Site-Specific Glycosylation Analysis of Murine and Human Fcγ Receptors Reveals High Heterogeneity at Conserved N-Glycosylation Site.

Fc γ-receptors (FcγRs) on leukocytes bind immunoglobulin G (IgG) immune complexes to mediate effector functions. Dysregulation of FcγR-mediated processes contributes to multiple inflammatory diseases, including rheumatoid arthritis, lupus, and immune thrombocytopenia. Critically, immunoregulatory N-glycan modifications on both FcγRs and IgGs alter FcγR-IgG binding affinity. Rapid methods for the characterization of N-glycans across multiple Fcγ receptors are needed to propel investigations into disease-specific contributions of FcγR N-glycans. Here, we utilize nanoliquid chromatography tandem mass spectrometry (nLC-MS/MS) to characterize FcγR glycosylation and report quantitative and site-specific N-glycan characterization of recombinant human FcγRI, FcγRIIIA V158, and FcγRIIIA F158 from CHO cells and murine FcγRI, FcγRIII, and FcγRIV from NS0 cells. Data are available via ProteomeXchange with identifier PXD043966. Broad glycoform distribution (≥30) was observed at mouse FcγRIV site N159 and human FcγRIIIA site N162, an evolutionarily conserved site. Further, mouse FcγRIII N-glycopeptides spanning all four predicted N-glycosylation sequons were detected. Glycoform relative abundances for hFcγRIIIA V/F158 polymorphic variants are reported, demonstrating the clinical potential of this workflow to measure differences in glycosylation between common human FcγRIIIA allelic variants with disease-associated outcomes. The multi-Fcγ receptor glycoproteomic workflow reported here will empower studies focused on the role of FcγR N-glycosylation in autoimmune diseases.

Twinning and development: a genealogy of depoliticisation.

One of the latest methods being trialled across the development sector to help advance progress towards achievement of the Sustainable Development Goals (SDGs) is 'twinning'. In this equation, twinning is rendered as a broadly replicable methodology for improving development outcomes, with a particular emphasis on building up human resources and technical capacity within governments and national bureaucracies. It is time-bound, target driven and depoliticised. However, the relationship between twinning and development has not always looked this way. Our paper uses a genealogical approach to unpack and illuminate the historical circumstances and politico-economic conditions under which these discourses have previously converged. It documents the gradual historical trajectory of the phenomenon of twinning from an overt political act to a largely apolitical tool of development practitioners. In so doing, it denaturalises the status quo and prompts reflection on alternative pathways, politics and practices of development.

Exploring the Relationship Between Usage and Outcomes of an Internet-Based Intervention for Individuals With Depressive Symptoms: Secondary Analysis of Data From a Randomized Controlled Trial.

BACKGROUND: Internet interventions can easily generate objective data about program usage. Increasingly, more studies explore the relationship between usage and outcomes, but they often report different metrics of use, and the findings are mixed. Thus, current evaluations fail to demonstrate which metrics should be considered and how these metrics are related to clinically meaningful change. OBJECTIVE: This study aimed to explore the relationship between several usage metrics and outcomes of an internet-based intervention for depression. METHODS: This is a secondary analysis of data from a randomized controlled trial that examined the efficacy of an internet-based cognitive behavioral therapy for depression (Space from Depression) in an adult community sample. All participants who enrolled in the intervention, regardless of meeting the inclusion criteria, were included in this study. Space from Depression is a 7-module supported intervention, delivered over a period of 8 weeks. Different usage metrics (ie, time spent, modules and activities completed, and percentage of program completion) were automatically collected by the platform, and composite variables from these (eg, activities per session) were computed. A breakdown of the usage metrics was obtained by weeks. For the analysis, the sample was divided into those who obtained a reliable change (RC)-and those who did not. RESULTS: Data from 216 users who completed pre- and posttreatment outcomes were included in the analyses. A total of 89 participants obtained an RC, and 127 participants did not obtain an RC. Those in the RC group significantly spent more time, had more log-ins, used more tools, viewed a higher percentage of the program, and got more reviews from their supporter compared with those who did not obtain an RC. Differences between groups in usage were observed from the first week in advance across the different metrics, although they vanished over time. In the RC group, the usage was higher during the first 4 weeks, and then a significant decrease was observed. Our results showed that specific levels of platform usage, 7 hours total time spent, 15 sessions, 30 tools used, and 50% of program completion, were associated with RC. CONCLUSIONS: Overall, the results showed that those individuals who obtained an RC after the intervention had higher levels of exposure to the platform. The usage during the first half of the intervention was higher, and differences between groups were observed from the first week. This study also showed specific usage levels associated with outcomes that could be tested in controlled studies to inform the minimal usage to establish adherence. These results will help to better understand how to use internet-based interventions and what optimal level of engagement can most affect outcomes. TRIAL REGISTRATION: ISRCTN Registry ISRCTN03704676; http://www.isrctn.com/ISRCTN03704676. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1471-244X-14-147.

Vascular Inflammation in Mouse Models of Systemic Lupus Erythematosus.

Vascular inflammation mediated by overly activated immune cells is a significant cause of morbidity and mortality in systemic lupus erythematosus (SLE). Several mouse models to study the pathogenesis of SLE are currently in use, many of which have different mechanisms of pathogenesis. The diversity of these models allows interrogation of different aspects of the disease pathogenesis. To better determine the mechanisms by which vascular inflammation occurs in SLE, and to assist future researchers in choosing the most appropriate mouse models to study cardiovascular complications in SLE, we suggest that direct comparisons of vascular inflammation should be conducted among different murine SLE models. We also propose the use of in vitro vascular assays to further investigate vascular inflammation processes prevalent among different murine SLE models.

Ancestral Background Is Underreported in Regenerative Engineering.

Purpose: The ancestral background of human cells may play a role in cells' behavior and response to therapeutic interventions in vitro. We investigate the prevalence of ancestry reporting in current biological research and suggest that increased reporting would be beneficial to the field. Methods: Articles published over a six-month period in ten different journals were reviewed for their use of human primary cells and immortalized cell lines, and were analyzed based on whether or not the ancestral or ethnic information of cell donors was ascertainable. Results: The vast majority of literature published in the journals and timeframe we investigated did not report on the ancestral or ethnic origins of the human cells used. Conclusion: There is currently a substantial lack of reporting on the ancestral background of human cells used for research. We suggest that increased ancestral reporting should be implemented in order to improve the development of precision medicine. Lay Summary: Many diseases affect patients of different ancestral backgrounds in a variety of ways. In this perspective article, we raise the concern that, since many scientists do not consider ancestry when designing their studies, their results may not apply to all patients. We use data to show that very few scientists report on the ancestry of the donors who contribute cells and tissues to their research. We suggest that broader reporting on donor ancestry would improve biomedical research and would help doctors to personalize treatments for their patients.Future work includes further increasing awareness of the importance of including ancestry as a variable in experimental design, as well as promoting increased reporting on ancestry in the research community. Supplementary Information: The online version contains supplementary material available at 10.1007/s40883-021-00237-8.

Modeled vascular microenvironments: immune-endothelial cell interactions in vitro.

The advancement of in vitro techniques enables a better understanding of biological processes and improves drug screening platforms. In vitro studies allow for enhanced observation of cell behavior, control over the mimicked microenvironment, and the ability to use human cells. In particular, advances in vascular microenvironment recapitulation are of interest given vasculature influence in cardiovascular vascular diseases and cancer. These investigate alterations in endothelial cell behavior and immune cell interactions with endothelial cells. Specific immune cells such as monocytes, macrophages, neutrophils, and T cells influence endothelial cell behavior by promoting or inhibiting vasculogenesis through cell-cell interaction or soluble signaling. Results from these studies showcase cell behavior in vascular diseases and in the context of tumor metastasis. In this review, we discuss examples of in vitro studies modeling immune cell-endothelial cell interactions to present methods and recent findings in the field. Schematic showcasing common methods of in vitro experimentation of endothelial-immune cell interactions, including interactions with flow, static culture, or in-direct contact.

Potential Applications of Microfluidics to Acute Kidney Injury Associated with Viral Infection.

The kidneys are susceptible to adverse effects from many diseases, including several that are not tissue-specific. Acute kidney injury is a common complication of systemic diseases such as diabetes, lupus, and certain infections including the novel coronavirus (SARS-CoV-2). Microfluidic devices are an attractive option for disease modeling, offering the opportunity to utilize human cells, control experimental and environmental conditions, and combine with other on-chip devices. For researchers with expertise in microfluidics, this brief perspective highlights potential applications of such devices to studying SARS-CoV-2-induced kidney injury.

Anatomic Relationship Between the Hook of the Hamate and the Distal Transverse Carpal Ligament: Implications for Ultrasound-Guided Carpal Tunnel Release.

OBJECTIVE: During ultrasound-guided carpal tunnel release, osseous landmarks may supplement direct visualization of the distal transverse carpal ligament (dTCL) to ensure a complete release. The purpose of this study was to determine the relationship between the apex of the hook of the hamate (aHH) and the dTCL within the transverse safe zone (TSZ) of the carpal tunnel. DESIGN: Twenty unembalmed cadaveric specimens were dissected to determine the aHH-dTCL distance and the aHH-SPA distance (the distance between the aHH and the superficial palmar arch) at the ulnar and radial limits of the TSZ (the distance between the hook of the hamate or ulnar artery to the median nerve). RESULTS: The aHH-dTCL distance averaged 11-12 mm across the TSZ (maximum, 18.2 mm), whereas the aHH-SPA distance was significantly greater on the radial side of the TSZ compared with the ulnar side (22.6 ± 3.6 mm vs. 14.0 ± 4.0 mm). CONCLUSIONS: The dTCL lies approximately 11-12 mm distal to the aHH across the TSZ, with an upper limit of 18.2 mm. Along with direct sonographic visualization of the dTCL, the aHH can be used with other osseous landmarks to estimate the position of the dTCL during ultrasound-guided carpal tunnel release.

Predictive value of inexpensive digital eye and vision photoscreening: "PPV of ABCD".

PURPOSE: Some consumer digital cameras have short flash to lens distances (dimensions) ideal for photoscreening so we adopted them into an ongoing Alaska state wide vision screening program, the Alaska Blind Child Discovery (ABCD) Project. METHODS: Digital cameras with short flash-lens distance were employed by lay screeners trained by a DVD movie. Confirmatory eye examinations by AAPOS (American Association for Pediatric Ophthalmology and Strabismus) criteria were sought from eye doctors. RESULTS: 2900 children were screened in 62 clinics by 14 screeners. Of the 2900 screenings, 99% were readable with 6% refereed as positive for ocular pathology. The positive predictive value was estimated as greater than 80%. The per-screening image cost was less than $0.10 (10 cents) including cameras. Some screeners interpreted images similar to central reading center. CONCLUSION: Pre-literate community eye and vision photoscreening can be both valid and cost effective.

Prevalence and correlates of hepatitis C virus-associated inflammatory arthritis in a population-based cohort.

OBJECTIVES: The objectives of this study were to determine the prevalence of hepatitis C virus-associated inflammatory arthritis, to describe its clinical and immunologic correlates, and to identify features that are characteristic of arthritis in chronic hepatitis C. METHODS: Participants with chronic hepatitis C infection enrolled in a population-based cohort study in Alaska and who had not received anti-viral treatment for hepatitis C were recruited. In a cross-sectional study, we assessed joint symptoms and signs, performed autoantibody and cytokine testing, and abstracted medical records for features of hepatitis C and arthritis. RESULTS: Of the 117 enrolled participants, 8 (6.8%) had hepatitis C-associated arthritis. The participants with arthritis were younger than those without (median age: 45 vs. 52, p = 0.02). Rheumatoid factor was commonly present among patients with hepatitis C-associated arthritis. The only studied autoantibody found more commonly in patients with HCV arthritis than those without arthritis was anti-nuclear antibody (63% vs. 23%, p = 0.026). The only joint symptom significantly more common in hepatitis C arthritis was self-reported joint swelling (75% vs. 26%, p = 0.007). Features of fibromyalgia were more common and functional status was worse in those with arthritis than those without. No cytokines differed in patients with and without arthritis. There were no associations of arthritis or autoantibodies with liver-related outcomes. CONCLUSIONS: In this study of a cohort of individuals with chronic HCV infection, HCV-associated arthritis was present in less than 10%. Few serologic features distinguished participants with or without arthritis, but self-reported joint swelling was more common in those with arthritis.