Mechanistic Investigation of the Pseudo-Halogen Effect in Enantioselective Aminocatalyzed [6 + 4] and [10 + 6] Cycloadditions: Enabling Unique Favorskii-Like Rearrangements.

A mechanistic investigation into the novel combination of the -halogen effect with enantioselective aminocatalysis unravels the mechanistic intricacies of [6 + 4] and [10 + 6] higher-order cycloadditions and the succeeding new Favorskii-like rearrangements. By introducing the OTf-group into the tropone framework, it can serve both as an activator for the cycloaddition and as a proficient leaving group within the corresponding cycloadduct, thus enabling unprecedented ring-contracting Favorskii-like rearrangements. Integrating the -OTf group creates an electron-deficient 6π-component leveraging the -halogen effect by enhancing the polarization and introducing new strategic interaction points.

Enantioconvergent 6π Electrocyclization Enabled by Photoredox Racemization.

This study presents a novel photoredox-enabled enantioconvergent catalytic strategy used to construct chiral 2-1,3-benzoxazines via an unprecedented oxa-6π electrocyclization utilizing racemic α-substituted glycinates as substrates. The approach leverages a cobalt-based chiral Lewis acid catalyst, which promotes the transformation under thermal or photoredox conditions. While the thermal reaction selectively converts only the ()-configured glycinates into enantioenriched 2-1,3-benzoxazines (up to 96:4 e.

Melanoma patients with immune-related adverse events after immune checkpoint inhibitors are characterized by a distinct immunological phenotype of circulating T cells and M-MDSCs.

Treatment with immune checkpoint inhibitors (ICIs) has improved the prognosis of melanoma patients. However, ICIs can cause an overactivation of the immune system followed by diverse immunological side effects known as immune-related adverse events (irAE). Currently, the toxicity of irAE is limiting the usage of ICIs.

Immunosuppressive capacity of circulating MDSC predicts response to immune checkpoint inhibitors in melanoma patients.

Purpose: Although the treatment of advanced melanoma patients with immune checkpoint inhibitors (ICI) significantly increased the therapeutic efficiency, many patients remain resistant to ICI that could be due to immunosuppression mediated by myeloid-derived suppressor cells (MDSC). These cells are enriched and activated in melanoma patients and could be considered as therapeutic targets. Here we studied dynamic changes in immunosuppressive pattern and activity of circulating MDSC from melanoma patients treated with ICI.

Asymmetric Organocatalyzed Cascade Reactions─Merging the -Halogen and Halogen Effect with Dienamine Catalysis.

The combination of asymmetric organocatalysis with the ()-halogen effect enables the formation of chiral norcarane scaffolds in high yields and selectivities (up to 92% yield, >99% ee, and >95:5 d.r.).

Higher-Order Cycloaddition Reactions for the Construction of Polycyclic Aromatic and Polycyclic Heteroaromatic Compounds.

Cycloadditions are an important class of reactions in materials science for the construction of polycyclic aromatic and polycyclic heteroaromatic compounds. Recently, cycloadditions have been expanded beyond the "classical" group of cycloadditions involving six π-electrons, and it is now possible to control cycloadditions for an extended number of π-electrons by applying organocatalysis. This novel field of cycloadditions-termed higher-order cycloadditions-allows new synthetic methodologies to construct polycyclic carbo- and heteroaromatic compounds in two or three dimensions.

Booster dose of mRNA vaccine augments waning T cell and antibody responses against SARS-CoV-2.

A gradual decay in humoral and cellular immune responses over time upon SAR1S-CoV-2 vaccination may cause a lack of protective immunity. We conducted a longitudinal analysis of antibodies, T cells, and monocytes in 25 participants vaccinated with mRNA or ChAdOx1-S up to 12 weeks after the 3 (booster) dose with mRNA vaccine. We observed a substantial increase in antibodies and CD8 T cells specific for the spike protein of SARS-CoV-2 after vaccination.

HSP90α induces immunosuppressive myeloid cells in melanoma via TLR4 signaling.

Background: Tumor cells modulate host immunity by secreting extracellular vesicles (EV) and soluble factors. Their interactions with myeloid cells lead to the generation of myeloid-derived suppressor cells (MDSC), which inhibit the antitumor function of T and NK cells. We demonstrated previously that EV derived from mouse and human melanoma cells induced immunosuppressive activity via increased expression of programmed cell death ligand 1 (PD-L1) on myeloid cells that was dependent on the heat-shock protein 90α (HSP90α) in EV.

Does tibial design modification improve implant stability for total knee arthroplasty? An experimental cadaver study.

Aims: One of the main causes of tibial revision surgery for total knee arthroplasty is aseptic loosening. Therefore, stable fixation between the tibial component and the cement, and between the tibial component and the bone, is essential. A factor that could influence the implant stability is the implant design, with its different variations.

STAT3 inhibitor Napabucasin abrogates MDSC immunosuppressive capacity and prolongs survival of melanoma-bearing mice.

Background: Myeloid-derived suppressor cells (MDSCs) represent a negative prognostic factor in malignant melanoma. These cells are generated under chronic inflammatory conditions typical of cancer. The transcription factor signal transducer and activator of transcription 3 (STAT3) orchestrates MDSC accumulation and acquisition of immunosuppressive properties.

The primary stability of the femoral component in cemented single and twin peg Oxford unicompartmental knee arthroplasty under adverse conditions.

Aims: The cemented Oxford unicompartmental knee arthroplasty (OUKA) features two variants: single and twin peg OUKA. The purpose of this study was to assess the stability of both variants in a worst-case scenario of bone defects and suboptimal cementation.

Methods: Single and twin pegs were implanted randomly allocated in 12 pairs of human fresh-frozen femora.

Pulsatile Lavage Systems with High Impact Pressure and High Flow Produce Cleaner Cancellous Bone Prior to Cementation in Cemented Arthroplasty.

In cemented joint arthroplasty, state-of-the-art cementing techniques include high-pressure pulsatile saline lavage prior to cementation. Even with its outstanding importance in cementation, there are surprisingly few studies regarding the physical parameters that define pulsatile lavage systems. To investigate the parameters of impact pressure, flow rate, frequency and the cleaning effect in cancellous bone, we established a standardized laboratory model.

Cement debonding behaviors of the various tibial components of the ATTUNE knee system and its predecessors: Is a cement-in-cement revision an alternative?

Background: Aseptic loosening remains one of the most common causes of revision of the tibial component for total knee arthroplasty. A stable bond between implant and cement is essential for appropriate long-term results. The aim of our in vitro study was to investigate the maximum failure load of tibial ATTUNE prosthesis design alternatives compared with a previous design.

Pulsatile Lavage Improves Tibial Cement Penetration and Implant Stability in Medial Unicompartmental Arthroplasty: A Cadaveric Study.

Cemented unicompartmental knee arthroplasty (UKA) shows good survivorship and function. However, implant failure, causing the need for revision, can occur. Aseptic loosening is still among the most common reasons for revision.

A Direct Organocatalytic Enantioselective Route to Functionalized trans-Diels-Alder Products Having the Norcarane Scaffold.

An enantioselective methodology to construct trans-Diels-Alder scaffolds by organocatalysis with excellent selectivity, high yield and up to five contiguous stereocenters is presented. The reaction concept integrates the halogen effect and a novel discovered pseudo-halogen effect to direct an endo-selective, secondary-amine catalyzed Diels-Alder reaction allowing for the subsequent formation of trans-Diels-Alder cycloadducts featuring the norcarene scaffold. The methodology relies on the reaction between an in situ generated trienamine and an α-brominated or α-pseudo-halogenated enone to form a fleeting cis-Diels-Alder intermediate.

Early tibial loosening of the cemented ATTUNE knee arthroplasty - Just a question of design?

Background: Total knee arthroplasty is a very successful standard treatment for severe osteoarthritis. Nevertheless, the literature reports tibial debonding between implant and bone cement as well as radiolucent lines related to the tibial components of different knee systems. Regardless of cementing techniques and the influences during surgery, we examined the design of a newly developed knee system and its predecessors (Attune, Attune S+, P.

Comparison of the Primary Stability of Porous Tantalum and Titanium Acetabular Revision Constructs.

Adequate primary stability of the acetabular revision construct is necessary for long-term implant survival. The difference in primary stability between tantalum and titanium components is unclear. Six composite hemipelvises with an acetabular defect were implanted with a tantalum augment and cup, using cement fixation between cup and augment.

Retrieval Analysis of Modern Knee Tumor Megaendoprosthesis Shows Considerable Volumetric Metal Wear Generated at the Rotating Hinge.

Frequently occurring damage, as well as elevated blood metal ion levels, are reported in relation to a tumor and revision system for total knee arthroplasty (TKA), which applies a rotating hinge coupling with a metal-on-metal (MoM) articulation. As the patient collective for this specific system is small, there is no data on wear generated from the couplings. In this study, wear volume and influencing parameters were investigated at 44 retrieved TKAs with MoM couplings.

En-Bloc Resection of Metastases of the Proximal Femur and Reconstruction by Modular Arthroplasty is Not Only Justified in Patients with a Curative Treatment Option-An Observational Study of a Consecutive Series of 45 Patients.

Background: There is little conformity regarding the surgical treatment of metastasis of the proximal femur, especially in palliative patients with limited life expectancy.

Patients And Methods: En-bloc resection of secondary bone malignancies of the proximal femur and reconstruction by modular arthroplasty was performed in a consecutive series of 45 patients. The mean follow-up period was 16.

Titanium Acetabular Component Deformation under Cyclic Loading.

Acetabular cup deformation may affect liner/cup congruency, clearance and/or osseointegration. It is unclear, whether deformation of the acetabular components occurs during load and to what extent. To evaluate this, revision multi-hole cups were implanted into six cadaver hemipelvises in two scenarios: without acetabular defect (ND); with a large acetabular defect (LD) that was treated with an augment.

Femoral neck prostheses: A systematic analysis of the literature.

Primary total hip arthroplasty (THA) is one of the most successful surgical procedures. Considering the demographic change the use of new ultra-short femoral implants has gained importance especially when treating young patients. Main features are bone conservation, metaphyseal anchoring and thus reducing stress shielding by proximal load transferring.

Femoral Cementation in Knee Arthroplasty-A Comparison of Three Cementing Techniques in a Sawbone Model Using the ATTUNE Knee.

Femoral component loosening is a rare but severe complication in total knee arthroplasty. Former studies have repeatedly demonstrated radiolucent lines behind the ventral and dorsal anchoring shields of the femoral components, which has led us to investigate this matter further. Therefore, three different cementing techniques were tested in a group of nine Sawbone samples each.

Three dimensional gait analysis in patients with symptomatic component mal-rotation after total knee arthroplasty.

Purpose: Purpose of the present cohort study was the determination of lower body function and rotation in patients with symptomatic component mal-rotation after total knee arthroplasty using instrumented 3D gait analysis.

Methods: A consecutive series of 12 patients (61.3 years ± 11.

Comparison of the stability of three fixation techniques between porous metal acetabular components and augments.

Objectives: In order to address acetabular defects, porous metal revision acetabular components and augments have been developed, which require fixation to each other. The fixation technique that results in the smallest relative movement between the components, as well as its influence on the primary stability with the host bone, have not previously been determined.

Methods: A total of 18 composite hemipelvises with a Paprosky IIB defect were implanted using a porous titanium 56 mm multihole acetabular component and 1 cm augment.

Can intraoperative measurement of bone quality help in decision making for cementless unicompartmental knee arthroplasty?

Background: In uncemented total hip arthroplasty (THA), low bone mineral density (BMD) is associated with aseptic loosening. BMD is usually assessed via dual-energy X-ray absorptiometry (DXA) or quantitative computed tomography, which takes time and exposes patients to radiation. Due to its low risk profile, intraoperative measurement of the trabecular stability might be a useful alternative to DXA.