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Abstract The natural anthraquinone rhein has been identified as a novel herbicide with a potentially new mode of action using a generative AI system for functional molecules discovery. Its herbicidal activity was light-dependent and resulted in rapid burndown symptoms on leaves of treated plants. Rhein interferes with photosynthesis by acting as an electron diverter at the level of photosystem I (PSI). The redox potential of rhein suggests that it accepts electrons between P700 and NADP+ of PSI. This is consistent with the redox potential of rhein that enables it to accept electrons from flavoproteins. Ferredoxin-NAPD+ reductase is a flavoprotein with a redox potential near that of rhein. Thus, it is currently hypothesized that rhein acts as an electron acceptor at or near the PSI Ferredoxin-NAPD+ reductase to form a radical and generate reactive oxygen species that drive the light-dependent herbicidal effect which is observed in treated plants from greenhouse trials.

Summary: The Fracture Improvement with Teriparatide (Fix-IT) study randomized 13 women with an atypical femur fracture to immediate vs delayed teriparatide therapy; all were followed for 12 months. Results suggested a trend for superior healing and lesser bone mineral density declines in the immediate vs delayed group with no differences in adverse events.Purpose: Little clinical data are available on the use of teriparatide for the treatment of bisphosphonate-associated atypical femur fractures (AFF). The goal of the Fix-IT study was to determine if immediate therapy with teriparatide was superior for fracture healing after an AFF compared to a 6-month delay in teriparatide therapy.Methods: This randomized pilot clinical trial included 13 women with an AFF who were randomized to immediate teriparatide vs a delay of 6 months. All were followed for 12 months on teriparatide. The primary outcomes included individual and composite measures of radiologic bone healing (scored 1 point [no healing] to 4 points [complete healing]) at 6 and 12 months. Secondary outcomes included bone mineral density of the unfractured contralateral hip, spine, 1/3 distal radius, and adverse events.Results: We found there was a trend for superior healing with the composite score (12.6 vs 11.2 at 6 months and 15.4 vs 13.2 at 12 months), and lesser bone mineral density declines at the 1/3 distal radius (12-month change − 1.9 vs − 6.1%) in the immediate vs the delayed group. There were no differences in adverse events. There was one implant failure in the delayed group.Conclusions: There is a preliminary signal for greater improvements with immediate teriparatide therapy vs delayed therapy. However, because an AFF is a rare event, and only a small number of patients were included, the results must be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: This study was undertaken to provide a basis for decision-making when a well-fixed cemented cup is encountered at the time of a revision of a femoral component of a total hip replacement. It may be beneficial to retain the cup in some instances and thus reduce morbidity, complications, blood loss, operative time, and cost.Methods: All patients who had a revision of the femoral component and retention of an all-polyethylene acetabular component from 1971 to 1996 were identified. Three hundred and seventy-four patients with a total of 395 cemented total hip replacements fit the inclusion criteria. The gender, date of and age at the index surgery, type of acetabular implant, and time of and reason for the revision of the femoral component were reviewed. The time to subsequent cup revision or latest surveillance was noted. The average age (and standard deviation) was 66.5 +/- 11.8 years at the time of the femoral revision, which was performed at an average of 8.0 +/- 4.4 years after the primary arthroplasty. For the purposes of this study, the end point for survival of the acetabular component was cup revision for any reason.Results: At the time of the latest follow-up, at an average of nine years after the femoral revision and 17.3 years after the primary arthroplasty, 342 (86.6%) of the 395 cups remained in situ. Fifty-three cups (13.4%) in fifty-two patients had been revised, at an average of 10.0 +/- 5.7 years after the femoral revision and 16.7 +/- 5.3 years after the primary arthroplasty. The rate of survival of the retained acetabular components was 96.9% at five years, 89.3% at ten years, and 78.7% at fifteen years after the femoral revision and was 95.1% at fifteen years and 87.1% at twenty years after the primary arthroplasty. Increased age (p < 0.0001) and a shorter time-interval (less than 7.5 years) between the primary arthroplasty and the femoral revision (p = 0.05) were significantly associated with an increased likelihood of survival free of cup revision. Femoral head size, acetabular component design, gender, and primary diagnosis did not affect prosthetic survival in this sample of patients.Conclusions: The likelihood of survival of the unrevised cup was associated with patient age and duration of implantation, with the age of the patient being the more dominant factor predicting failure of the acetabular component. [ABSTRACT FROM AUTHOR]

The ability of unicompartmental knee arthroplasty (UKA) to restore native knee kinematics during activities of daily living remains unclear. The objectives of this prospective study were to identify changes in knee kinematics after medial UKA (mUKA) and to determine if mUKA restores native knee kinematics during activities of daily living. We hypothesized that kinematics are different between the mUKA knee and contralateral knee before surgery, that mUKA restores native knee kinematics, and that mUKA does not affect lateral compartment dynamic joint space. Nine participants performed walking, chair rise, stair ascent and stair descent within a biplane radiography system before and after mUKA. Bilateral knee kinematics were determined for each activity using a validated tracking process that matched subject-specific bones and implants to the biplane radiographs. Compared to contralateral knee, the pre-UKA knee was more adducted (p ≤ 0.019), and more laterally translated (p ≤ 0.008) during all four activities. Additionally, compared to contralateral knee, pre-UKA knee was less internally rotated (p ≤ 0.044) during chair rise and stair ascent. Lateral compartment dynamic joint space did not change during any activity from pre to post mUKA. Our results indicate that mUKA generally restores native kinematics during activities of daily living without altering lateral compartment dynamic joint space., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Robot-assisted surgical systems can predict post-operative kinematics based upon intra-operative passive kinematics, planned implant position and alignment, and soft-tissue tension. It is currently unknown how well the intra-operative passive kinematics replicate the post-surgical weight bearing active kinematics. This study compared intra-operative and post-operative tibiofemoral implant contact paths after medial unicompartmental knee arthroplasty (mUKA). Passive intraoperative and active postoperative tibiofemoral contact path data was collected from eight patients who underwent mUKA. Intraoperative contact path data was measured using a navigation system. Postoperative contact path data was measured during walking, chair rise, stair ascent, and stair descent using a biplane radiography system and a validated tracking process. A total of 86 movement trials were included in the analysis. The contact point on the femur implant was up to 9.8 mm more medial and up to 8.3 mm less anterior at low flexion angles during activities of daily living than during passive extension intra-operatively, and the contact point on the tibia implant was up to 13.8 mm less lateral and up to 5.8 mm less posterior at low flexion angles during activities of daily living than during intra-operative passive extension. Femoral contact paths primarily differed between 3° and 42° of flexion; and tibial contact paths differed between 3° and 50° of flexion. This pilot study is the first to compare intra-operative and post-operative weight bearing contact paths. The primary conclusions from this study are that contact points on the femur implant are more medial and less anterior at low flexion angles during activities of daily living than during passive extension intra-operatively, and that the contact points on the tibia implant are less lateral at low flexion angles during activities of daily living than during intra-operative passive extension., Competing Interests: Declaration of Competing Interest All authors must disclose any financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (Copyright © 2022 IPEM. Published by Elsevier Ltd. All rights reserved.)

This research investigated the performance of the red, octagonal Vienna Convention traffic 'STOP' sign as a front of pack (FoP) warning nutritional label. While the Vienna Convention traffic light system is an established FoP label, the potential of the 'STOP' sign in the role has not been investigated. The performance of the 'STOP' label was compared with that of a single star (low nutritional value) Australasian Health Star Rating (HSR) label using a fractionally replicated Latin square design. The labels were presented on choice diads of cold breakfast cereal packets. The sample of 240 adolescents aged 16-18 was drawn from a secondary school in the South Island of New Zealand. A large and significant main effect was observed at the p < 0.01 level for the difference between the 'STOP' sign and the control condition (no nutritional FoP label), and at p < 0.05 for the difference between the HSR and the 'STOP' label. There was no significant difference between the HSR FoP and the control condition. A significant non-additivity (interaction) ( p < 0.01) was also observed via the fractional replication. The results indicate that the Vienna Convention 'STOP' sign is worthy of further research with regard to its potential as an FoP nutritional label.

Background: Total knee arthroplasty (TKA) periprosthetic joint infection (PJI) can be managed with debridement, antibiotic therapy, and implant retention (DAIR). Oral antibiotics can be used after DAIR for an extended time period to improve outcomes. The objective of this study was to compare DAIR failure rates and adverse events between an initial course of intravenous antibiotic therapy and the addition of extended treatment with oral antibiotics., Methods: A multicenter observational study of patients diagnosed with a TKA PJI who underwent DAIR was performed. The primary outcome of interest was the failure rate derived from the survival time between the DAIR procedure and future treatment failure., Results: One hundred eight patients met inclusion criteria; 47% (n = 51) received an extended course of oral antibiotics. These patients had a statistically significant lower failure rate compared to those who received only intravenous antibiotics (hazard ratio, 2.47; P = .009). Multivariable analysis demonstrated that extended antibiotics independently predicted treatment success, controlling for other variables. There was no significant difference in failure rates between an extended course of oral antibiotics less or more than 12 months (P = .23). No significant difference in the rates of adverse events was observed between patients who received an initial course of antibiotics alone and those who received a combination of initial and extended antibiotic therapy (P = .59)., Conclusions: Extending therapy with oral antibiotics had superior infection-free survival for TKA PJI managed with DAIR. There was no increase in adverse events, demonstrating safety. After 1 year, there appears to be no significant benefit associated with continued antibiotic therapy., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Quality measures play a prominent role in the US health care system. They are used to monitor and report performance across health plans, providers, and health systems and are a foundational element of value-based payment. Measuring the quality of asthma care has been challenging because of a lack of reliable data to assess clinical processes and track patient-specific outcomes. Existing asthma Healthcare Effectiveness Data and Information Set measures rely on administrative claims-derived data on dispensed medications. These are proxy measures of appropriate prescribing but are not reflective of comprehensive asthma care. The increase in the volume and specificity of longitudinal clinical data in electronic health records, movement toward electronic quality measures, and advances in electronic clinical data systems enable the development of more meaningful measures. A patient-reported measure of asthma control would incorporate key clinical indicators such as a validated age- and culturally appropriate test, and would reflect the combined outcome of medical management, self-management education, reduction of environmental exposures, and appropriate support services. Although there is a current quality measure that includes a test of asthma control (the Optimal Asthma Control Measure), work is needed to address questions about usability, patient literacy, and the influence of setting on self-reported scores. Comprehensive reliability and validity testing of both clinical data and stratification across risk groups will be needed to determine whether a measure based on standardized assessments of asthma control indeed promote improved clinical outcomes., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Surgical navigation has been shown to improve the accuracy of bone preparation and limb alignment in total knee arthroplasty (TKA). Previous work has shown the effectiveness of various types of navigation systems. Here, for the first time, we assessed the accuracy of a novel imageless semiautonomous handheld robotic sculpting system in performing bone resection and preparation in TKA using cadaveric specimens. In this study, we compared the planned and final implant placement in 18 cadaveric specimens undergoing TKA using the new tool. Eight surgeons carried out the procedures using three types of implant designs. A quantitative analysis was performed to determine the translational, angular, and rotational differences between the planned and achieved positions of the implants. The mean femoral flexion, varus/valgus, and rotational error was -2.0°, -0.1°, and -0.5°, respectively. The mean tibial posterior slope, and varus/valgus error was -0.2°, and -0.2°, respectively. We obtained higher flexion errors for the femoral implant when using cut-guides as compared to using a bur for cutting the bones. The image-free robotic sculpting tool achieved accurate implementation of the surgical plan with small errors in implant placement. Future studies will focus on determining how well the accurate implant placement translates into a clinical and functional benefit for the patient.

Unicondylar Knee Arthroplasty (UKA) is a minimally-invasive surgical procedure for treating isolated compartmental knee osteoarthritis. Accurate implant placement is crucial for a successful UKA procedure. Previous work has shown the improvement in UKA by using robotic systems. Here, we present the implant alignment accuracy of a hand-held robotic UKA system compared with a conventional manual UKA system for 12 cadaver specimens. Two surgeons carried out equal number of medial UKAs with robotic UKA on one knee and the manual UKA on the other knee. Preoperative and postoperative computed tomography (CT) scans were obtained for each cadaveric model. The final implant positions were identified in the postoperative CT scan. The implant orientations were compared with the planned implant positions to obtain femoral and tibial implant alignment errors. Our results show that the femoral flexion, varus, and rotation root mean square errors for the robotic and conventional approach were 1.23°, 2.81°, 1.62° and 7.52°, 6.25°, 5.0°, respectively. The tibial slope and varus errors for the robotic and conventional approaches were 2.41°, 2.96° and 4.06°, 1.8°, respectively. We did not find any statistical significant difference (p = .05) in the performance of the two surgeons. We conclude that the hand-held robotic UKA system offers significant improvement in the final implant placement.

Background: Surgical robotics has been shown to improve the accuracy of bone preparation and soft tissue balance in unicondylar knee arthroplasty (UKA). However, although extensive data have emerged with regard to a CT scan-based haptically constrained robotic arm, little is known about the accuracy of a newer alternative, an imageless robotic system., Questions/purposes: We assessed the accuracy of a novel imageless semiautonomous freehand robotic sculpting system in performing bone resection and preparation in UKA using cadaveric specimens., Methods: In this controlled study, we compared the planned and final implant placement in 25 cadaveric specimens undergoing UKA using the new tool. A quantitative analysis was performed to determine the translational, angular, and rotational differences between the planned and achieved positions of the implants., Results: The femoral implant rotational mean error was 1.04° to 1.88° and mean translational error was 0.72 to 1.29 mm across the three planes. The tibial implant rotational mean error was 1.48° to 1.98° and the mean translational error was 0.79 to 1.27 mm across the three planes., Conclusions: The image-free robotic sculpting tool achieved accurate implementation of the surgical plan with small errors in implant placement. The next step will be to determine whether accurate implant placement translates into a clinical and functional benefit for the patient.

Noma (cancrum oris) is a disease of poverty and malnutrition, which predominantly affects children younger than 10 years in developing countries. Although the majority of sufferers die of sepsis at the time of the initial infection, or of subsequent starvation due to severe trismus and an inability to eat, a small minority of patients survive and require reconstructive surgery for severe facial scarring and deformity. These patients present significant problems to the anesthesiologist with regard to airway management. We present a series of 26 patients undergoing primary and subsequent reconstructive surgery, with particular focus on airway management. We show that airway management, while challenging, can be performed safely and successfully by using individualized airway plans but may require advanced techniques and equipment. Traditional tests focusing on the anterior/superior airway are helpful in assessing patients with facial deformity due to noma.

We reviewed the results of all eighteen total knee arthroplasties that had been performed at the Mayo Clinic between 1974 and 1992 for the treatment of pigmented villonodular synovitis. The diagnosis had been confirmed histologically in all patients. Fourteen patients had diffuse disease, which was active in eleven and inactive in three, and four had focal disease. In addition to the arthroplasty, the eleven patients who had active diffuse disease were managed with a complete synovectomy and the four patients who had focal disease had a partial synovectomy. The three remaining patients had a history of diffuse pigmented villonodular synovitis but had no evidence of disease at the time of the arthroplasty, so a synovectomy was not performed. At an average of 9.9 years (range, 3.6 to 20.1 years) after the arthroplasty, fourteen of the eighteen total knee prostheses were well fixed and functioning satisfactorily. The average knee score was 89 points (range, 80 to 99 points) and the average functional score was 77 points (range, 20 to 100 points) for these fourteen patients. The four failures were in patients who had active diffuse disease at the time of the arthroplasty. Three of the failures were due to aseptic loosening, and one was due to recurrence of the disease. Sixteen patients had no evidence of recurrence when they were last seen, at an average of 10.3 years (range, 3.6 to 20.1 years) after the arthroplasty. The two patients who had a recurrence were among the eleven who had active diffuse disease. In one of these patients, the recurrence was diagnosed at the time of a revision arthroplasty performed because of aseptic loosening. The other patient had two recurrences, necessitating an above-the-knee amputation.

We have developed a PCR-based method, called methylation-sensitive restriction fingerprinting (MSRF), to screen changes in DNA methylation in breast carcinomas. Two hypermethylation-containing fragments, HBC-1 (for "hypermethylation in breast cancer") and HBC-2, were identified in the amplified breast tumor DNA relative to the amplified normal breast DNA of a patient. Nucleotide sequence analysis revealed no significant matches between the sequence of HBC-1 and the known sequences in the GenBank database, whereas the sequence of HBC-2 matched the upstream region of an antisense WT1 (Wilms' tumor suppressor gene) promoter. The methylation status in the breast tumor DNA from this patient was confirmed by Southern hybridization using HBC-1 and HBC-2 as probes, respectively. Further analysis showed that HBC-1 was methylated aberrantly in 90% (17 of 19 patients) of the primary breast carcinomas examined. This study demonstrates that MSRF provides a useful means for screening aberrant changes in DNA methylation during tumorigenesis. The commonly methylated fragments identified by MSRF could potentially supplement pathological markers currently used for cancers and additionally lead to the discovery of novel methylated tumor suppressor genes.