Search

Protein aggregation is the underlying cause of many diseases, and also limits the usefulness of many natural and engineered proteins in biotechnology. Better mechanistic understanding and characterization of aggregation-prone states is needed to guide protein engineering, formulation, and drug-targeting strategies that prevent aggregation. While several final aggregated states—notably amyloids—have been characterized structurally, very little is known about the native structural conformers that initiate aggregation. We used a novel combination of small-angle x-ray scattering (SAXS), atomistic molecular dynamic simulations, single-molecule Förster resonance energy transfer, and aggregation-prone region predictions, to characterize structural changes in a native humanized Fab A33 antibody fragment, that correlated with the experimental aggregation kinetics. SAXS revealed increases in the native state radius of gyration, Rg, of 2.2% to 4.1%, at pH 5.5 and below, concomitant with accelerated aggregation. In a cutting-edge approach, we fitted the SAXS data to full MD simulations from the same conditions and located the conformational changes in the native state to the constant domain of the light chain (CL). This CL displacement was independently confirmed using single-molecule Förster resonance energy transfer measurements with two dual-labeled Fabs. These conformational changes were also found to increase the solvent exposure of a predicted APR, suggesting a likely mechanism through which they promote aggregation. Our findings provide a means by which aggregation-prone conformational states can be readily determined experimentally, and thus potentially used to guide protein engineering, or ligand binding strategies, with the aim of stabilizing the protein against aggregation.

This study is an investigation into the possibility of using rice husk ash blended with cement (CRHA) in the modification of the basic engineering properties of a marginal lateritic soil with the aim of qualifying the soil for use in the construction of roads. In the study, the properties of the natural soil sample such as bearing strength (measured in California Bearing Ratio: CBR), compaction behaviour as well as other consistency parameters were evaluated. The same properties were also evaluated for the soil samples modified with C-RHA. The findings of the study show that an increase in values of the C-RHA results a decrease in plasticity. An improvement in the CBR was observed with increasing value of the RHA at specified cement contents with peak values at 5% cement and 10% RHA. This indicates the potential of using 7.5-10% RHA admixed with 5% cement contents for laterite soil stabilization for use as a sub-grade soil for road construction.Keywords: Cement, Compaction behaviour, Lateritic soil, Rice husk ash, Soil stabilization, Road construction

Revision total knee arthroplasty (RTKA) represents an effective treatment for failed TKA, but with less favorable outcomes. Considering the technical complexity and economic burden of RTKA procedures, it is mandatory to investigate current mechanisms and predictors for RTKA failure. The objective of this study is to evaluate the survivorship and determine the predominant causes of failure of RTKA. A total of 146 patients undergoing RTKA between 2003 and 2013 were identified from the institutional database. Revision was defined as surgery in which the whole prostheses (inlay and both femoral and tibial components) required exchange. Median follow-up was 6.3 ± 2.7 years (range: 2.2-10). Patient demographics, year of primary implantation, reasons for revision surgery, implant type, pain, knee mobility, systemic or local postoperative complications, and treatment of the complications were recorded and evaluated. Infection was a major cause of failure followed by aseptic loosening, instability, pain, malalignment, and inlay wear. Following RTKA, Knee Society Score (KSS) (knee score and functional score) demonstrated a significant improvement (p < 0.05). No significant difference in flexion, extension deficit, and KSS was detected between aseptic and septic primary TKAs preoperatively and following first RTKA. Reinfection rate of the septic primary TKAs was 5%. Infection was the major cause of a second revision, reaching as high as 50% in all cases. The results of this study support that septic failure of a primary TKA is likely to occur within the first 2 years following implantation. Septic failure of primary TKA does not influence survival of the revision prosthesis. © 2019 Georg Thieme Verlag. All rights reserved.

Background: Recently, a new technique, dynamic intraligamentary stabilization (DIS) was introduced for the acute repair of ACL ruptures. The purpose of this study was to report the functional recovery for patients undergoing acute anterior cruciate ligament (ACL) repair alongside DIS. Methods: Forty five patients sustaining acute ACL rupture and treated with DIS repair were retrospectively evaluated. Limb symmetry index of the hop test as well as knee function by means of range of motion, knee swelling, pain and maximum strength were evaluated. Following completion of the rehabilitation program, the difference in anterior-posterior translation (δ-AP Translation), IKDC, Tegner score (TAS) was additionally analyzed. Results: Forty five (13 females, 32 males) patients were included in the study. Mean age was 26 years (range 18 to 54 years). Median time to successfully complete hop test was 22.0 weeks (range 11 to 32 weeks) postoperatively. Median limb symmetry index 91.6% ± 8.3%. Median delta anterior-posterior translation compared to the healthy side was plus 0.0 mm ± 1.6 mm. Median IKDC was 89.5 ± 6.5. Mean Tegner score (TAS) at 12 months of follow-up was seven (range four to nine). Three patients suffered a rerupture during the first 12 postoperative months. Conclusions: DIS technique with proper rehabilitation following acute ACL rupture provides successful functional recovery and low rerupture rate at one-year follow-up. © 2016 Elsevier B.V.

Background: Arthroscopy is considered as "the gold standard" for the diagnosis of traumatic intraarticular knee lesions. However, recent developments in magnetic resonance imaging (MRI) now offer good opportunities for the indirect assessment of the integrity and structural changes of the knee articular cartilage. The study was to investigate whether cartilage-specific sequences on a 3-Tesla MRI provide accurate assessment for the detection of cartilage defects. Methods: A 3-Tesla (3-T) MRI combined with three-dimensional double-echo steady-state (3D-DESS) cartilage specific sequences was performed on 210 patients with knee pain prior to knee arthroscopy. Sensitivity, specificity, and positive and negative predictive values of magnetic resonance imaging were calculated and correlated to the arthroscopic findings of cartilaginous lesions. Lesions were classified using the modified Outerbridge classification. Results: For the 210 patients (1260 cartilage surfaces: patella, trochlea, medial femoral condyle, medial tibia, lateral femoral condyle, lateral tibia) evaluated, the sensitivities, specificities, positive predictive values, and negative predictive values of 3-T MRI were 83.3, 99.8, 84.4, and 99.8 %, respectively, for the detection of grade IV lesions; 74.1, 99.6, 85.2, and 99.3 %, respectively, for grade III lesions; 67.9, 99.2, 76.6, and 98.2 %, respectively, for grade II lesions; and 8.8, 99.5, 80, and 92 %, respectively, for grade I lesions. Conclusions: For grade III and IV lesions, 3-T MRI combined with 3D-DESS cartilage-specific sequences represents an accurate diagnostic tool. For grade II lesions, the technique demonstrates moderate sensitivity, while for grade I lesions, the sensitivity is limited to provide reliable diagnosis compared to knee arthroscopy. © 2015 Kohl et al.

Objective: Arthroscopy is the gold standard for the diagnosis of knee cartilage lesions. However, it is invasive and expensive, and displays all the potential complications of an open surgical procedure. Ultra-high-field MRI now offers good opportunities for the indirect assessment of the integrity and structural changes of joint cartilage of the knee. The goal of the present study is to determine the site of early cartilaginous lesions in adults with non-traumatic knee pain. Methods: 3-T MRI examinations of 200 asymptomatic knees with standard and three-dimensional doubleecho steady-state (3D-DESS) cartilage-specific sequences were prospectively studied for early degenerative lesions of the tibiofemoral joint. Lesions were classified and mapped using the modified Outerbridge and modified International Cartilage Repair Society classifications. Results: A total of 1437 lesions were detected: 56.1% grade I, 33.5% grade II, 7.2% grade III and 3.3% grade IV. Cartographically, grade I lesions were most common in the anteromedial tibial areas; grade II lesions in the anteromedial L5 femoral areas; and grade III in the centromedial M2 femoral areas. Conclusion: 3-T MRI with standard and 3D-DESS cartilagespecific sequences demonstrated that areas predisposed to early osteoarthritis are the central, lateral and ventromedial tibial plateau, as well as the central and medial femoral condyle. Advances in knowledge: In contrast with previous studies reporting early cartilaginous lesions in the medial tibial compartment and/or in the medial femoral condyle, this study demonstrates that, regardless of grade, lesions preferentially occur at the L5 and M4 tibial and L5 and L2 femoral areas of the knee joint. © 2015 The Authors.

Background Traumatic knee dislocation represents a rare but devastating injury. Several controversies persist regarding type of treatment, surgical timing, graft selection, repair versus reconstruction of the medial and lateral structures, surgical techniques and postoperative rehabilitation. A new technique for primary ACL stabilization, dynamic intaligamentary stabilization (DIS) was developed at the authors' institution. The purpose of this study was to analyze the clinical and radiological outcomes of surgically treated traumatic knee dislocations by means of the DIS technique for the ACL, primary suturing for PCL, MCL and LCL. Methods Between 2009 and 2012, 35 patients treated surgically for traumatic knee dislocation with primary anterior cruciate ligament (ACL) reconstruction with DIS, suturing of the posterior cruciate ligament (PCL) and primary complete repair of collaterals, were evaluated clinically (IKDC score, SF12 health survey, Lysholm score, Tegner score) and radiologically with a mean follow up of 2.2 years (range 1.00-3.50 years) years. Instrumented anterior-posterior translation was measured (KT-2000). Results Anterior/posterior translation (KT-2000) for the healthy and injured limb was 4.8 mm (range 3-8 mm) and 7.3 mm (range 5-10) (89 N) respectively. Valgus and varus stress testing in 30° flexion was normal in 26 (75%) and 29 (83%) patients, respectively. The IKDC score was B in 29 (83%) and C in 6 (17%) patients, while the mean Tegner score was 6 (range 4-8). The mean Lysholm score was 90.83 (range 81-95) and mean SF-12 physical and mental scores were 54.1 (range 45-60) and 51.0 (range 39-62) respectively. In 2 patients, a secondary operation was performed. Conclusions Early, one stage reconstruction with DIS can achieve good functional results and patient satisfaction with overall restoration of sports and working capacity without graft requirements. © 2014 Elsevier Ltd. All rights reserved.

Increased urbanisation throughout South Asia has increased the number and output of the brick kilns that typically surround major cities, but the environmental and health impacts of their atmospheric emissions are poorly understood in Pakistan. We report the negative effects of hydrogen fluoride (HF) emissions from brick kilns near Peshawar, Pakistan on mung bean (Vigna radiata cv. MN 92) and maize (Zea mays cv. Azam). HF air concentrations, and fluoride concentrations of mung bean and maize grains, were greater close to brick kilns than at more distant sites. The 100-grain weight of mung bean and maize close to brick kilns was significantly lower, by about 30% and 45% respectively, than at control sites. These findings, added to evidence of major impacts on local fruit orchards in this area, suggest that fluoride emissions from brick kilns may have a significant impact on pen-urban agriculture in South Asia.

Background: Anterior cruciate ligament (ACL) rupture is a common lesion. Current treatment emphasizes arthroscopic ACL reconstruction via a graft, although this approach is associated with potential drawbacks. A new method of dynamic intraligamentary stabilization (DIS) was subjected to biomechanical analysis to determine whether it provides the necessary knee stability for optimal ACL healing. Methods: Six human knees from cadavers were harvested. The patellar tendon, joint capsule and all muscular attachments to the tibia and femur were removed, leaving the collateral and the cruciate ligaments intact. The knees were stabilized and the ACL kinematics analyzed. Anterior-posterior (AP) stability measurements evaluated the knees in the following conditions: (i) intact ACL, (ii) ACL rupture, (iii) ACL rupture with primary stabilization, (iv) primary stabilization after 50 motion cycles, (v) ACL rupture with DIS, and (vi) DIS after 50 motion cycles. Results: After primary suture stabilization, average AP laxity was 3.2. mm, which increased to an average of 11.26. mm after 50 movement cycles. With primary ACL stabilization using DIS, however, average laxity values were consistently lower than those of the intact ligament, increasing from an initial AP laxity of 3.00. mm to just 3.2. mm after 50 movement cycles. Conclusions: Dynamic intraligamentary stabilization established and maintained close contact between the two ends of the ruptured ACL, thus ensuring optimal conditions for potential healing after primary reconstruction. The present ex vivo findings show that the DIS technique is able to restore AP stability of the knee. © 2013 Elsevier B.V.

A 75-year-old male patient was referred to our orthopaedic department due to progressive weakening of the left leg, noticed while going up and down stairs, and swelling of the thigh. An increase in swelling was noted in association with spicy food. Clinical examination showed a palm-sized non-pulsatile soft mass in the popliteal region and swelling in the posterior-lateral thigh. MRI revealed a space-occupying 40×15×10 cm mass extending into the upper thigh without infiltrating character. Angiography was negative. Open surgical biopsy was performed to rule out a soft tissue tumour, during which, connection to the popliteal artery was identified. The patient underwent excision of the aneurismal sac and a prosthetic graft was interplaced. On follow-up, the patient noticed a rapid increase in muscle strength; stairs were no longer a problem.

Einleitung: Die morbide Adipositas (Adipositas per magna) ist ein weltweites Problem, das eine zunehmende und alarmierende Inzidenzrate hat. Die chirurgische Therapie hat bis jetzt ein signifikant-effektiveres und länger anhaltendes Ergebniss als konservative Maßnahmen gezeigt. Mit dieser[for full text, please go to the a.m. URL], 126. Kongress der Deutschen Gesellschaft für Chirurgie

The effect of operational-amplifier nonlinearity on the performance of active-R, active-C, and “partial” active-R filters is investigated. Theoritical and experimental results show that the amplifier slew-rate limitation results in a characteristic which slants from the ideal flat response of the filter transfer functions.