Impact of COVID-19 infection among indian sickle cell disease patients.

Background: Sickle cell disease (SCD) is one of the most common hemoglobinopathy disorders and is widely prevalent in India, especially in the tribal population. SCD patients are prone to develop recurrent respiratory infections and related complications owing to the microvascular occlusion and impaired immunological response. Objectives: We aimed to determine the prevalence and impact of COVID-19 in SCD patients from India. Methodology: We conducted a cross-sectional study in Chandrapur district of Maharashtra, India, between August and October 2021. After taking informed consent, details of 300 SCD patients' demographic data, history of COVID-19 testing, infection, symptoms related to COVID-19 in the past 1 year, hospitalization, complications, mortality, COVID-19 vaccination, and side effects were recorded. Results: We found that 93 (31%) of SCD patients had influenza-like symptoms during the COVID-19 pandemic with symptoms of fever (81.72%), cough (35.48%), sore throat (18.27%), headache (15.05%), and breathlessness (7.52%). A total of 13 (4.33%) SCD among 300 SCD were tested as COVID positive. Majority of them were mild cases and the 1st dose of COVID-19 vaccine was received by 47 (29.37%) of SCD patients and 10 (6.02%) of the patient had received second dose of vaccine. Conclusion: Low incidence of COVID-19 and milder disease spectrum in our study cohort suggests that there is no increased risk of COVID-19 mortality and morbidity in SCD patients compared to general population. However, the reason for low COVID vaccination in our study could be due to the fear of complications of COVID vaccine.

Role of Oxidative Stress and the Protective Effect of Fermented Papaya Preparation in Sickle Cell Disease.

Fermented papaya preparation (FPP) is the source of antioxidants that may help in reducing the complications associated with oxidative stress and may improve the quality of life in sickle cell disease patients. In this study, we assessed the in vitro effect of FPP on sickled red blood cells (RBCs) using oxidative stress markers and observed that FPP has the potential to reduce the oxidative stress. Scanning electron microscopy (SEM) and eosin 5' malaemide (E5'M) dye test showed that FPP protects red cell morphology against the oxidative stress. Liquid chromatography mass spectrometry (LCMS) analysis of FPP suggests the presence of essential amino acids, vitamin D3, and its derivatives. Fermented papaya preparation can be of benefit either in reducing oxidative stress parameters or in preventing pathophysiological events in the sickle cell disease patients.

Potential involvement of ubiquitin-proteasome system dysfunction associated with oxidative stress in the pathogenesis of sickle cell disease.

The ubiquitin-proteasome system (UPS) is an important intracellular proteolytic pathway responsible for the degradation of proteins and oxidative damage; hence it plays a central role in maintaining homeostasis of red blood cells (RBCs). The present study investigated the levels of polyubiquitination, the function of proteasomes and effect of hydroxycarbamide (HC) therapy in RBCs from sickle cell disease (SCD) patients. Polyubiquitinated proteins were found to be elevated in untreated SCD (UT-SCD) patients compared to those in HC-treated SCD patients (HC-SCD) and controls. Activities of ß1 and ß2 subunits were a little higher in UT-SCD patients, and much higher proteolytic activities were observed in all three subunits (ß1, ß2 and ß5) of RBCs in HC-SCD patients compared to those of UT-SCD patients and controls, although the protein levels of these subunits remained approximately the same. It is notable that, despite HC therapy, some patients showed persistent complications and accumulation of polyubiquitinated proteins. The enhanced proteasomal activity among HC-treated patients might remove the polyubiquitinated protein and could be one of the important mechanisms of therapeutic action. These findings could be useful to understand the pathophysiology of SCD and its clinical heterogeneity and identify a suitable therapeutic target for the better management of these patients.

Small ubiquitin-related modifier ligase activity of Mms21 is required for maintenance of chromosome integrity during the unperturbed mitotic cell division cycle in Saccharomyces cerevisiae.

The SUMO ligase activity of Mms21/Nse2, a conserved member of the Smc5/6 complex, is required for resisting extrinsically induced genotoxic stress. We report that the Mms21 SUMO ligase activity is also required during the unchallenged mitotic cell cycle in Saccharomyces cerevisiae. SUMO ligase-defective cells were slow growing and spontaneously incurred DNA damage. These cells required caffeine-sensitive Mec1 kinase-dependent checkpoint signaling for survival even in the absence of extrinsically induced genotoxic stress. SUMO ligase-defective cells were sensitive to replication stress and displayed synthetic growth defects with DNA damage checkpoint-defective mutants such as mec1, rad9, and rad24. MMS21 SUMO ligase and mediator of replication checkpoint 1 gene (MRC1) were epistatic with respect to hydroxyurea-induced replication stress or methyl methanesulfonate-induced DNA damage sensitivity. Subjecting Mms21 SUMO ligase-deficient cells to transient replication stress resulted in enhancement of cell cycle progression defects such as mitotic delay and accumulation of hyperploid cells. Consistent with the spontaneous activation of the DNA damage checkpoint pathway observed in the Mms21-mediated sumoylation-deficient cells, enhanced frequency of chromosome breakage and loss was detected in these mutant cells. A mutation in the conserved cysteine 221 that is engaged in coordination of the zinc ion in Loop 2 of the Mms21 SPL-RING E3 ligase catalytic domain resulted in strong replication stress sensitivity and also conferred slow growth and Mec1 dependence to unchallenged mitotically dividing cells. Our findings establish Mms21-mediated sumoylation as a determinant of cell cycle progression and maintenance of chromosome integrity during the unperturbed mitotic cell division cycle in budding yeast.

Removal of Ni (II) ions from aqueous solutions by biosorption onto two strains of Yarrowia lipolytica.

The removal of Ni (II) ions from aqueous solutions by two strains of Yarrowia lipolytica (NCIM 3589 and NCIM 3590) under different environmental conditions was studied. Biosorption of Ni (II) was enhanced with an increase in pH, temperature, agitation, contact time and initial concentration of the metal ion. NCIM 3589 and NCIM 3590 at pH 7.5 in the presence of 1000 mg L(-1) Ni (II) at 35 °C exhibited a maximum uptake of 95.33 mg g(-1) and 85.44 mg g(-1), respectively. The experimental data fitted well to the Langmuir as well as the Freundlich isotherms. Dubinin-Radushkevich (D-R) isotherms suggested that a chemical ion-exchange mechanism was involved in the biosorption process. The biosorption process followed the pseudo-second-order kinetic mechanism with liquid film diffusion being the rate limiting step. Fourier transform infra red (FTIR) spectroscopic studies suggested the possible involvement of hydroxyl, caboxyl, carbonyl and amino groups in process of biosorption. Scanning electron microscopy and energy dispersive spectra (SEM-EDS) confirmed biosorption of Ni (II).

Effect of Different Rituximab Doses on B Cell Count, Anti-A/B Antibody Titer, Graft Function, and Infectious Complications in ABO-Incompatible Renal Transplantation: A Prospective Study.

BACKGROUND: ABO-incompatible kidney transplantation (ABOiKT) has been accepted as a viable and cost-effective modality with outcomes comparable to ABO-compatible transplants, but there is a concern regarding higher infectious complications in ABOiKT because of the heightened immunosuppression. The desensitization protocol normally includes antibody removal, B cell depletion by rituximab (RTX), and immunomodulation with intravenous immunoglobulin. Efforts have been made over the years to decrease the dose of RTX in an effort to decrease the infective complications. There is limited literature about the minimum effective dose of RTX, which can cause an effective B cell depletion. This prospective study was designed to correlate the RTX dose with peripheral absolute B cell count, graft function, graft and patient survival, and infective complications. METHODS: This study included 52 adult ABOiKT recipients with anti-A/B antibody titer up to a maximum of 1:512. The participants were divided into 2 groups of 26 each according to the RTX dosage used: Group A received 100 mg/patient, and Group B received 200 mg/patient. RTX was given 14 days prior to transplant after B cell measurement by flow cytometry. The outcomes were compared after 1 year of follow-up. RESULTS: Both the dosages effectively depleted the absolute B cell count. Although patient survivals, graft survival, graft function, acute rejection episodes, and post-transplant hospital stay were similar in both groups, infective complications were significantly higher in group B. CONCLUSION: A low dose (100 mg/patient) of RTX produces effective depletion of B cells while lowering the infective complications in ABOiKT.

Multicenter Evaluation of HemoTypeSC as a Point-of-Care Sickle Cell Disease Rapid Diagnostic Test for Newborns and Adults Across India.

OBJECTIVES: Sickle cell anemia is the commonest genetic disorder in India, and the frequency of the sickle cell gene is very high in the remote tribal areas where facilities are generally limited. Therefore, a rapid and affordable point-of-care test for sickle cell disease is needed. METHODS: The diagnostic accuracy of HemoTypeSC was evaluated against automated high-performance liquid chromatography (HPLC) as the gold standard for its efficacy in a newborn screening program. RESULTS: A total of 1,559 individuals (980 newborns and 579 adults) from four participating centers were analyzed by both methods. HemoTypeSC correctly identified 209 of 211 total hemoglobin (Hb) SS cases, for a 99.1%/99.9% total HbSS sensitivity/specificity. Overall, HemoTypeSC exhibited sensitivity and specificity of 98.1% and 99.1% for all possible phenotypes (HbAA, HbAS, and HbSS) detected. HPLC is relatively expensive and not available in most laboratories in remote tribal areas. CONCLUSIONS: We conclude that the rapid, point-of-care testing device HemoTypeSC test is suitable for population and newborn screening for the HbS phenotype.

Successful Third Kidney Transplant After Desensitization for Combined Human Leucocyte Antigen (HLA) and ABO Incompatibility: A Case Report and Review of Literature.

BACKGROUND In the present era, kidney transplantation across immunological barriers (ABO incompatibility and human leucocyte antigen (HLA) incompatibility) is a successful strategy to provide transplantation to immunologically high-risk patients. The safety and outcome of crossing both ABO and HLA barriers simultaneously in a retransplantation scenario is rarely reported from the developing world. CASE REPORT A 30-year-old female underwent a third living donor kidney transplantation. Her previous 2 transplants being lost to chronic allograft nephropathy. The transplantation was done across a simultaneous blood group as well as HLA incompatibility. The donor was the mother who was blood group B, with the recipient being blood group O. The complement dependent cytotoxicity crossmatch of the pair was negative but the flow cross match for T as well as B lymphocytes was positive. The mean fluorescence intensity value for class I antigens was 6951 and that for class 2 antigens was 7534. The patient underwent a desensitization procedure including rituximab, plasmapheresis and intravenous immunoglobulin pre-transplantation. The pre-transplantation isohemaglutunin titer was <1: 8 and the donor specific antibody against class 1 antigens was <2200 and <770 against class 2 antigens. Induction was done with anti-thymocyte globulin in the dose of 3 mg/kg in 2 divided doses. The patient is maintained on triple immunosuppression with tacrolimus, prednisolone and mycophenolate mofetil. After a follow-up period of 5 months, she maintains a good graft function with serum creatinine of 1.01 mg/dL. CONCLUSIONS With the advances in the desensitizing procedures in the developing world, kidney transplantation across a combined HLA and ABO incompatible barrier can be offered to these highly sensitized patients, even in case of retransplantation.