Low implantation volume, comorbidities, male sex and implantation of constrained TKA identified as risk factors for septic revision in knee arthroplasty: A register-based study from the German Arthroplasty Registry.

PURPOSE: Periprosthetic joint infection (PJI) is a major cause of revision surgery after total knee arthroplasty (TKA) and unicondylar knee arthroplasty (UKA). Patient- and hospital-related risk factors need to be assessed to prevent PJI. This study identifies influential factors and differences in infection rates between different implant types. METHODS: Data were obtained from the German Arthroplasty Registry. Septic revisions were calculated using Kaplan-Meier estimates with septic revision surgery as the primary endpoint. Patients with constrained and unconstrained TKA or UKA were analysed using Holm's multiple log-rank test and Cox's proportional hazards ratio. The 300,998 cases of knee arthroplasty analysed included 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA with a maximum follow-up of 7 years. RESULTS: At 1 year, the PJI rate was 0.5% for UKA and 2.8% for TKA, whereas at 7 years, the PJI rate was 4.5% for UKA and 0.9% for TKA (p < 0.0001). The PJI rate significantly increased for constrained TKA compared to unconstrained TKA (p < 0.0001). The PJI rate was 2.0% for constrained TKA and 0.8% for unconstrained TKA at 1 year and 3.1% and 1.4% at 7 years. Implantation of a constrained TKA (hazard ratio [HR] = 2.55), male sex (HR = 1.84), increased Elixhauser score (HR = 1.18-1.56) and implant volume of less than 25 UKA per year (HR = 2.15) were identified as risk factors for revision surgery; an Elixhauser score of 0 (HR = 0.80) was found to be a preventive factor. CONCLUSIONS: Reduced implant volume and constrained knee arthroplasty are associated with a higher risk of PJI. Comorbidities (elevated Elixhauser score), male sex and low UKA implant volume have been identified as risk factors for PJI. Patients who meet these criteria require specific measures to prevent infection. Further research is required on the potential impact of prevention and risk factor modification. LEVEL OF EVIDENCE: Level III.

Unicondylar knee arthroplasty demonstrating a significant increased risk for aseptic revisions compared to unconstrained and constrained total knee arthroplasty: An analysis of aseptic revisions after unicondylar and primary total knee arthroplasty of the German Arthroplasty Registry.

PURPOSE: Due to ageing population, the implantation rate of total knee arthroplasties (TKAs) is continuously growing. Aseptic revisions in primary knee arthroplasty are a major cause of revision. The aim of the following study was to determinate the incidence and reasons of aseptic revisions in constrained and unconstrained TKA, as well as in unicondylar knee arthroplasties (UKAs). METHODS: Data collection was performed using the German Arthroplasty Registry. Reasons for aseptic revisions were calculated. Incidence and comparison of aseptic revisions were analysed using Kaplan-Meier estimates. A multiple χ2 test with Holm's method was used to detect group differences in ligament ruptures. RESULTS: Overall, 300,998 cases of knee arthroplasty with 254,144 (84.4%) unconstrained TKA, 9993 (3.3%) constrained TKA and 36,861 (12.3%) UKA were analysed. Aseptic revision rate in UKA was significantly increased compared to unconstrained and constrained TKA (p < 0.0001). In constrained TKA, a 2.0% revision rate for aseptic reasons were reported after 1 year, while in unconstrained TKA 1.1% and in UKA, 2.7% of revisions were identified. After 7 years in constrained TKA 3.3%, in unconstrained TKA 2.8%, and in UKA 7.8% sustained aseptic revision. Ligament instability was the leading cause of aseptic revision accounting for 13.7% in unconstrained TKA. In constrained TKA, 2.8% resulted in a revision due to ligament instability. In the UKA, the most frequent cause of revisions was tibial loosening, accounting for 14.6% of cases, while progression of osteoarthritis accounted for 7.9% of revisions. Ligament instability was observed in 14.1% of males compared to 15.9% of females in unconstrained TKA and in 4.6% in both genders in UKA. CONCLUSION: In patients with UKA, aseptic revision rates are significantly higher compared to unconstrained and constrained TKA. Ligament instability was the leading cause of aseptic revision in unconstrained TKA. In UKA, the most frequent cause of revisions was tibial loosening, while progression of osteoarthritis was the second most frequent cause of revisions. Comparable levels of ligament instability were observed in both sexes. LEVEL OF EVIDENCE: Level III, cohort study.

Sequential Sol-Gel Self-Assembly and Nonclassical Gel-Crystal Transformation of the Metal-Organic Framework Gel.

Metal-organic framework (MOF) gel, an emerging subtype of MOF structure, is unique in formation and function; however, its evolutionary process remains elusive. Here, the evolution of a model gel-based MOF, UiO-66(Zr) gel, is explored by demonstrating its sequential sol-gel self-assembly and nonclassical gel-crystal transformation. The control of the sol-gel process enables the observation and characterization of structures in each assembly stage (phase-separation, polycondensation, and hindered-crystallization) and facilitates the preparation of hierarchical materials with giant mesopores. The gelation mechanism is tentatively attributed to the formation of zirconium oligomers. By further utilizing the pre-synthesized gel, the nonclassical gel-crystal transformation is achieved by the modulation in an unconventional manner, which sheds light on crystal intermediates and distinct crystallization motions ("growth and splitting" and "aggregation and fusion"). The overall sol-gel and gel-crystal evolutions of UiO-66(Zr) enrich self-assembly and crystallization domains, inspire the design of functional structures, and demand more in-depth research on the intermediates in the future.

National survey on the availability of oncology palliative care services at tertiary general and cancer hospitals in China.

BACKGROUND: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China. METHODS: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service. RESULTS: Most responders reported that some type of PC service (possibly called "comprehensive cancer care," "pain and symptom management," or "supportive care") was available at their institution (84.3% of tertiary general hospitals, 82.8% of cancer hospitals). However, cancer hospitals were significantly more likely than tertiary general hospitals to have a PC department or specialist (34.1% vs. 15.5%, p < 0.001). The most popular services were pain consultation (> 92%), symptom management (> 77%), comprehensive care plans (~ 60%), obtaining advanced directives and do-not-resuscitate orders (~ 45%), referrals to hospice (> 32%), and psychiatric assessment (> 25%). Cancer hospitals were also more likely than tertiary general hospitals to report having inpatient beds for PC (46.3% vs. 30.5%; p = 0.010), outpatient PC clinics (28.0% vs. 16.8%; p = 0.029), educational programs (18.2% vs. 9.0%, p = 0.014), and research programs (17.2% vs. 9.3%, p < 0.001). CONCLUSIONS: Cancer hospitals are more likely to offer PC than are tertiary general hospitals in China. Our findings highlight opportunities to further increase the PC capacity in Chinese hospitals.

The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania.

BACKGROUND AND PURPOSE: Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). PATIENTS AND METHODS: This observational study is based on 2,971,357 primary TKAs reported in 2010-2020 to national/regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. RESULTS: ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). CONCLUSION: The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.

A Tiered Ecological Risk Assessment of Caffeine by Using Species Sensitivity Distribution Method in the Nansi Lake Basin.

Caffeine has been reported toxic to aquatic organisms, and it frequently occurs at relatively high concentrations in most of surface waters. However, it is difficult to control caffeine pollution because of the lack of Water Quality Criteria (WQC). In this study, species sensitivity distribution method and Log-normal model were applied to derive caffeine WQC as 83.7 ng/L. Meanwhile, concentrations of caffeine in the Nansi Lake basin were detected in 29 sampling sites, with the mean of 99.3 ng/L. The levels of caffeine in tributaries were higher than those in the lakes. In addition, a tied ecological risk assessment method was applied to assess the adverse effect of caffeine on aquatic system. The joint probability curve indicated that ecological risk might exist 3.1% of surface water in the study area, while 5% threshold (HC5) was set up to protect aquatic species. Generally, caffeine posted a low risk to aquatic organisms in the Nansi Lake basin.

Discovering Dynamic Plant Enzyme Complexes in Yeast for Kratom Alkaloid Pathway Identification.

Discovering natural product biosynthetic pathways of medicinal plants is challenging and laborious. Capturing the coregulation patterns of pathway enzymes, particularly transcriptomic regulation, has proven an effective method to accelerate pathway identification. In this study, we developed a yeast-based screening method to capture the protein-protein interactions (PPI) between plant enzymes, which is another useful pattern to complement the prevalent approach. Combining this method with plant multiomics analysis, we discovered four enzyme complexes and their organized pathways from kratom, an alkaloid-producing plant. The four pathway branches involved six enzymes, including a strictosidine synthase, a strictosidine ß-D-glucosidase (MsSGD), and four medium-chain dehydrogenase/reductases (MsMDRs). PPI screening selected six MsMDRs interacting with MsSGD from 20 candidates predicted by multiomics analysis. Four of the six MsMDRs were then characterized as functional, indicating the high selectivity of the PPI screening method. This study highlights the opportunity of leveraging post-translational regulation features to discover novel plant natural product biosynthetic pathways.

Thin-film lithium niobate polarization modulator without polarization diversity.

With the development of photonic integrated circuits and optical information processing on thin-film lithium niobate (TFLN), the realization of the TFLN-based polarization device is becoming more and more crucial. Here, we demonstrate a polarization modulator on the TFLN platform without polarization diversity. Without polarization manipulation elements, the device only composes a phase modulator and a two-dimensional grating coupler. The structure features small footprint and high fabrication tolerance. The device holds promise for polarization encoding telecommunication.

A case of ovarian Teratoma with nephroblastoma presenting abdomen metastasis.

BACKGROUND: Teratoma with nephroblastoma (TWN) is an extremely rare condition. Since 1984, only 45 reported cases have been identified. To our knowledge, there have been only two cases of TWN of ovarian origin. CASE PRESENTATION: We described a case of ovarian TWN who presented to us with painless abdominal masses 6 months after undergoing right ovarian cystectomy. The tumor had spread to the abdomen due to spontaneous rupture of the ovarian cyst and failure to undergo chemotherapy. Microscopically, the ovarian mass exhibited the typical components of a mature cystic teratoma. The tumors found in both the ovary and abdomen contained the nephroblastoma components and were strongly positive for WT-1. The patient was advised to undergo chemotherapy and she was lost to follow-up. CONCLUSION: A careful histological examination is necessary for an accurate diagnosis, which is based on morphology and extensive immunohistochemical studies. According to the literature, surgical excision alone seems reasonable as the prognosis of TWN is considered to be good. However, due to the spontaneous rupture of the ovarian cyst, chemotherapy of the patient after the first surgery was necessary in our case. Therefore, additional case studies are needed to clarify the standardized treatment of TWN.

Polygalaxanthone III, an Active Ingredient in Polygala japonica Houtt., Repaired Malassezia-Stimulated Skin Injury via STAT3 Phosphorylated Activation.

Malassezia is a genus of commensal and lipid-dependent yeasts in human skin which also have a pathogenic lifestyle associated with several common skin disorders such as atopic dermatitis and eczema. Symptoms include red, itchy, and inflamed skin. We studied the growth characteristics and biochemical analyses of M. furfur which showed that the protein contents were greater in extracts taken at 24 h. These were then used to infect C57BL/6 mice, resulting in skin rupture. Polygalaxanthone III (POL), a more effective anti-inflammatory ingredient in Polygala japonica Houtt., was applied externally to the ulceration and successfully healed the wounds quickly. POL could not inhibit Malassezia activity as tested by the inhibition zone test, but affected the formation of lipid droplets in HaCaT cells. The wound-healing molecular mechanisms may be involved in the STAT3 pathway according to the Western blot results of skin tissues. Malassezia's role in skin health is far from certain, and there is no clear solution, so understanding the development of Malassezia-associated skin diseases in general and seeking solutions are very important.

A Showcase of Green Chemistry: Sustainable Synthetic Approach of Zirconium-Based MOF Materials.

Zirconium-based metal-organic framework materials (Zr-MOFs) have more practical usage over most conventional benchmark porous materials and even many other MOFs due to the excellent structural stability, rich coordination forms, and various active sites. However, their mass-production and application are restricted by the high-cost raw materials, complex synthesis procedures, harsh reaction conditions, and unexpected environmental impact. Based on the principles of "Green Chemistry", considerable efforts have been done for breaking through the limitations, and significant progress has been made in the sustainable synthesis of Zr-MOFs over the past decade. In this review, the advancements of green raw materials and green synthesis methods in the synthesis of Zr-MOFs are reviewed, along with the corresponding drawbacks. The challenges and prospects are discussed and outlooked, expecting to provide guidance for the acceleration of the industrialization and commercialization of Zr-MOFs.

Design of Polymeric Thin Films to Direct Microbial Biofilm Growth, Virulence, and Metabolism.

Biofilms are ubiquitous in nature, yet strategies to direct biofilm behavior without genetic manipulation are limited. Due to the small selection of materials that have been used to successfully grow biofilms, the availability of functional materials that are able to support growth and program microbial functions remains a critical bottleneck in the design and deployment of functional yet safe microbes. Here, we report the design of insoluble pyridine-rich polymer surfaces synthesized using initiated chemical vapor deposition, which led to modulated biofilm growth and virulence in Pseudomonas aeruginosa (PAO1). A variety of extracellular virulence factors exhibited decreased production in response to the functional polymer, most significantly biomolecules also associated with iron acquisition, validating the material design strategy reported here. This report signifies a rich potential for materials-based strategies to direct the behavior of naturally occurring biofilms, which complement the existing genetic engineering toolkits in advancing microbiology, translational medicine, and biomanufacturing.

Single-Atom Fe Catalyst Outperforms Its Homogeneous Counterpart for Activating Peroxymonosulfate to Achieve Effective Degradation of Organic Contaminants.

Recently, reactive iron species (RFeS) have shown great potential for the selective degradation of emerging organic contaminants (EOCs). However, the rapid generation of RFeS for the selective and efficient degradation of EOCs over a wide pH range is still challenging. Herein, we constructed FeN4 structures on a carbon nanotube (CNT) to obtain single-atom catalysts (FeSA-N-CNT) to generate RFeS in the presence of peroxymonosulfate (PMS). The obtained FeSA-N-CNT/PMS system exhibited outstanding and selective reactivity for oxidizing EOCs over a wide pH range (3.0-9.0). Several lines of evidences suggested that RFeS existing as an FeN4═O intermediate was the predominant oxidant, while SO4·- and HO· were the secondary oxidants. Density functional theory calculation results revealed that a CNT played a key role in optimizing the distribution of bonding and antibonding states in the Fe 3d orbital, resulting in the outstanding ability of FeSA-N-CNT for PMS chemical adsorption and activation. Moreover, CNT could significantly enhance the reactivity of the FeN4═O intermediate by increasing the overlap of electrons of the Fe 3d orbital, O 2p orbital, and bisphenol A near the Fermi level. The results of this study can advance the understanding of RFeS generation in a heterogeneous system over a wide pH range and the application of RFeS in real practice.

Polygalaxanthone III downregulates inflammation in the lipopolysaccharide-stimulated RAW264.7 macrophages: A quantibody array analysis.

Polygala japonica Houtt. (PJ), a member of the Polygala L. family that is suggested to exhibit detoxification properties in traditional Chinese medicine, is often used to treat upper respiratory tract infections. The anti-inflammatory effects of four main components of PJ (POL, PS-XLIX, PS-E, and PS-F) were examined using the LPS(0.3 µg·mL-1)-stimulated RAW264.7 macrophage model. The levels of NO, ROS, and iNOS were examined to analyze the anti-inflammatory activity of POL. Additionally, the levels of extracellular inflammation-related cytokines and chemokines were measured using quantibody array. The KEGG pathway analysis was performed to examine the anti-inflammatory mechanism of POL. The levels of NO in the POL-pretreated group were significantly downregulated when compared with those in the PS-E-pretreated, PS-F-pretreated, and PS-XLIX-pretreated groups. POL significantly inhibited the changes of iNOS, ROS, and inflammatory factors caused by LPS stimulation (p < 0.001). The expression levels of IL21 and GM-CSF were examined using qPCR, while those of JAK-STAT signaling pathway-related proteins in the LPS-stimulated RAW264.7 macrophages were analyzed using western blotting. POL significantly downregulated the expression of IL-21 and GM-CSF. The anti-inflammatory mechanism of POL is mediated through the JAK-STAT pathway. Thus, this study demonstrated that POL is an anti-inflammatory component of PJ and elucidated its mechanism.

Retracted: Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9.

On Authors request due to not being able to reproduce the experiment. Reference: Yichen Fang, Jie Li, Yinan Wu, Jing Gui, Yang Shen. Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9. Med Sci Monit, 2019; 25: 3231-3237. DOI: 10.12659/MSM.914029.

Terpenoids from the Deep-Sea-Derived Fungus Penicillium thomii YPGA3 and Their Bioactivities.

A chemical study of the ethyl acetate (EtOAc) extract from the deep-sea-derived fungus Penicillium thomii YPGA3 led to the isolation of a new austalide meroterpenoid (1) and seven known analogues (28), two new labdane-type diterpenoids (9 and 10) and a known derivative (11). The structures of new compounds 1, 9, and 10 were determined by comprehensive analyses via nuclear magnetic resonance (NMR) and mass spectroscopy (MS) data. The absolute configurations of 1, 9, and 10 were determined by comparisons of experimental electronic circular dichroism (ECD) with the calculated ECD spectra. Compound 1 represented the third example of austalides bearing a hydroxyl group at C-5 instead of the conserved methoxy in other known analogues. To our knowledge, diterpenoids belonging to the labdane-type were discovered from species of Penicillium for the first time. Compound 1 showed cytotoxicity toward MDA-MB-468 cells with an IC50 value of 38.9 M. Compounds 2 and 11 exhibited inhibition against α-glucosidase with IC50 values of 910 and 525 M, respectively, being more active than the positive control acarbose (1.33 mM).

In vivo continuous evolution of metabolic pathways for chemical production.

Microorganisms have long been used as chemical plant to convert simple substrates into complex molecules. Various metabolic pathways have been optimised over the past few decades, but the progresses were limited due to our finite knowledge on metabolism. Evolution is a knowledge-free genetic randomisation approach, employed to improve the chemical production in microbial cell factories. However, evolution of large, complex pathway was a great challenge. The invention of continuous culturing systems and in vivo genetic diversification technologies have changed the way how laboratory evolution is conducted, render optimisation of large, complex pathway possible. In vivo genetic diversification, phenotypic selection, and continuous cultivation are the key elements in in vivo continuous evolution, where any human intervention in the process is prohibited. This approach is crucial in highly efficient evolution strategy of metabolic pathway evolution.

Costunolide Inhibits the Growth of OAW42-A Multidrug-Resistant Human Ovarian Cancer Cells by Activating Apoptotic and Autophagic Pathways, Production of Reactive Oxygen Species (ROS), Cleaved Caspase-3 and Cleaved Caspase-9.

BACKGROUND Worldwide, ovarian cancer has a high mortality rate due to the difficulty in diagnosing early-stage disease and resistance to chemotherapy agents. Costunolide is a plant-derived sesquiterpene lactone with anti-oxidant properties. This study aimed to investigate the effects of costunolide on cell growth, apoptosis, autophagy, the production of reactive oxygen species (ROS), cleaved caspase-3, and cleaved caspase-9 on the multidrug-resistant ovarian cancer cell line, OAW42-A. MATERIAL AND METHODS The MTT assay determined the proliferation rate of OAW42-A multidrug-resistant ovarian cancer cells and the apoptosis rate was determined using propidium iodide (PI) staining. Autophagy was detected by measuring the expression of LC3 II. Fluorescence flow cytometry was used to measure the levels of reactive oxygen species (ROS) and the mitochondrial membrane potential. Protein expression of LC3 II, beclin 1, cleaved caspase-3, and cleaved caspase-9 were measured by Western blot. RESULTS Costunolide treatment inhibited the growth of OAW42-A cells with an IC50 of 25 µM, resulted in apoptotic cell death, increased the expression of Bax, and decreased the expression of Bcl-2. Confocal electron microscopy showed that costunolide induced autophagy in the OAW42-A cells. Western blot showed that costunolide treatment of OAW42-A cells increased the expression of the LC3 II, beclin 1, cleaved caspase-3, and cleaved caspase-9. Costunolide treatment significantly increased the levels of ROS and reduced the OAW42-A cell mitochondrial membrane potential. CONCLUSIONS Costunolide inhibited growth, apoptosis, ROS generation, and was associated with loss of mitochondrial membrane potential of OAW42-A multidrug-resistant ovarian cancer cells.

Controllable Modular Growth of Hierarchical MOF-on-MOF Architectures.

Fabrication of hybrid MOF-on-MOF heteroarchitectures can create novel and multifunctional platforms to achieve desired properties. However, only MOFs with similar crystallographic parameters can be hybridized by the classical epitaxial growth method (EGM), which largely suppressed its applications. A general strategy, called internal extended growth method (IEGM), is demonstrated for the feasible assembly of MOFs with distinct crystallographic parameters in an MOF matrix. Various MOFs with diverse functions could be introduced in a modular MOF matrix to form 3D core-satellite pluralistic hybrid system. The number of different MOF crystals interspersed could be varied on demand. More importantly, the different MOF crystals distributed in individual domains could be used to further incorporate functional units or enhance target functions.

Pterin-sulfa conjugates as dihydropteroate synthase inhibitors and antibacterial agents.

The sulfonamide class of antibiotics has been in continuous use for over 70years. They are thought to act by directly inhibiting dihydropteroate synthase (DHPS), and also acting as prodrugs that sequester pterin pools by forming dead end pterin-sulfonamide conjugates. In this study, eight pterin-sulfonamide conjugates were synthesized using a novel synthetic strategy and their biochemical and microbiological properties were investigated. The conjugates were shown to competitively inhibit DHPS, and inhibition was enhanced by the presence of pyrophosphate that is crucial to catalysis and is known to promote an ordering of the DHPS active site. The co-crystal structure of Yersinia pestis DHPS bound to one of the more potent conjugates revealed a mode of binding that is similar to that of the enzymatic product analog pteroic acid. The antimicrobial activities of the pterin-sulfonamide conjugates were measured against Escherichia coli in the presence and absence of folate precursors and dependent metabolites. These results show that the conjugates have appreciable antibacterial activity and act by an on target, anti-folate pathway mechanism rather than as simple dead end products.