B cells are important as antigen presenting cells for induction of MHC-restricted arthritis in transgenic mice

Rheumatoid arthritis and its animal model, collagen-induced arthritis, are known as a T and B cell dependent disease. To analyze the role of B cells in arthritis, we generated B cell deficient (microMT) mice carrying HLA-DQ8 as transgene, Abetao.DQ8.micromt mice. HLA-DQ8 transgenic mice (Abetao.DQ8) are susceptible to collagen induced arthritis, an animal model for inflammatory arthritis. Deletion of IgM gene led to the absence of B cells while T cells were comparable to Abetao.DQ8 mice. Arthritis and autoantibodies was completely abrogated in B cell deficient DQ8 mice. T cell response and proinflammatory cytokine production in response to type II collagen and its derived peptides in vitro was significantly decreased despite an increased number of Mac-1 positive cells in DQ8.micromt mice compared to DQ8 mice suggesting B cells could be important for antigen presentation as well. In vitro substitution of B cells from wild type mice restored the response in DQ8.micromt mice. B cells could also present CII-derived peptides to antigen-specific DQ8-restricted hybridomas reinforcing the role of B cells in presentation of antigens to T cells. The data suggest that B cells can be involved in pathogenesis of arthritis by producing autoantibodies and antigen presentation.     

Pupillodynamics and corneal spherical aberrations in a set of Indian cataract patients and its implications for aberrometric customisation of intraocular lenses

Purpose:Assessment of pupil diameter in various light conditions and the corresponding corneal spherical aberrations in a cohort of Indian eyes with bilateral senile cataracts and the possible use of this data in aberrometric customization of intraocular lenses (IOLs).Methods:In this prospective observational study done at a tertiary eye care centre in India, the selected patients were subjected to measurement of their pupil diameters in scotopic, mesopic, and photopic conditions as well as the corresponding corneal spherical aberrations, using the Sirius Topographer (Costruzione Strumenti Oftalmici, Florence, Italy). Shapiro–Wilk test, Independent t-test, ANOVA with Bonferroni correction on post-hoc testing were used for statistical analysis.Results:104 eyes of 52 patients were enrolled for the study. The mean age was 53 ± 11.88 years. The mean scotopic, mesopic, and photopic pupil sizes were 4.37 mm (4.11–4.63 mm), 3.92 mm (3.71 mm–4.15 mm), and 3.37 mm (3.18–3.67 mm), respectively. There was a statistically significant difference (P = <0.001) in the mean corneal spherical aberration measured at the 6 mm zone (0.23 ± 0.02 microns) and at the 4 mm zone (0.06 ± 0.01 microns).Conclusion:The mean corneal spherical aberration corresponding to the average mesopic pupil size of our patient population was substantially lower than that of the scotopic pupil size and also less than the amount corrected by most of the negative aspheric IOLs. This perhaps indicates the need for customising IOLs based on the spherical aberrations of cornea at the zone corresponding to the mesopic pupil diameter for optimal residual total postoperative spherical aberrations.     

Beyond bone biology: Lessons from team science

Today, research in biomedicine often requires the knowledge and technologies in diverse fields. Therefore, there is an increasing need for collaborative team science that crosses traditional disciplines. Here, we discuss our own lessons from both interdisciplinary and transdisciplinary teams, which ultimately ushered us to expand our research realm beyond bone biology.     

Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can cause neurological disease in humans, but little is known about the pathogenesis of SARS-CoV-2 infection in the central nervous system (CNS). Herein, using K18-hACE2 mice, we demonstrate that SARS-CoV-2 neuroinvasion and encephalitis is associated with mortality in these mice. Intranasal infection of K18-hACE2 mice with 10⁵ plaque-forming units of SARS-CoV-2 resulted in 100% mortality by day 6 after infection. The highest virus titers in the lungs were observed on day 3 and declined on days 5 and 6 after infection. By contrast, very high levels of infectious virus were uniformly detected in the brains of all the animals on days 5 and 6. Onset of severe disease in infected mice correlated with peak viral levels in the brain. SARS-CoV-2-infected mice exhibited encephalitis hallmarks characterized by production of cytokines and chemokines, leukocyte infiltration, hemorrhage and neuronal cell death. SARS-CoV-2 was also found to productively infect cells within the nasal turbinate, eye and olfactory bulb, suggesting SARS-CoV-2 entry into the brain by this route after intranasal infection. Our data indicate that direct infection of CNS cells together with the induced inflammatory response in the brain resulted in the severe disease observed in SARS-CoV-2-infected K18-hACE2 mice.     

ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project

The International Peripheral T-Cell Lymphoma Project is a collaborative effort designed to gain better understanding of peripheral T-cell and natural killer (NK)/T-cell lymphomas (PTCLs). A total of 22 institutions in North America, Europe, and Asia submitted clinical and pathologic information on PTCLs diagnosed and treated at their respective centers. Of the 1314 eligible patients, 181 had anaplastic large-cell lymphoma (ALCL; 13.8%) on consensus review: One hundred fifty-nine had systemic ALCL (12.1%) and 22 had primary cutaneous ALCL (1.7%). Patients with anaplastic lymphoma kinase–positive (ALK⁺) ALCL had a superior outcome compared with those with ALK^– ALCL (5-year failure-free survival [FFS], 60% vs 36%; P = .015; 5-year overall survival [OS], 70% vs 49%; P = .016). However, contrary to prior reports, the 5-year FFS (36% vs 20%; P = .012) and OS (49% vs 32%; P = .032) were superior for ALK^– ALCL compared with PTCL, not otherwise specified (PTCL-NOS). Patients with primary cutaneous ALCL had a very favorable 5-year OS (90%), but with a propensity to relapse (5-year FFS, 55%). In summary, ALK^– ALCL should continue to be separated from both ALK⁺ ALCL and PTCL-NOS. Although the prognosis of ALK^– ALCL appears to be better than that for PTCL-NOS, it is still unsatisfactory and better therapies are needed. Primary cutaneous ALCL is associated with an indolent course.     

Pangolin Indexing System: implications in forensic surveillance of large seizures

International Journal of Legal Medicine - Demand for pangolin scales in East Asia has increased dramatically in the past two decades, raising concern to the pangolin survival and bringing them to...