Successful Reduction Research Articles

Percutaneous paravalvular leak closure after transcatheter aortic valve implantation: the international PLUGinTAVI Registry.

Data regarding the safety and long-term effectiveness of percutaneous closure of paravalvular leak (PVL) after transcatheter aortic valve implantation (TAVI) are scarce. This study aims to present alarge multicentre international experience of percutaneous post-TAVI PVL closure. All patients who underwent percutaneous post-TAVI PVL closure in 14 hospitals across Europe and North America between January 2018 and October 2022 were included. Overall, 45 patients (64% male) were enrolled. The median age was 80 years (75-84). Among them, 67% and 33% had self-expanding and balloon-expandable valve implantations, respectively. Baseline post-TAVI PVL was severe in 67% of cases and moderate in the rest. The time from index TAVI to PVL closure procedure was 16.1 (8.7-34.8) months. Most patients were in NYHA Class III and IV (73%) before the procedure, and 40% had referred hospitalisations for heart failure between TAVI and the PVL closure procedure. Successful PVL closure was achieved in 94%, reducing regurgitation to ≤mild in 91% and moderate in the rest. The Amplatzer Valvular Plug III was the most frequently used device (27 cases), followed by the Amplatzer Valvular Plug 4. The incidence of severe adverse events was 11%. None of the patients died during the index hospitalisation. During long-term follow-up (21.7±16.2 months), the all-cause mortality rate was 14%, and patients presented improvement in functional status and asignificant reduction in the rate of hospitalisation for heart failure (from 40% to 6%). Percutaneous PVL closure is afeasible and safe option for treating post-TAVI leaks. Successful PVL reduction to mild or less could be associated with acute and long-lasting improvements in clinical outcomes.

Excellent catalytic activity of NiPd/C nanocatalysts for anodic oxidation of methanol in alkaline media

In this study, nanocatalyst NiPd was synthesized via a successful two-stage reduction process with NaBH4 and PVP. More specifically, the first stage involves NaBH4 reduction of Ni2+ ion to metallic Ni. Afterwards, Pd would be coated on the surface of the aformentioned Ni particles by reducing Pd2+ using the remaining NaBH4. The effect of experimental parameters on the synthesis and catalytic activity of the nanocatalysts, such as reaction temperature (30, 40, 50, 60, 70 °C), reaction time (60, 90, 120, 150, 180 minutes), Pd:Ni mole ratio (1:10, 3:10, 5:10, 7:10, 9:10). were investigated by X-ray diffraction (XRD), Energy dispersive spectroscopy (EDX), and transmission electron microscopy (TEM) were used to analyse the surface structure, composition and morphology of the catalyst samples. The catalytic activity and stability of the resulting NiPd/C catalysts were investigated towards the methanol oxidation reaction (MOR) in alkaline environment by cyclic voltammetry (CV) and chronoamperometry (CA) techniques. The results showed that the highest catalytic activity was found for the sample synthesized at 50 °C with 120-minute reaction time and the Pd:Ni molar ratio of 5:10. The influence of KOH and methanol concentrations on the catalytic activity of NiPd/C for methanol oxidation reaction in alkaline medium was also investigated. The results demonstrated the promising potential of NiPd/C nanomaterials as catalyst materials for the anodic layer in direct methanol fuel cells (DMFCs).

A CLINICAL STUDY OF INTUSSUSCEPTION IN CHILDREN

A CLINICAL STUDY OF INTUSSUSCEPTION IN CHILDREN

Preformulation and Long-Term Stability Studies of an Optimized Palatable Praziquantel Ethanol-Free Solution for Pediatric Delivery.

To date, the treatment for cysticercosis and neurocysticercosis consists of a single oral intake of praziquantel (5-10 mg/kg), which since it is only available as tablets, hinders its administration to pediatric patients. Praziquantel is a poorly water-soluble drug which represents a challenge for its formulation in solution, particularly for the pediatric population. Thus, this study aimed to develop a palatable solution for praziquantel using pharmaceutical-accepted co-solvent systems. A design of experiments approach was applied to identify the optimal conditions for achieving a suitable amount of praziquantel in solution using co-solvent mixtures. Thus, praziquantel solubility increased from 0.38 up to 43.50 mg/mL in the optimized system. A taste masking assay in healthy human volunteers confirmed a successful reduction of drug bitterness after the addition of selected flavors and a sweetener. Stability studies were also conducted at different temperatures (4, 25, and 40 °C) for 12 months Even though the presence of the three known impurities of praziquantel was observed, their amounts never exceeded the acceptance criteria of the USP. Thus, this novel approach should be considered a valuable alternative for further preclinical studies considering the high prevalence of this infection worldwide.

Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma.

The goal of therapy in pediatric Hodgkin lymphoma (HL) is to maximize overall survival while minimizing the morbidity of curative therapy. Key findings from recent Children's Oncology Group (COG) trials include: (i) superior event-free survival with the addition of brentuximab vedotin (Bv) in frontline regimens for high-risk disease, (ii) successful reduction in myeloablative regimens with demonstrated safety and efficacy of Bv and checkpoint inhibitor therapy in relapsed disease, and (ii) the potential to select a population that can be salvaged after relapse without receiving a stem cell transplant. The COG HL committee will lead a National cancer Institute National Clinical Trials Network phase 3 trial to evaluate the combination of Bv/nivolumab in early-stage disease. Ongoing advances in technology and blood biomarkers are increasing the ability to deliver biologically driven, personalized treatment for HL.

When to Combine Acetabular Osteotomy in Patients With Proximal Femoral Deformity Causing Residual Hip Dysplasia/Subluxation After Reduction of Developmental Dysplasia of the Hip.

After the successful reduction of developmental dysplasia of the hip, residual hip dysplasia may persist and lead to early osteoarthritis. Femoral and/or acetabular osteotomy has been used to address this problem. The purpose of this study is to determine the indication of femoral versus combined femoral-acetabular osteotomy in the management of residual hip dysplasia. Fifty-five patients with unilateral dislocated-type dysplasia of the hip, who had residual hip dysplasia after reduction, underwent femoral osteotomy with or without acetabular osteotomy before 8 years of age, and were followed for more than 2 years and over 8 years of age, were the subjects of this retrospective study. Twenty-eight patients underwent femoral osteotomy only at a median age of 34 months (group F), and 27 underwent combined femoral-Dega osteotomy at a median age of 49 months (group C). Seventeen patients in group F and 4 in group C had an additional osteotomy due to persistent hip dysplasia. Acetabular index (AI), lateral center-edge angle, and center-head distance difference were measured on serial radiographs. The z-value of AI (Z AI ) was calculated. At the latest follow-up, patients in group F with Severin I/II who did not have an additional osteotomy were considered satisfactory, and patients with Severin III/IV or those who had an additional osteotomy were considered unsatisfactory. Preoperative variables were tested for the difference between satisfactory and unsatisfactory cases. Receiver operating characteristic analysis was performed to delineate a cutoff value of a significant parameter dividing the outcome. AI and Z AI before index osteotomy were significant parameters predicting a satisfactory outcome in group F. Receiver operating characteristic analysis returned a cutoff value of Z AI 2.6 (Area Under the Curve=0.86, P =0.001). Eight of 12 cases (66.7%) with Z AI <2.6 in group F achieved a satisfactory outcome, whereas only 2 of 14 cases with Z AI ≥2.6 in group F did ( P =0.02). Z AI 2.6 may serve as a threshold to combine acetabular osteotomy with femoral osteotomy in the management of residual hip dysplasia before 8 years of age. Therapeutic III.

TOPOLOGY OPTIMIZATION OF A HANGER FOR THE CRANE OF A BOAT

Topology optimization is the process of optimizing the shape and material distribution of a part. This study examines the topology optimization of the hanging apparatus of a boat's crane. The goal here is to design a lighter and more efficient hanging apparatus. Initially, topology optimization was performed using a CAD software such as Autodesk Fusion 360. This software aids engineers in creating complex designs, simulating real-world scenarios, and optimizing material distribution. The design process began with the use of a non-equilateral triangle to determine the shape of the part. Later, two cylindrical rings that attach to the pole were added. These steps completed the initial geometry. Subsequently, it was indicated that the part needed to be light and resistant to weather conditions. Therefore, aluminum 6061 material was chosen. The material properties were chosen to ensure the proper functioning of the part. A static analysis was performed to determine the strength of the part. The forces and constraints applied to the part were simulated considering a one-ton capacity. A displacement of 1.32 millimeters and a safety factor of 6 were found. Then, following the topology optimization, an analysis of the new geometry resulted in a displacement of approximately 4 millimeters for the part. The predetermined minimum safety factor is 3, and the factor found in the analysis was 3.7. This is an acceptable value to ensure the structural integrity and safety of the part. The optimization process aimed to reduce the mass of the part. By preserving the initially determined safety factor, savings were made in the material and a successful reduction of approximately 42% in mass was achieved. This study demonstrates that topology optimization is a significant tool in engineering design and CAD software such as Autodesk Fusion 360 can be effectively used in this process. The analyses and optimizations conducted reveal that it's possible to design a lighter and more efficient hanging apparatus. This provides numerous advantages such as cost savings, performance increase, and reduction of environmental impact.

Remodeling of the Drone Chassis Designed for Additive Manufacturing Method According to Topology Optimization

In the last few years, additive manufacturing methods have made remarkable advancements, and with the emergence of next-generation additive manufacturing techniques, the variety of raw materials has increased, and part design criteria have been improved. Particularly, the development of metal additive methods has made revolutionary contributions to the manufacturing field and offered a new and unique perspective on design. While traditional manufacturing methods require adherence to specific and standardized design criteria, there are no rules or standards that must be followed in additive manufacturing, except for a few criteria. This is one of the most significant features that distinguishes additive manufacturing methods from traditional methods. The freedom of design provided by additive manufacturing enables much more successful mass reduction in the parts produced using these methods. Mass reduction is expected to be minimal in aerospace, automotive, medical, and dental applications. In this study, first, a drone chassis was designed using NX software, and static analysis was performed in Ansys program by defining specific boundary conditions for the designed drone chassis. Then, based on the conducted static analysis, topology optimization was carried out in Ansys program to achieve mass reduction. As a result of the topology optimization performed, it was observed that the obtained geometry decreased from 5.8394 kg to 1.288 kg. After the topology optimization, the obtained geometry was redesigned in the NX environment, and static analysis was applied to the redesigned geometry. Considering the results of the applied static analysis, it was observed that the part can operate safely under working conditions. It was determined that the mass was reduced by approximately 78% after topology optimization, indicating that topology optimization was highly successful in the mass reduction process.

Antibacterial and Antibiofilm Activity of Ficus carica-Mediated Calcium Oxide (CaONPs) Phyto-Nanoparticles.

The significance of nanomaterials in biomedicines served as the inspiration for the design of this study. In this particular investigation, we carried out the biosynthesis of calcium oxide nanoparticles (CaONPs) by employing a green-chemistry strategy and making use of an extract of Ficus carica (an edible fruit) as a capping and reducing agent. There is a dire need for new antimicrobial agents due to the alarming rise in antibiotic resistance. Nanoparticles' diverse antibacterial properties suggest that they might be standard alternatives to antimicrobial drugs in the future. We describe herein the use of a Ficus carica extract as a capping and reducing agent in the phyto-mediated synthesis of CaONPs for the evaluation of their antimicrobial properties. The phyto-mediated synthesis of NPs is considered a reliable approach due to its high yield, stability, non-toxicity, cost-effectiveness and eco-friendliness. The CaONPs were physiochemically characterized by UV-visible spectroscopy, energy-dispersive X-ray (EDX), scanning-electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). The biological synthesis of the calcium oxide nanoparticles revealed a characteristic surface plasmon resonance peak (SPR) at 360 nm in UV-Vis spectroscopy, which clearly revealed the successful reduction of the Ca2+ ions to Ca0 nanoparticles. The characteristic FTIR peak seen at 767 cm-1 corresponded to Ca-O bond stretching and, thus, confirmed the biosynthesis of the CaONPs, while the scanning-electron micrographs revealed near-CaO aggregates with an average diameter of 84.87 ± 2.0 nm. The antibacterial and anti-biofilm analysis of the CaONPs showed inhibition of bacteria in the following order: P. aeruginosa (28 ± 1.0) > S. aureus (23 ± 0.3) > K. pneumoniae (18 ± 0.9) > P. vulgaris (13 ± 1.6) > E. coli (11 ± 0.5) mm. The CaONPs were shown to considerably inhibit biofilm formation, providing strong evidence for their major antibacterial activity. It is concluded that this straightforward environmentally friendly method is capable of synthesizing stable and effective CaONPs. The therapeutic value of CaONPs is indicated by their potential as a antibacterial and antibiofilm agents in future medications.

Green synthesis of reduced graphene oxide with multiple environmental applications

A sustainable and greener approach to synthesis of reduced graphene oxide (rGO) from graphene oxide (GO) was attempted using Bougainvillea Glabra (BVG) flower extract as a simple and eco-environmental friendly method. BVG flower extract exhibited antioxidant potential for FRAP/ ABTS assay [(731.53 mmol of Fe2+equivalents)/(56.64 mmol of Trolox equivalents)] with the anthocyanin content as 64 mg L−1. The reduction of GO to rGO was confirmed by various characterization techniques such as FTIR, Raman spectroscopy, PXRD, UV-vis absorption spectroscopy, SEM-EDS, TEM, UV-DRS, BET and ZP analysis. SEM-EDS and HR-TEM analysis revealed the stacked, smooth and layered structure of rGO with increasing atomic wt. % of carbon and reduction in oxygen as per the EDS spectra, which confirmed the successful reduction of GO. Comparative photocatalytic degradation of organic pollutants under similar experimental condition using BVG modified rGO was found to be as follows: MB (81.06%) > RhB (75.84%) > MO (57.42%) > SA (48.18%) and was higher than that of GO. Likewise, rGO exhibited higher antibacterial effect against two different Gram positive bacteria (Staphylococcus Aureus and Listeria monocytogenes) followed by two different Gram negative bacteria (Salmonella Enterica typhimurium and Escherichia coli) than GO under optimized catalyst dose (50 mg) and bacterial culture concentration (1.5 × 108 CFU/mL). Thus, rGO synthesized using this green approach, could be beneficial for tertiary wastewater treatment to remove the residual pollutants as well as the bacterial pathogens and can act as an effective and greener alternative over other commonly available catalyst.

The Weighted Toxicity Score: Confirmation of a Simple Metric to Communicate Toxicity in Randomized Trials of Systemic Cancer Therapy.

FDA's Project Optimus was developed in part to better identify appropriate dose and schedule of cancer therapeutics. The tabular method to summarize patients' maximum toxicity in a clinical trial does not allow for ready comparison to the treatment's benefit. In this manuscript, we apply a simple tool, the weighted toxicity score (WTS), to trials involving lung cancer immunotherapy and chemotherapy, as well as those cited in a recent publication as examples of trials that represent successful reduction of the appropriate dose of anti-cancer agents. PubMed was queried for randomized controlled trials of therapy involving immune checkpoint inhibitors in lung cancer. Trial data from studies highlighting initial success with dose adjustments after FDA approval also were assembled and analyzed according to the WTS procedure described previously, compared to clinical outcomes data. The WTS provided, with the clinical outcome(s), a data pair that leads to easy interpretation of the expected benefit versus relative toxicity of studies involving immunotherapy or chemoimmunotherapy in lung cancers. The WTS was consistent with the conclusions of the primary studies, helping to quantitate the toxicity difference between treatments in a previously unavailable way. The WTS provides a tool to show the cost in toxicity of therapy in a randomized clinical trial, with applicability to studies involving chemotherapy, immunotherapy, or kinase-directed therapy. Inclusion of a running tally of WTS during conduct of a trial could serve as one means to adjust dosing or to provide feedback during data safety monitoring of a clinical trial.

Balancing immunosuppression in pediatric liver transplantation: Playing the long game.

The overarching goal in the care of pediatric liver transplant recipients is to optimize allograft and patient health. Balancing immunosuppression to maintain allograft health while avoiding medication side effects is essential for long-term survival and optimal quality of life in pediatric liver transplant recipients. Utilizing precision medicine to personalize immunosuppression, which includes minimization and withdrawal, is core to this effort. The unique anatomy and physiology of the liver make it more tolerant to immune-mediated injury and a more favorable organ for immunosuppression minimization and withdrawal. However, several challenges exist. Standard biochemical values and histologic features may not reliably predict allograft health after a reduction in immunosuppression. Additionally, biochemical values alone do not reliably identify which patients can successfully develop operational tolerance, as there may be occult allograft injury despite normal liver enzymes. Finally, the durability of tolerance after successful reduction in immunosuppression remains uncertain over time. Innovative tools show promise in circumventing these challenges, but more research is needed to determine actual clinical utility. While immunosuppression-free transplant may not be a current reality for most pediatric liver transplant recipients, strategies to safely minimize immunosuppression without compromising allograft health are within reach. Each liver allograft and recipient pair requires a different degree of immune modulation, and through a structured process of minimization and withdrawal, immunosuppression can indeed be tailored in a precise, personalized way to optimize outcomes. This review focuses on the progress that has been made to individualize immunosuppression in pediatric liver transplantation to ensure optimal allograft and recipient health.

Non-parametric optimization for lightweight and high heat conductive structures under convection using metaheuristic structure binary-distribution method

In this paper, we propose a novel Metaheuristic Structure Binary-Distribution (MSB) method for attaining lightweight and high thermal conductive structure. MSB combines metaheuristic search with gradient descent optimization, offering a robust and efficient approach. The paper also introduces a connectivity filtering approach to enhance additive manufacturability and eliminate segregated materials in thermal structures, improving integrity and minimizing materials wastage. The performance of the MSB method is compared to other topology optimization methods, namely bi-directional evolutionary structural optimization (BESO), solid isotropic materials with penalization (SIMP), and the parametrized level set method (PLSM). Results consistently demonstrate the better performance of MSB in weight reduction and minimizing thermal compliance. Even at significant weight reductions (50%, 60%, and 70%), MSB outperforms other methods, achieving lower thermal compliance. Investigations on mesh impact and the effectiveness of MSB with suggested connectivity filtering show a successful reduction of islands to solid elements to 0%, improving additive manufacturability and decreasing thermal compliance. The feasibility and suitability of the optimized designs for additive manufacturing are validated through 3D printing, confirming the practicality of the MSB method.

Iron reduction as a viable metabolic pathway in Enceladus’ ocean

AbstractRecent studies postulated the viability of a suite of metabolic pathways in Enceladus’ ocean motivated by the detection of H2 and CO2 in the plumes – evidence for available free energy for methanogenesis driven by hydrothermal activity at the moon's seafloor. However, these have not yet been explored in detail. Here, a range of experiments were performed to investigate whether microbial iron reduction could be a viable metabolic pathway in the ocean by iron-reducing bacteria such as Geobacter sulfurreducens. This study has three main outcomes: (i) the successful reduction of a number of crystalline Fe(III)-bearing minerals predicted to be present at Enceladus was shown to take place to differing extents using acetate as an electron donor; (ii) substantial bacterial growth in a simulated Enceladus ocean medium was demonstrated using acetate and H2(g) separately as electron donors; (iii) microbial iron reduction of ferrihydrite was shown to partially occur at pH 9, the currently accepted value for Enceladus’ ocean, whilst being severely hindered at the ambient ocean temperature of 0°. This study proposes the possibilities for biogeochemical iron cycling in Enceladus’ ocean, suggesting that a strain of iron-reducing bacteria can effectively function under Enceladus-like conditions.

Patient Safety Program in Emergency Department (ED) at Prof. Dr. Chairuddin Panusunan Lubis Hospital in 2023

This research explores the implementation of patient safety goals in the Emergency Department (ED) of Prof. Dr. Chairuddin Panusunan Lubis Hospital in 2022. Qualitative data gathered from key informants, including the Head of the ED, Head Nurse, and staff nurses, reveals determinants impacting patient safety. The study identifies several findings: good patient identification, the need for improved communication, positive progress in medication safety, effective implementation of site marking, successful reduction of infection risk, and adequate measures to minimize patient falls. Recommendations include enhancing communication among nurses and reinforcing medication safety protocols. The systematic application of site marking ensures precise location and procedures. Efforts to reduce infection risk and prevent patient falls are commendable, supported by appropriate policies, procedures, and training programs

Concurrent application of bacterial-mediated and mycosynthesized ZnO nanofungicides to maintain high ascorbic acid and delay postharvest decay of apricot

Quality of apricot fruit is affected by different biotic stresses during growth, harvesting and storage. Due to fungal attack, huge losses of its quality and quantity are observed. The present research was designed for the diagnoses and management of postharvest rot disease of apricot. Infected apricot fruit were collected, and the causative agent was identified as A. tubingensis. To control this disease, both bacterial-mediated nanoparticles (b-ZnO NPs) and mycosynthesized nanoparticles (f-ZnO NPs) were used. Herein, biomass filtrates of one selected fungus (Trichoderma harzianum) and one bacterium (Bacillus safensis) were used to reduce zinc acetate into ZnO NPs. The physiochemical and morphological characters of both types of NPs were determined. UV–vis spectroscopy displayed absorption peaks of f-ZnO NPs and b-ZnO NPs at 310–380 nm, respectively, indicating successful reduction of Zinc acetate by the metabolites of both fungus and bacteria. Fourier transform infrared (FTIR) determined the presence of organic compounds like amines, aromatics, alkenes and alkyl halides, on both types of NPs, while X-ray diffraction (XRD) confirmed nano-size of f-ZnO NPs (30 nm) and b-ZnO NPs (35 nm). Scanning electron microscopy showed flower-crystalline shape for b-ZnO NPs and spherical-crystalline shape for f-ZnO NPs. Both NPs showed variable antifungal activities at four different concentrations (0.25, 0.50, 0.75 and 1.00 mg/ml). Diseases control and postharvest changes in apricot fruit were analyzed for 15 days. Among all treatments, 0.50 mg/ml concentration of f-ZnO NPs and 0.75 mg/ml concentration of b-ZnO NPs exhibited the strongest antifungal activity. Comparatively, f-ZnO NPs performed slightly better than b-ZnO NPs. Application of both NPs reduced fruit decay and weight, maintained higher ascorbic acid contents, sustained titratable acidity, and preserved firmness of diseased fruit. Our results suggest that microbial synthesized ZnO NPs can efficiently control fruit rot, extend shelf life, and preserve the quality of apricot.

Predictors of Residual Severe Tricuspid Regurgitation After Transcatheter Mitral Valve Repair.

Severe tricuspid regurgitation (TR) may persist after a mitral transcatheter edge-to-edge repair (M-TEER) and is associated with worsened clinical outcomes and survival. It is unclear which patients with concomitant mitral regurgitation (MR) and TR will have TR reduction after M-TEER. The aim of this study was to identify the predictors of residual TR after transcatheter edge-to-edge repair (TEER). Data were collected from the Northwell TEER registry, a prospectively maintained mandatory database including 4 high-volume transcatheter aortic valve replacement/TEER centers. Transthoracic echocardiograms, both pre-TEER and post-TEER, were evaluated. Univariate and multivariate logistic regression analyses were performed to identify predictors of severe TR after M-TEER. Significant TR reduction was defined as a reduction in TR grade by at least 1+ with moderate (2+) or less TR at 1 month. Of the 479 patients who underwent M-TEER, 107 patients with concomitant severe MR/TR were included. Successful MR reduction occurred in 89 patients (84%) and a significant TR reduction in 45 (42%). On the univariate analysis, the only predictors of severe residual TR were right atrial area and unsuccessful M-TEER. On the multivariate logistic regression model, the only predictor variable for patients with a reduction in TR was MR reduction of ≥3+ with M-TEER. In patients with concomitant severe MR and TR, TR reduction after isolated M-TEER occurs in only ∼40% of patients. MR grade reduction ≥3+ was the only independent predictor for TR reduction. Other clinical and echocardiographic variables (including pulmonary hypertension, right ventricular function, tricuspid annular dilation, atrial fibrillation, and presence of a cardiac implantable electrical device) were not associated with residual TR. Inability to predict TR reduction after M-TEER highlights the importance of establishing transcatheter tricuspid valve therapies and should factor in heart-team discussions.

Current approaches to preventing heart failure readmissions and decompensated disease.

Heart failure is a resource-intensive condition to manage and typically involves a multi-disciplinary and multi-modality approach leading to an expensive treatment paradigm. It is worth noting that hospital admissions constitute over 80% of heart failure management costs. In the past two decades, healthcare systems have developed new ways of following patients remotely to prevent them from being readmitted to the hospital. However, despite these efforts, hospital admissions have still increased. Many successful readmission reduction programs prioritize education and self-care to increase patients' awareness of their disease and promote lasting lifestyle changes. While socioeconomic factors impact success, interventions tend to be effective when medication adherence and guideline-directed medical therapy are emphasized. Monitoring intracardiac pressure can improve resource allocation efficiency and has demonstrated significant reductions in readmissions with improved quality of life in outpatient and remote settings. Data from several studies focused on remote monitoring devices strongly suggest that understanding congestion using physiological biomarkers is an effective management strategy. Since most cases of heart failure are first presented in acute hospitalization settings, immediate access to intracardiac pressure for treatment and decision-making purposes could result in substantial management improvements. However, a notable technology gap needs to be addressed to enable this at a low cost with less reliability on scarce specialist care resources. Contemporary evidence is conclusive that direct hemodynamic are the vital signs in heart failure with the highest clinical utility. Therefore, future ability to obtain these insights reliably using non-invasive methods will be a paradigm-changing technology.

Use of Intraoperative Technology to Perform a Cam Resection During Hip Arthroscopy for Femoroacetabular Impingement Syndrome

Background: The learning curve for the surgical treatment of cam deformities in femoroacetabular impingement syndrome (FAIS) presents a challenge for young or inexperienced surgeons, with the leading cause of failed hip arthroscopy being incomplete resection. Historically, alpha angle measurements are typically used perioperatively to both diagnose cam deformity and evaluate the adequacy of cam resection. The computer-assisted Styker HipCheck system offers the surgeon real-time alpha angle measurements, assisting with the execution of cam resection. Indications: The indication for use is any hip arthroscopic procedure for femoroacetabular impingement requiring osteochondroplasty of cam deformity. Advantages of the HipCheck system include shortened operative time; reduced risk of inadequate or over-resection; accelerated learning curve; no requirement of preoperative computed tomographic imaging or pre-planning; being noninvasive, portable, and not requiring additional instruments; increased patient and surgeon satisfaction; and allowance of repeated quantitative and visual assessment, which is particularly beneficial for more difficult regions, such as posteromedial and posterolateral, to view the femoral head/neck. Technique Description: Briefly, after intra-articular procedures are complete, the peripheral compartment is accessed. We prefer a T-type capsulotomy. Next, the cam deformity is registered on Stryker HipCheck software, automatically calculating alpha angles as the hip is dynamically moved through 6 registered positions. A standard cam resection is then performed. Once complete, the hip is dynamically assessed and again registered with the HipCheck system in the same 6 positions to ensure adequate resection has been performed. Results: When comparing patients with FAIS undergoing computer-guided resection or standard resection, both surgical interventions demonstrated successful reduction in alpha angle and no difference in degree of resection. In addition, the various computer-guided views exhibited good correlations to clinical radiographs. Discussion: The HipCheck intraoperative system allows the surgeon to evaluate the adequacy of cam resection through the use of automated alpha angles. Furthermore, the system offers instantaneous feedback of cam resection at any desired position of the hip. This intraoperative technology may offer less experienced surgeons an aid when performing hip arthroscopy for cam resection in the setting of femoroacetabular impingement. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Identification and characterization of CYP71 subclade cytochrome P450 enzymes involved in the biosynthesis of bitterness compounds in Cichorium intybus.

Industrial chicory (Cichorium intybus var. sativum) and witloof (C. intybus var. foliosum) are crops with an important economic value, mainly cultivated for inulin production and as a leafy vegetable, respectively. Both crops are rich in nutritionally relevant specialized metabolites with beneficial effects for human health. However, their bitter taste, caused by the sesquiterpene lactones (SLs) produced in leaves and taproot, limits wider applications in the food industry. Changing the bitterness would thus create new opportunities with a great economic impact. Known genes encoding enzymes involved in the SL biosynthetic pathway are GERMACRENE A SYNTHASE (GAS), GERMACRENE A OXIDASE (GAO), COSTUNOLIDE SYNTHASE (COS) and KAUNIOLIDE SYNTHASE (KLS). In this study, we integrated genome and transcriptome mining to further unravel SL biosynthesis. We found that C. intybus SL biosynthesis is controlled by the phytohormone methyl jasmonate (MeJA). Gene family annotation and MeJA inducibility enabled the pinpointing of candidate genes related with the SL biosynthetic pathway. We specifically focused on members of subclade CYP71 of the cytochrome P450 family. We verified the biochemical activity of 14C. intybus CYP71 enzymes transiently produced in Nicotiana benthamiana and identified several functional paralogs for each of the GAO, COS and KLS genes, pointing to redundancy in and robustness of the SL biosynthetic pathway. Gene functionality was further analyzed using CRISPR/Cas9 genome editing in C. intybus. Metabolite profiling of mutant C. intybus lines demonstrated a successful reduction in SL metabolite production. Together, this study increases our insights into the C. intybus SL biosynthetic pathway and paves the way for the engineering of C. intybus bitterness.