after surgery. [Figure: see text][Figure: see text][Figure: see text][Figure: see text]

Objective We sought to determine the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) associated with the Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Lysholm, and Short Form–12 (SF-12) after autologous chondrocyte implantation (ACI). Design Ninety-two patients with satisfaction surveys at a minimum of 2 years postoperatively and at least 1 repeated patient-reported outcome measure (PROM) were analysed. The MCID was determined using 4 anchor-based methods: average change, mean change, minimally detectable change, and the optimal cutoff point for receiver operating characteristic (ROC) curves. If an anchor-based method was not applicable, standard deviation–based and effect size–based estimates were used. SCB was determined using ROC curve analysis. Results The 4 anchor-based methods provided a range of MCID values for each PROM (11-18.8 for the KOOS pain, 9.2-17.3 for the KOOS activities of daily living, 12.5-18.6 for the KOOS sport/recreation, 12.8-19.6 for the KOOS quality of life, 10.8-16.4 for the IKDC, and 6.2-8.2 for the SF-12 physical component summary). Using the 2 distribution-based methods, the following MCID value ranges were obtained: KOOS symptom, 3.6 to 8.4; the Lysholm, 4.2 to 10.5; and the SF-12 mental component summary, 1.9 to 4.6. SCB was 30 for the KOOS sport/recreation and 34.4 for the IKDC, which most accurately predict substantial improvement. No significant association was noted between SCB achievement and the baseline PROMs. Conclusion The MCID and SCB determined in our study will allow interpretation of the effects of treatment in clinical practice and trials. Given the varied MCID values in this study, standardisation of the most appropriate calculation methods is warranted.

ObjectiveThe purpose of this study was to assess potential correlations between the mental component summary of the Short Form–12 (SF-12 MCS), patient characteristics or lesion morphology, and preoperative self-assessed pain and function scores in patients undergoing autologous chondrocyte implantation (ACI).DesignA total of 290 patients underwent ACI for symptomatic cartilage lesions in the knee. One hundred and seventy-eight patients were included in this study as they completed preoperative SF-12, Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores. Age, sex, smoker status, body mass index, Worker’s Compensation, previous surgeries, concomitant surgeries, number of defects, lesion location in the patella, and total defect size were recorded for each patient. Pearson’s correlation and multivariate regression models were used to distinguish associations between these factors and preoperative knee scores.ResultsThe SF-12 MCS showed the strongest bivariate correlation with all KOOS subgroups ( P < 0.001) (except KOOS Symptom; P = 0.557), Tegner ( P = 0.005), Lysholm ( P < 0.001), and IKDC scores ( P < 0.001). In the multivariate regression models, the SF-12 MCS showed the strongest association with all KOOS subgroups ( P < 0.001) (except KOOS Symptom; P = 0.91), Lysholm ( P = 0.001), Tegner ( P = 0.017), and IKDC ( P < 0.001).ConclusionIn patients with symptomatic cartilage defects of the knee, preoperative patient mental health has a strong association with self-assessed pain and functional knee scores. Further studies are needed to determine if preoperative mental health management can improve preoperative symptoms and postoperative outcomes.

Purpose To assess and compare meniscal extrusion rates after lateral “bridge-in-slot” meniscal allograft transplantation (MAT) with arthroscopic versus open insertion. Methods In this review of prospectively collected data, we analyzed data from patients who underwent arthroscopic or open lateral MAT. Patients who underwent concomitant distal femoral osteotomy, for whom 1-year postoperative magnetic resonance imaging was unavailable, or who underwent open lateral MAT without the use of transosseous sutures were excluded. Meniscal extrusion in the included patients was assessed by 2 independent examiners by measuring the absolute value and the relative percentage of extrusion on 1.5-T magnetic resonance images at 1-year follow-up. The number of MATs with radial displacement larger or smaller than 3 mm was determined. Results A total of 20 patients met the inclusion criteria, of whom 10 underwent arthroscopic and 10 underwent open lateral MAT. No statistically significant differences were found in baseline demographic data. Absolute meniscal extrusion was similar between the groups (P = .091). A significantly larger relative percentage of extrusion (arthroscopic MAT, 31 ± 27 mm; open MAT, 10 ± 29 mm; 95% confidence interval, –0.4 to –0.02 mm; P = .03) and a significantly higher extrusion rate were found in patients treated with arthroscopic MAT than in those treated with open MAT (>3 mm in 5 patients [50%] with arthroscopic MAT and 0 patients with open MAT, P = .01). Conclusions This study identified similar absolute extrusion and significantly lower postoperative lateral meniscal extrusion rates after open MAT compared with arthroscopic MAT. Transosseous fixation of the meniscal body appears protective against meniscal extrusion after MAT. Level of Evidence Level III, case-control study.

Background:Treating bipolar chondral lesions in the tibiofemoral (TF) compartment with cartilage repair procedures is challenging, and a suitable treatment remains unclear.Purpose:To evaluate clinical outcomes after autologous chondrocyte implantation (ACI) for the treatment of bipolar chondral lesions in the TF compartment.Study Design:Case series; Level of evidence, 4.Methods:We evaluated 57 patients who underwent ACI for the treatment of symptomatic bipolar chondral lesions in the TF compartment by a single surgeon between October 1995 and June 2014. One patient did not return for follow-up. Thus, 56 patients (58 knees) were included with a minimum of 2 years’ follow-up. A mean of 3.1 lesions per knee were treated, representing a mean total surface area of 16.1 cm2(range, 3.2-44.5 cm2) per knee. Bipolar lesions were present in the medial compartment (32 knees) and in the lateral compartment (26 knees). Patients were evaluated with the modified Cincinnati Knee Rating Scale, visual analog scale for pain, Western Ontario and McMaster Universities Osteoarthritis Index, and Short Form–36. Patients also answered questions regarding self-rated knee function and satisfaction with the procedure. Standard radiographs were evaluated with the Kellgren-Lawrence grading system.Results:The survival rate was 80% at 5 years and 76% at 10 years. A significantly better survival rate was found in patients with the use of a collagen membrane than periosteum (97% vs 61% at 5 years, respectively; P = .0014). Of 46 knees with retained grafts, all functional scores significantly improved postoperatively, with a very high satisfaction rate (91%) at a mean of 8.3 ± 5.1 years (range, 2-20 years) after ACI. At last follow-up, 24 of 46 successful knees were radiographically assessed (mean, 5.5 ± 4.0 years [range, 2.0-18.7 years]) and showed no significant osteoarthritis progression ( P = .3173). Outcomes for 12 patients were considered as failures at a mean of 4.1 years. Of these, 9 patients were converted to partial or total knee arthroplasty at a mean of 4.4 years. Two patients underwent revision ACI at 5 and 17 months. The other 1 patient did not require revision surgery.Conclusion:Our study showed that ACI for the treatment of bipolar chondral lesions in the TF compartment provided successful clinical outcomes in patients with retained grafts and possibly prevented or delayed osteoarthritis progression at midterm to long-term follow-up. A collagen membrane is more encouraging than periosteum for bipolar lesions in the TF compartment. While addressing the predisposing factors affecting cartilage repair, ACI could be an adequate salvage procedure for bipolar chondral lesions in the TF compartment for the relatively young arthritic patient who wishes to avoid arthroplasty.

Objective The effects of hydrostatic pressure (HP) on the matrix synthesis by human articular chondrocytes have been reported elsewhere. In order to optimize the production of extracellular matrix, we aimed to clarify the effects of repetitive HP on metabolic function by human articular chondrocytes. Design The human articular chondrocytes were expanded and embedded within a collagen gel/sponge scaffold. We incubated these constructs with and without HP followed by atmospheric pressure (AP) and repeated the second HP followed by AP over 14 days. Genomic, biochemical, and histological evaluation were performed to compare the effects of each regimen on the constructs. Results The gene expressions of collagen type II and aggrecan core protein were significantly upregulated with repetitive HP regimens compared with a single HP or AP by 14 days ( P < 0.01 or 0.05). Matrix metalloptoteinase-13 (MMP-13) in AP was upregulated significantly compared to other HP regimens at day 14 ( P < 0.01). No significant difference was observed in tissue inhibitor of metalloproteinases-II. Immunohistology demonstrated that application of HP (both repetitive and single) promoted the accumulation of specific extracellular matrix and reduced a MMP-13. A single regimen of HP followed by AP significantly increased the amount of sulfated glycosaminoglycan than that of the AP, whereas repetitive HP remained similar level of that of the AP. Conclusions Repetitive HP had a greater effect on anabolic activity by chondrocytes than a single HP regimen, which will be advantageous for producing a matrix-rich cell construct.

Autologous chondrocyte implantation is a promising therapy for the treatment of the articular cartilage defects. Recently, we have developed a three-dimensional chondrocyte construct manufactured with a collagen gel/sponge scaffold and cyclic hydrostatic pressure. However, the roles of various mechanical stresses, specifically hydrostatic pressure and deviatoric stress, as well as poststress loading, were unclear on metabolic function in chondrocytes. We hypothesized that hydrostatic pressure and deviatoric stresses each alter individual metabolic characteristics of chondrocytes. We embedded human articular chondrocytes within an agarose hydrogel and applied hydrostatic pressure and/or deviatoric stress individually or simultaneously for 4 days. Subsequently, we kept the cell constructs without stress for an additional 3 days. With hydrostatic pressure and/or deviatoric stress, more cells proliferated significantly than no stress (p < .05) and more cells proliferated near the inner side of the construct than the outer (p < .05). Cartilage specific aggrecan core protein and collagen type II were upregulated significantly after off-loading hydrostatic pressure alone at Day 7 (p < .05). On the other hand, these molecules were upregulated significantly immediately after deviatoric stress alone and combined with hydrostatic pressure at Day 4 (p < .05). Tissue inhibitor of metalloproteinase-2 was upregulated significantly after off-loading hydrostatic pressure alone and combined deviatoric stress at Day 7 (p < .05). Metalloproteinnase-13 was upregulated significantly with deviatoric stress at Day 4 (p < .05) and combined with hydrostatic pressure at Day 4. These results suggest that metabolic functions are regulated by the combination of hydrostatic pressure and deviatoric stress and by the timing of stress loading.

JM-1232(−) (JM) is a novel isoindoline derivative with sedative and hypnotic activities that are mediated by binding to the benzodiazepine site of the Gamma-aminobutyric acid type A (GABAA) receptor. Although the neuroprotective effects of other GABAA receptor agonists are well known, there is no published report regarding JM. Thus, we examined the effects of JM on neurons exposed to oxygen-glucose deprivation (OGD) using rat hippocampal slice cultures. Hippocampal slices were assigned to either control or JM-administered groups. To assess the neuroprotective effects of JM from necrotic changes, we measured the fluorescence of propidium iodide and compared the cell mortality 24 h following OGD between the control and JM-administered groups. We also verified that the effects of JM were mediated by GABAA receptors by adding flumazenil, a benzodiazepine receptor antagonist, in the same experimental settings. JM, at concentrations of 250 and 500 µM, significantly reduced cell mortality in pyramidal neurons after OGD; however, flumazenil did not inhibit this effect. To analyze more immediate effects of JM, we next measured the fluorescence of Oregon Green 488 BAPTA-1 during the OGD and re-oxygenation periods, and evaluated changes in intracellular Ca2+ in single CA1 pyramidal neurons. JM reduced the elevation of intracellular Ca2+ concentration during OGD, and this effect was antagonized by flumazenil. These findings indicate that JM suppressed the elevation of intracellular Ca2+ concentration during OGD through GABAA receptors, but its neuroprotective effects from necrotic changes also involve other unknown mechanisms.

The purpose of this study was to evaluate the signal/noise quotient (SNQ) for graft maturation and the serial changes observed in the magnetic resonance imaging (MRI) findings after double-bundle (DB) anterior cruciate ligament (ACL) reconstruction using a hamstring tendon autograft at a minimum of 5 years after surgery. Forty-five patients who underwent DB ACL reconstruction between 2007 and 2010 were included in this prospective study. All participants underwent postoperative MRI at 3 weeks and 3, 6, 9 and 12, 18, 24, 36, 48 and 50 months. The signal intensity (SI) characteristics of the reconstructed graft were evaluated on oblique axial proton density-weighted MR imaging (PDWI) perpendicular to the grafts. The signal/noise quotient (SNQ) was calculated to quantitatively determine the normalized SI. The SNQ of the AMB and PLB was evaluated separately. The mean SNQ of the AM bundle (AMB) continued to increase until 6 months after surgery (5.2 ± 1.2), and then gradually decreased and became well stabilized by 18 months (3.3 ± 0.5), after which it remained unchanged. On the other hand, the mean SNQ of the PL bundle (PLB) continued to increase until 9 months after surgery (6.2 ± 1.1), and then decreased incrementally and became well stabilized by 24 months (4.1 ± 0.5). The SI of PLB was significantly higher than that of AMB between 3 and 24 months (p = 0.04, 0.03, 0.01, 0.04, 0.02 and 0.03, respectively). These results indicate that at least 18 months is needed after ACL reconstruction to sufficiently restore the SI of the AMB, while at least 24 months are needed to for the PLB. The SI of the PLB was significantly higher than that of the AMB at 3–24 months after surgery, indicating that the PLB showed inferior graft maturity to the AMB until 24 months after surgery. For clinical relevance, the correct understanding of serial changes in graft maturation may potentially be used in decision-making regarding a return to sports. Prospective case series, Level IV.