Restricted processing of CD16a/Fc γ receptor IIIa N-glycans from primary human NK cells impacts structure and function

CD16a/Fc γ receptor IIIa is the most abundant antibody Fc receptor expressed on human natural killer (NK) cells and activates a protective cytotoxic response following engagement with antibody clustered on the surface of a pathogen or diseased tissue. Therapeutic monoclonal antibodies (mAbs) with greater Fc-mediated affinity for CD16a show superior therapeutic outcome; however, one significant factor that promotes antibody–CD16a interactions, the asparagine-linked carbohydrates (N-glycans), remains undefined. Here, we purified CD16a from the primary NK cells of three donors and identified a large proportion of hybrid (22%) and oligomannose N-glycans (23%). These proportions indicated restricted N-glycan processing and were unlike those of the recombinant CD16a forms, which have predominantly complex-type N-glycans (82%). Tethering recombinant CD16a to the membrane by including the transmembrane and intracellular domains and via coexpression with the Fc ϵ receptor γ–chain in HEK293F cells was expected to produce N-glycoforms similar to NK cell–derived CD16a but yielded N-glycoforms different from NK cell–derived CD16a and recombinant soluble CD16a. Of note, these differences in CD16a N-glycan composition affected antibody binding: CD16a with oligomannose N-glycans bound IgG1 Fc with 12-fold greater affinity than did CD16a having primarily complex-type and highly branched N-glycans. The changes in binding activity mirrored changes in NMR spectra of the two CD16a glycoforms, indicating that CD16a glycan composition also affects the glycoprotein\u27s structure. These results indicated that CD16a from primary human NK cells is compositionally, and likely also functionally, distinct from commonly used recombinant forms. Furthermore, our study provides critical evidence that cell lineage determines CD16a N-glycan composition and antibody-binding affinity

Use of Foscarnet Therapy for EBV Infection following Control of PTLD with Enhancement of Cellular Immunity in a Lung-Transplant Recipient

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation with an annual incidence rate of 3–5% in lung-transplant recipients. Pathogenesis indicates a strong association with functional over-immunosuppression and EBV infection. Clinical improvement is generally observed with reduction in immunosuppression intensity alone. We present a case of a 24-year-old woman with EBV-associated PTLD following lung transplant where decreasing the immunosuppression improved PTLD but was ineffective against controlling the EBV infection. Foscarnet in combination with immunoglobulins was successfully administered to cause a remission of the EBV infection. This is the second case reported of a persistent EBV infection after reducing immunosuppression levels and evidence of PTLD remission that required foscarnet for EBV infection control

The role of accelerator programmes in supporting the adoption of digital health technologies: A qualitative study of the perspectives of small- and medium-sized enterprises

Objective Evidence-based digital health technologies are increasingly important in delivering care to an ageing population with constrained resources. In the United Kingdom, accelerator programmes (APs) have been developed to support the adoption of digital health technologies within the National Health Service. This study aims to explore the perspectives of stakeholders using APs. Methods Stakeholders representing nine small -and medium-sized enterprises (SMEs) that were engaged with three different APs ( n = 9). Semi-structured interviews were conducted with key informants between April and September 2018. Framework analysis of the data was performed to explore their perspectives on APs. Results Four key themes were generated. Informants reported the need to generate evidence before and during the programme, appreciating different types of evidence and their importance. Informants identified several key factors that were a catalyst for success, including involvement in the programme and access to individuals and organisations that were crucial for support. However, several barriers were identified at the programme and system levels. Finally, informants identified key supporting processes that enhanced the adoption of their innovations. Conclusion SMEs that develop digital health technologies report that, while APs are useful in supporting the adoption of these technologies, some issues remain. These relate to the emphasis on traditional research evidence that remains a challenge for SMEs to generate. Also, several system-level barriers to innovation in healthcare persist. As APs and SMEs continue to create an entrepreneurial ecosystem, there is increased potential for the development of supporting processes and infrastructure to accelerate the efficient and timely adoption of new digital health technologies

An Unusual Presentation of Endocarditis Caused by Staphylococcus warneri

Staphylococcus warneri does not generally cause serious infections in humans. We report a case of endocarditis in a healthy individual with no known past medical history. S. warneri was identified in her blood cultures and echocardiographic evidence confirmed the diagnosis of bacterial endocarditis. There was no apparent cause for her infection, and risk factors such as invasive treatment or medical implant were not present. This rare clinical presentation illustrates the importance of not overlooking low virulence species of Staphylococcus, as they can potentially serve as opportunistic etiological agents for endocarditis, especially among the elderly population

Proximal femoral fracture in a man resulting from modern clipless pedals: a case report

<p>Abstract</p> <p>Introduction</p> <p>The use of clipless pedals amongst recreational cyclists has become increasingly popular in recent years. We describe a hip fracture, that was sustained due to inadequate set up of such pedals. To the best of our knowledge, this has only been described once before, and this was in the non-English language medical literature.</p> <p>Case Report</p> <p>A 38-year-old Caucasian man who was a club cyclist sustained a displaced intracapsular fracture of the hip whilst cycling. As a direct result of the incorrect set-up of his clipless pedals he was unable to release his feet whilst slowing to a halt. This resulted in a loss of balance and subsequent fall with a direct impact onto his left hip. The resulting fracture was managed successfully with early closed reduction and fixation. At six month review he was walking unaided without pain but, as yet, has been unable to return to cycling.</p> <p>Conclusion</p> <p>This case highlights the dangers of clipless pedals even in experienced cyclists, and underlines the importance of proper information for their correct setup to minimise the risk of potentially serious injuries, especially in the region of the hip.</p

Optical and structural properties of CdS​/ZnSe bi-​layer thin films prepared by e-​beam technique

Single- and bi-​layer thin films of Cadmium Sulfide (CdS) and Zinc Selenide (ZnSe) were prepd. on glass and ITO​/Glass substrates by e-​beam technique. Spectral transmittance of bi-​layer thin film showed red shift with prolonged interference effect. The decrease in Urbach tail of bi-​layer thin film signifies the decreased band gap with increased grain size. Single layer CdS film has prominent (002) hexagonal peak where as bi-​layer thin film confirm with (002) hexagonal and (111) cubic peaks of CdS and ZnSe resp. CdS grain size was found to be 14.5, 17.1, and 33.1 nm on glass, ITO​/Glass and ZnSe​/ITO​/Glass substrates resp