Two-Year Outcomes of Novel Dual-Mobility Implant in Primary Total Hip Arthroplasty.

Introduction: Dual-mobility (DM) implants for total hip arthroplasty (THA) have gained popularity due to their potential to reduce hip instability and dislocation events that may lead to revision surgery. These implants consist of a femoral head articulated within a polyethylene liner, which articulates within an outer acetabular shell, creating a dual-bearing surface. Our study aimed to report our observations on the survivorship of a novel DM implant for primary total hip arthroplasty at two years.

Indications, Clinical Outcomes, and Re-Revisions Following Revision Total Hip Arthroplasty - Does Age Matter?

Background: Younger age is associated with increased revision incidence following primary total hip arthroplasty, though the association between age and repeat revision following revision total hip arthroplasty (rTHA) has not been described. This study aimed to describe the incidences and indications for subsequent revision (re-revision) following rTHA based on age.

Methods: Patients undergoing aseptic rTHA from 2011 to 2021 with minimum 1-year follow-up were retrospectively reviewed.

Proviral location affects cognate peptide-induced virus production and immune recognition of HIV-1-infected T cell clones.

BACKGROUNDHIV-1-infected CD4+ T cells contribute to latent reservoir persistence by proliferating while avoiding immune recognition. Integration features of intact proviruses in elite controllers (ECs) and people on long-term therapy suggest that proviruses in specific chromosomal locations can evade immune surveillance. However, direct evidence of this mechanism is missing.

PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates.

We have uncovered a role for the promyelocytic leukemia (PML) gene and novel PML-like DEDDh exonucleases in the maintenance of genome stability through the restriction of LINE-1 (L1) retrotransposition in jawed vertebrates. Although the mammalian PML protein forms nuclear bodies, we found that the spotted gar PML ortholog and related proteins in fish function as cytoplasmic DEDDh exonucleases. In contrast, PML proteins from amniote species localized both to the cytoplasm and formed nuclear bodies.

PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial.

Chimeric antigen receptor (CAR) T cells have demonstrated promising efficacy, particularly in hematologic malignancies. One challenge regarding CAR T cells in solid tumors is the immunosuppressive tumor microenvironment (TME), characterized by high levels of multiple inhibitory factors, including transforming growth factor (TGF)-β. We report results from an in-human phase 1 trial of castration-resistant, prostate cancer-directed CAR T cells armored with a dominant-negative TGF-β receptor (NCT03089203).

Antigen-driven clonal selection shapes the persistence of HIV-1-infected CD4+ T cells in vivo.

Clonal expansion of infected CD4+ T cells is a major mechanism of HIV-1 persistence and a barrier to achieving a cure. Potential causes are homeostatic proliferation, effects of HIV-1 integration, and interaction with antigens. Here, we show that it is possible to link antigen responsiveness, the full proviral sequence, the integration site, and the T cell receptor β-chain (TCRβ) sequence to examine the role of recurrent antigenic exposure in maintaining the HIV-1 reservoir.

A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells.

Nine dogs with hemophilia A were treated with adeno-associated viral (AAV) gene therapy and followed for up to 10 years. Administration of AAV8 or AAV9 vectors expressing canine factor VIII (AAV-cFVIII) corrected the FVIII deficiency to 1.9-11.

Lentiviral gene therapy for X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disorder of phagocytic cells. We report the initial results of nine severely affected X-linked CGD (X-CGD) patients who received ex vivo autologous CD34 hematopoietic stem and progenitor cell-based lentiviral gene therapy following myeloablative conditioning in first-in-human studies (trial registry nos. NCT02234934 and NCT01855685).

The distal cytoplasmic tail of the influenza A M2 protein dynamically extends from the membrane.

The influenza A M2 protein is a multifunctional membrane-associated homotetramer that orchestrates several essential events in the viral infection cycle. The monomeric subunits of the M2 homotetramer consist of an N-terminal ectodomain, a transmembrane domain, and a C-terminal cytoplasmic domain. The transmembrane domain forms a four-helix proton channel that promotes uncoating of virions upon host cell entry.