The crude case fatality rate (CFR), because of the calculation method, is the most accurate when the pandemic is over since there is a possibility of the delay between disease onset and outcome. Adjusted crude CFR measures can better explain the pandemic situation by improving the CFR estimation. However, no study has thoroughly investigated the COVID-19 adjusted CFR of the SAARC countries. This study estimated both survival interval and underreporting adjusted CFR of COVID-19 for these countries. Moreover, we assessed the crude CFR between genders and across age groups and observed the CFR changes due to the imposition of fees on COVID-19 tests in Bangladesh. Using the daily records up to October 9, we implemented a statistical method to remove the delay between disease onset and outcome bias, and due to asymptomatic or mild symptomatic cases, reporting rates lower than 50% (95% CI 10%-50%) bias in crude CFR. We found that Afghanistan had the highest CFR, followed by Pakistan, India, Bangladesh, Nepal, Maldives, and Sri Lanka. Our estimated crude CFR varied from 3.708% to 0.290%, survival interval adjusted CFR varied from 3.767% to 0.296% and further underreporting adjusted CFR varied from 1.096% to 0.083%. Furthermore, the crude CFRs for men were significantly higher than that of women in Afghanistan (4.034% vs. 2.992%) and Bangladesh (1.739% vs. 1.337%) whereas the opposite was observed in Maldives (0.284% vs. 0.390%), Nepal (0.006% vs. 0.007%), and Pakistan (2.057% vs. 2.080%).  https://www.selleckchem.com/ferroptosis.html  Besides, older age groups had higher risks of death. Moreover, crude CFR increased from 1.261% to 1.572% after imposing the COVID-19 test fees in Bangladesh. Therefore, the authorities of countries with higher CFR should be looking for strategic counsel from the countries with lower CFR to equip themselves with the necessary knowledge to combat the pandemic. Moreover, caution is needed to report the CFR.New onset refractory status epilepticus (NORSE) was defined by the International League Against Epilepsy as occurring in patients presenting without a prior diagnosis of epilepsy or other neurological disease, with seizures that persist beyond 24 h. There is still a need to develop new treatment strategies for NORSE, particularly for those patients who are least responsive to conventional medical therapies. We present a case of a young female patient without any medical history presenting with status epilepticus, which was refractory not only to anti-seizure medications and anesthetics, but also to conventional immunomodulatory therapies. After nine weeks of electroclinical seizure activity, the patient responded to two doses of tocilizumab.Increased interferon-α (IFN-α) production is a critical component in the pathophysiology of systemic lupus erythematosus (SLE) and other rheumatic autoimmune diseases. Herein, we report the characterization of S95021, a fully human IgG1 anti-IFN-α monoclonal antibody (mAb) as a novel therapeutic candidate for targeted patient populations. S95021 was expressed in CHOZN GS-/- cells, purified by chromatography and characterized by using electrophoresis, size exclusion chromatography and liquid chromatography-mass spectrometry. High purity S95021 was obtained as a monomeric entity comprising different charge variants mainly due to N-glycosylation. Surface plasmon resonance kinetics experiments showed strong association rates with all IFN-α subtypes and estimated KDs below picomolar values. Pan-IFN-α-binding properties were confirmed by immunoprecipitation assays and neutralization capacity with reporter HEK-Blue IFN-α/β cells. S95021 was IFN-α-selective and exhibited superior potency and broader neutralization profile when compared with the benchmark anti-IFN-α mAbs rontalizumab and sifalimumab. STAT-1 phosphorylation and the type I IFN gene signature induced in human peripheral blood mononuclear cells by recombinant IFN-α subtypes or plasmas from selected autoimmune patients were efficiently reduced by S95021 in a dose-dependent manner. Together, our results show that S95021 is a new potent, selective and pan IFN-α-neutralizing mAb. It is currently further evaluated as a valid therapeutic candidate in selected autoimmune diseases in which the IFN-α pro-inflammatory pathway is dysregulated.Lupus erythematosus (LE) is an autoimmune disease that can be divided into two types. The cutaneous lupus erythematosus (CLE), such as discoid LE (DLE), affects only the skin. While the systemic lupus erythematosus (SLE) affects the hematopoietic, renal, and other systems. We previously found that IFI44L methylation could be a biomarker for SLE. Here, we detect the IFI44L methylation by high-resolution melting-quantitative polymerase chain reaction (HRM-qPCR) assay. The positive percentages of SLE, DLE and healthy controls (HC) are 96.00%, 27.45%, 2.00%, if the curve of 25% methylation was used as the threshold of SLE. And we determined the serum IFN-a1 level by enzyme-linked immunosorbent assay (ELISA) in SLE, DLE and HC. The serum concentration of IFN-a1 in patients with SLE was significantly higher than in the DLE (12.63 ± 6.38 pg/mL vs 7.99 ± 2.28 pg/mL, P less then 0.05) and HC (12.63 ± 6.38 pg/mL vs 7.17 ± 1.86 pg/mL, P less then 0.05). But the expression level of IFN-a1 in serum was not significantly different between DLE and HC (7.99 ± 2.28 pg/mL vs 7.17 ± 1.86 pg/mL, P = 0.5365). This suggests that methylation of IFI44L and serum concentration of IFN-a1 may be used as biomarkers to distinguish DLE from SLE.
  Biomarkers are needed to characterize heterogeneity within populations at risk for type 1 diabetes. The ratio of proinsulin to C-peptide (PIC ratio), has been proposed as a biomarker of beta cell dysfunction and is associated with progression to type 1 diabetes. However, relationships between PIC ratios and autoantibody type and number have not been examined. We sought to characterize PIC ratios in multiple islet autoantibody positive, single autoantibody positive and autoantibody negative relatives of individuals with type 1 diabetes.
 
  We measured PIC ratios and autoantibodies with both electrochemiluminescence (ECL) assays (ECL-IAA, ECL-GADA and ECL-IA2A) and radiobinding (RBA) assays (mIAA, GADA, IA2A and ZnT8A) in 98 relatives of individuals with type 1 diabetes followed in the TrialNet Pathway to Prevention Study at the Barbara Davis Center for a mean of 7.4​±​4.1 years. Of these subjects, eight progressed to T1D, 31 were multiple autoantibody (Ab) positive, 37 were single Ab positive and 22 were Ab negative (by RBA).