Dual Mobility Trapeziometacarpal Joint Arthroplasty: A Survey on Variations in Surgical Techniques and Patient Management.

Dual mobility total joint arthroplasty is gaining popularity for trapeziometacarpal joint (TMCJ) arthritis, with evolving indications, surgical technique and rehabilitation. The aim of this study was to obtain detailed insight into the variations in indications, surgical technique and rehabilitation for TMCJ arthroplasty with dual mobility implants, across a large international cohort of surgeons. The secondary aim was to analyse if there were differences in TMCJ arthroplasty between highly and less experienced surgeons.

CYP108N14: A Monoterpene Monooxygenase from Rhodococcus globerulus.

Rhodococcus globerulus (R. globerulus) was isolated from the soil beneath a Eucalypt tree. Metabolic growth studies revealed that R.

Synthesis of substituted norcaranes for use as probes of enzyme mechanisms.

Norcarane is a mechanistic probe of monooxygenase enzymes that is able to detect the presence of cationic or radical intermediates. The addition of substituents around the bicycloheptane ring of the norcarane scaffold can assist in improving enzyme binding affinity and thus improve the regioselectivity of oxidation. Here we prepare in three-step, diastereoselective syntheses, ten norcaranes monosubstituted α to the cyclopropane as advanced probes.

Fixed-Bearing Unicompartmental Knee Arthroplasty of the Lateral Compartment: A Series of 246 Cases.

Background: Isolated osteoarthritis of the lateral compartment of the knee is less common than that of the medial compartment, resulting in significantly fewer lateral unicompartmental knee arthroplasties (UKAs) being performed. This study aimed to evaluate results of a fixed-bearing UKA for the treatment of lateral compartment osteoarthritis of the knee.

Methods: A prospectively collected cohort of 255 patients undergoing fixed-bearing UKA of the lateral compartment using the Triathlon PKR (Stryker, Warsaw, IND) implant with a minimum 2-year follow-up was reviewed.

Characterization of the cholesterol biosynthetic pathway in Dioscorea transversa.

Cholesterol is the precursor of bioactive plant metabolites such as steroidal saponins. An Australian plant, Dioscorea transversa, produces only two steroidal saponins: 1β-hydroxyprotoneogracillin and protoneogracillin. Here, we used D.

Cymredoxin, a [2Fe-2S] ferredoxin, supports catalytic activity of the p-cymene oxidising P450 enzyme CYP108N12.

Rhodococcus globerulus is a metabolically active organism that has been shown to utilise eucalypt oil as its sole source of carbon and energy. This oil includes 1,8-cineole, p-cymene and limonene. Two identified and characterised cytochromes P450 (P450s) from this organism initiate the biodegradation of the monoterpenes 1,8-cineole (CYP176A1) and p-cymene (CYP108N12).

CYP108N12 initiates p-cymene biodegradation in Rhodococcus globerulus.

Rhodococcus globerulus (R. globerulus) isolated from soil beneath Eucalyptus sp. was found to live on the monoterpenes 1,8-cineole, p-cymene and (R)- and (S)-limonene as sole sources of carbon and energy.

RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency.

RNA editing by the adenosine deaminase ADAR1 prevents innate immune responses to endogenous RNAs. In ADAR1-deficient cells, unedited self RNAs form base-paired structures that resemble viral RNAs and inadvertently activate the cytosolic RIG-I-like receptor (RLR) MDA5, leading to an antiviral type I interferon (IFN) response. Mutations in ADAR1 cause Aicardi-Goutières Syndrome (AGS), an autoinflammatory syndrome characterized by chronic type I IFN production.

Focal articular surface replacement as primary treatment for focal chondral defects of the femoral condyles: A series of 157 cases.

Background: Focal chondral defects (FCDs) of the femoral condyle are common. Treatment has heretofore primarily consisted of non-surgical and biological treatments. Focal articular surface replacement (FASR) is an emerging technique utilizing small implants to essentially fill the FCD.

Does capsular distension and a short period of countertraction improve outcome following manipulation under anesthesia for the treatment of primary adhesive capsulitis of the glenohumeral joint?

Background: Despite the fact that primary adhesive capsulitis of the glenohumeral joint is often considered a self-limiting condition, not all patients make a full recovery. Manipulation under anesthesia (MUA) is performed to forcibly rupture the contracted capsule in a controlled manner. However, the technique, timing, and use of additional injections are often debated.

CD200R1L is a functional evolutionary conserved activating receptor in human neutrophils.

Inhibitory and activating immune receptors play a key role in modulating the amplitude and duration of immune responses during infection and in maintaining immune balance in homeostatic conditions. The CD200 Receptor (CD200R) gene family in humans encodes one inhibitory receptor, CD200R1, and one putative activating member, CD200R1 Like (CD200R1L). It is demonstrated that CD200R1L is endogenously expressed by human neutrophils and activates cellular functions such as reactive oxygen species (ROS) production via Syk, PI3Kβ, PI3Kδ, and Rac GTPase signaling.

The three-dimensional shape symmetry of the lunate and its implications.

We studied the three-dimensional (3-D) shape variations and symmetry of the lunate to evaluate whether a contralateral shape-based approach to design patient-specific implants for treatment of Kienböck's disease is accurate. A 3-D statistical shape model of the lunate was built using the computed tomography scans of 54 lunate pairs and shape symmetry was evaluated based on an intraclass correlation analysis. The lunate shape was not bilaterally symmetrical in (1) the angle scaphoid surface - radius-ulna surface, (2) the dorsal side and the length of the side adjacent to the triquetrum, (3) the orientation of the volar surface, (4) the width of the side adjacent to the scaphoid, (5) the skewness in the coronal plane and (6) the curvature of bone articulating with the hamate and capitate.

Focal articular surface replacement of knee lesions after failed cartilage repair using focal metallic implants: A series of 132 cases with 4-year follow-up.

Background: Focal articular lesions of the knee can be treated using several different techniques with generally good results, but failures are difficult to manage. Focal articular surface replacement (FASR) using metal implants could be a promising technique that allows defect geometry matching, congruency restoration and defect propagation prevention.

Methods: 132 patients were included who underwent FASR between January 2009 and December 2013.

Self RNA Sensing by RIG-I-like Receptors in Viral Infection and Sterile Inflammation.

The innate immune system uses pattern recognition receptors to survey the intracellular and extracellular environment for signs of infection. Viral infection is detected through the presence of viral nucleic acids in infected cells. Pattern recognition receptor activation by viral nucleic acids induces the expression and secretion of type I IFNs (IFN-Is), important mediators of antiviral immunity.

Structural insights into the role of the acid-alcohol pair of residues required for dioxygen activation in cytochrome P450 enzymes.

The cytochrome P450 heme monooxygenases commonly use an acid-alcohol pair of residues, within the I-helix, to activate iron-bound dioxygen. This work aims to clarify conflicting reports on the importance of the alcohol functionality in this process. Mutants of the P450, CYP199A4 (CYP199A4 and CYP199A4), were prepared, characterised and their crystal structures were solved.

Preoperative embolization in surgical treatment of long bone metastasis: a systematic literature review.

Surgery of long bone metastases is associated with a significant risk of perioperative blood loss, which may necessitate blood transfusion.Successful embolization (> 70% obliteration of vascularity) can be achieved in 36-75% of cases.The reported rate of embolization-related complications is 0-9%.

Biophysical Techniques for Distinguishing Ligand Binding Modes in Cytochrome P450 Monooxygenases.

The cytochrome P450 superfamily of heme monooxygenases catalyzes important chemical reactions across nature. The changes in the optical spectra of these enzymes, induced by the addition of substrates or inhibitors, are critical for assessing how these molecules bind to the P450, enhancing or inhibiting the catalytic cycle. Here we use the bacterial CYP199A4 enzyme (Uniprot entry Q2IUO2), from HaA2, and a range of substituted benzoic acids to investigate different binding modes.

Complete regeneration of large bone defects in rats with commercially available fibrin loaded with BMP-2.

This study aimed at investigating in vitro and in vivo the efficiency of commercially available fibrin as a carrier for controlled and sustained bone morphogenetic protein-2 (BMP-2) release to induce bone formation and reduce the side effects of its use. In vitro release and activity of low-dose recombinant human BMP-2 (rhBMP-2) (37.5 µg/mL) embedded in commercially available fibrin were evaluated and, subsequently, critical-size femur defects in rats were grafted to study bone regeneration and vascularisation by micro-computed tomography (µCT) and histology.

Exploring the substrate specificity of Cytochrome P450.

Cytochromes P450 are enzymes that catalyse the oxidation of a wide variety of compounds that range from small volatile compounds, such as monoterpenes to larger compounds like steroids. These enzymes can be modified to selectively oxidise substrates of interest, thereby making them attractive for applications in the biotechnology industry. In this study, we screened a small library of terpenes and terpenoid compounds against P450 and two P450 mutants, N242A and N242T, that have previously been shown to affect selectivity.

The cubane paradigm in bioactive molecule discovery: further scope, limitations and the cyclooctatetraene complement.

The cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne).

Can Patrolling Liver-Resident T Cells Control Human Malaria Parasite Development?

Recently, a population of non-recirculating, tissue-resident memory CD8 T cells has been identified; cells that seems to act as key sentinels for invading microorganisms with enhanced effector functions. In malaria, the liver represents the first site for parasite development before a definite infection is established in circulating red blood cells. Here, we discuss the evidence obtained from animal models on several diseases and hypothesize that liver-resident memory CD8 T cells (hepatic T) play a critical role in providing protective liver-stage immunity against Plasmodium malaria parasites.

Significance of Protein-Substrate Hydrogen Bonding for the Selectivity of P450-Catalysed Oxidations.

P450 and P450 are bacterial cytochromes P450 that specifically hydroxylate bicyclic monoterpenes. Protein-substrate H bonding has been previously proposed as crucial in the selectivity of P450 oxidations, but not as essential for P450 . To examine the difference in importance of H bonds in these two model P450s, the P450-catalysed oxidation products from thiocamphor were compared.

Selective hydroxylation of 1,8- and 1,4-cineole using bacterial P450 variants.

This study has evaluated the use of the P450 metalloenzymes CYP176A1, CYP101A1 and CYP102A1, together with engineered protein variants of CYP101A1 and CYP102A1, to alter the regioselectivity of 1,8- and 1,4-cineole hydroxylation. CYP176A1 was less selective for 1,4-cineole oxidation when compared to its preferred substrate, 1,8-cineole. The CYP102A1 variants significantly improved the activity over the WT enzyme for oxidation of 1,4- and 1,8-cineole.