Assay Development and Measurement of Autoantibody-Mediated Complement Activity in Myasthenia Gravis

Autoantibodies against the acetylcholine receptor (AChR) play a critical role in myasthenia gravis, where autoantibody-mediated complement activation has been implicated in neuromuscular junction damage. However, the exact pathogenic role of the autoantibodies in complement activation remains unclear. We developed a cell-based assay that measures AChR autoantibody–mediated complement membrane attack complex (MAC) formation. A modified HEK293T cell line using CRISPR/Cas9 genome editing to disrupt expression of the complement regulator genes (CD46, CD55, and CD59)—was used to measure AChR autoantibody–mediated membrane attack complex (MAC) formation through flow cytometry. We observed a modest correlation between autoantibody-mediated complement mediated activity and disease burden suggesting heterogeneity in autoantibody-mediated activation of complement system.&nbsp

The Expressive Energy of Arabic Through Metaphors: Linguistic and Stylistic

DOI: 10.7176/JLLL/62-06 Publication date: November 30th 2019 The importance and justification of the research The first objective of this study is to analyze the nature of linguistic thinking among the Arabs, which helped them to form a nation of intellectual and civilization formation through a culture of its Arabic campaign to the world. As long as the Persians from the circulation of knowledge, and removed the languages of the peoples of the State of the Caliphate, and there is no evidence that the linguists and philosophers Muslim learned, and mastered, and created them. The second goal was to stand at the major rules on which Arab scholars based, in the Middle Ages "from the second to the sixth century AH" These rules and foundations are suitable for non-language in terms of curriculum, especially in their study of the nature of language, and distinguish language from speech, through criteria They developed it, then developed it until it became valid for generalization, assay and conclusion. In the third end, we sought to follow the efforts of linguists, grammarians, and rhetorists to extract a comprehensive basis for the study of "semantics", which compelled them to use science from outside the language "logic" and "natural" to enhance their ability to extrapolate and analyze from the "reality" of the text, and even within it I found out the possibility of generalization ... As for the standing on "truth and metaphor" was the main purpose of the research, and therefore we stopped at the explanations of linguists and rhetoric and their analysis of verses from the wise Quran, and then reviewed their ability to measure between the "text" of the Quran and the words of the Arab poetry and prose, and we entrusted the research towards the methodology of the big and IbnQutaiba and Jurjani imams of Curriculum, language and statement who studied language at the "singular" level and at the "syntax" level. We did not fail to distinguish between the metaphors: stylistic and linguistic, and come to the characteristics of each of them, that - if separated - constitute the unity of Arab rhetorical thinking

Gut Microbiome Dysbiosis in Antibiotic-Treated COVID-19 Patients is Associated with Microbial Translocation and Bacteremia

Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19

Improving the Corrosion Resistance of NiNb-Based Bulk Metallic Glass through the Hot Compression

This paper aims to study and evaluate the corrosion resistance of Ni55Nb45 and Ni55Nb35Co5Zr5 bulk metallic glasses (BMGs) in an environment similar to proton exchange membrane fuel cells. Moreover, the hot compression process was carried out to find the effects of a thermomechanical treatment on the corrosion resistance. The X-ray diffraction (XRD) test indicated that the hot compression process led to formation of crystalline species in both samples; however, it was more pronounced in the Ni55Nb35Co5Zr5 alloy. It is suggested that the minor addition of Zr and Co facilitated the crystallization in the material. The polarization test unveiled that the hot compression deteriorated the corrosion resistance of the Ni55Nb45 alloy through the introduction of anomalous chemical interfaces. On the other hand, the hot deformation affected the Ni55Nb35Co5Zr5 alloy in a positive way, so that the corrosion behavior improved compared with its fully glassy state. It is suggested that the hot deformation induces some NiNb crystalline constituencies in the microstructure of Ni55Nb35Co5Zr5 BMG, leading to the enrichment of glassy matrix from Zr/Co constituencies and the enhancement of corrosion resistance

Remission of severe myasthenia gravis after autologous stem cell transplantation

Abstract Objective Myasthenia gravis (MG) is an autoantibody‐mediated neuromuscular junction disorder involving the acetylcholine receptors on the motor endplate. The safety and response to high‐dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT) were assessed in a patient with severe refractory MG. Methods As part of a pilot study of HDIT/HCT for patients with treatment‐resistant autoimmune neurological disorders, a patient with severe refractory MG underwent treatment. After mobilization of hematopoietic stem cells with rituximab, prednisone, and G‐CSF, the patient had HDIT consisting of carmustine, etoposide, cytarabine, melphalan, and rabbit antithymocyte globulin, followed by autologous HCT. The effect of treatment on the autoantibody to the acetylcholine receptor (AChR) was assessed. Results The patient had been diagnosed with AChR antibody‐positive MG 14 years before HDIT/HCT and had failed thymectomy, therapeutic plasma exchange, and multiple immunomodulatory agents. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was IVb before HDIT/HCT. She tolerated HDIT/HCT well and started to improve clinically within days of treatment. At both 1 and 2 years after HDIT/HCT, patients remained symptom‐free. After HDIT/HCT, AChR‐binding autoantibodies persisted, and the relative frequency of immune cell subtypes shifted. Interpretation HDIT/HCT induced a complete response of disease activity in a patient with severe refractory MG. This response may suggest that a cell‐mediated etiology may be a significant contributing factor in refractory MG cases. A phase 2 clinical trial is warranted to establish if HDIT/HCT can be an effective therapy for severe refractory MG and to gain a further understanding of disease pathogenesis

Sex differences in immune responses that underlie COVID-19 disease outcomes

There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women1,2,3,4,5. However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients’ age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19