Robotic Guidance Does Not Improve Component Position or Short-Term Outcome in Medial Unicompartmental Knee Arthroplasty

We performed a retrospective review in a matched group of patients on the use of robotic-assisted UKA implantation versus UKA performed using standard operative techniques to assess differences between procedures. While both techniques resulted in reproducible and excellent outcomes with low complication rates, the results demonstrate little to no clinical or radiographic difference in outcomes between cohorts. Average operative time differed significantly with, and average of 20 minutes greater in, the robotic-assisted UKA group (P = 0.010). Our minimal clinical and radiographic differences lend to the argument that it is difficult to justify the routine use of expensive robotic techniques for standard medial UKA surgery, especially in a well-trained, high-volume surgeon. Further surgical, clinical and economical study of this technology is necessary.     

Top-Down and Bottom-Up Proteomics Methods to Study RNA Virus Biology

RNA viruses cause a wide range of human diseases that are associated with high mortality and morbidity. In the past decades, the rise of genetic-based screening methods and high-throughput sequencing approaches allowed the uncovering of unique and elusive aspects of RNA virus replication and pathogenesis at an unprecedented scale. However, viruses often hijack critical host functions or trigger pathological dysfunctions, perturbing cellular proteostasis, macromolecular complex organization or stoichiometry, and post-translational modifications. Such effects require the monitoring of proteins and proteoforms both on a global scale and at the structural level. Mass spectrometry (MS) has recently emerged as an important component of the RNA virus biology toolbox, with its potential to shed light on critical aspects of virus–host perturbations and streamline the identification of antiviral targets. Moreover, multiple novel MS tools are available to study the structure of large protein complexes, providing detailed information on the exact stoichiometry of cellular and viral protein complexes and critical mechanistic insights into their functions. Here, we review top-down and bottom-up mass spectrometry-based approaches in RNA virus biology with a special focus on the most recent developments in characterizing host responses, and their translational implications to identify novel tractable antiviral targets.     

IFITM3 Interacts with the HBV/HDV Receptor NTCP and Modulates Virus Entry and Infection

The Na⁺/taurocholate co-transporting polypeptide (NTCP, gene symbol SLC10A1) is both a physiological bile acid transporter and the high-affinity hepatic receptor for the hepatitis B and D viruses (HBV/HDV). Virus entry via endocytosis of the virus/NTCP complex involves co-factors, but this process is not fully understood. As part of the innate immunity, interferon-induced transmembrane proteins (IFITM) 1–3 have been characterized as virus entry-restricting factors for many viruses. The present study identified IFITM3 as a novel protein–protein interaction (PPI) partner of NTCP based on membrane yeast-two hybrid and co-immunoprecipitation experiments. Surprisingly, IFITM3 knockdown significantly reduced in vitro HBV infection rates of NTCP-expressing HuH7 cells and primary human hepatocytes (PHHs). In addition, HuH7-NTCP cells showed significantly lower HDV infection rates, whereas infection with influenza A virus was increased. HBV-derived myr-preS1 peptide binding to HuH7-NTCP cells was intact even under IFITM3 knockdown, suggesting that IFITM3-mediated HBV/HDV infection enhancement occurs in a step subsequent to the viral attachment to NTCP. In conclusion, IFITM3 was identified as a novel NTCP co-factor that significantly affects in vitro infection with HBV and HDV in NTCP-expressing hepatoma cells and PHHs. While there is clear evidence for a direct PPI between IFITM3 and NTCP, the specific mechanism by which this PPI facilitates the infection process remains to be identified in future studies.     

Surface phenotypic changes of spleen cells on acquisition of encephalitogenicity

The relationship between surface marker expression and encephalitogenicity of spleen cells was studied in Lewis rats. Donors were sensitized with either BP/CFA or BP/IFA, or given BP-cultured naive spleen cells. The adoptive transfer of EAE was successfully achieved in every case after culture with BP, although only spleen cells from BP/CFA-sensitized rats proliferated significantly in response to BP. The observed encephalitogenicities were BP/CFA-sensitized cells greater than BP/IFA-sensitized cells much greater than cells from recipients of BP-cultured naive cells in descending order. In BP/CFA-sensitized cells, the expression of both W3/25 and OX-3 antigens on T cells increased markedly after culture with BP, but the expression of neither OX-19 nor OX-8 antigen increased significantly. Cells from neither BP/IFA-sensitized rats nor recipients of BP-cultured naive cells showed a significant change in the surface marker expression after culture with BP. Therefore, the generation of T cells coexpressing large amounts of both W3/25 and OX-3 antigens after culture with BP seems to correspond to the acquisition of the strong encephalitogenicity in vivo.