Oro-Respiratory Dysbiosis and Its Modulatory Effect on Lung Mucosal Toxicity during Exposure or Co-Exposure to Carbon Nanotubes and Cigarette Smoke.

The oro-respiratory microbiome is impacted by inhalable exposures such as smoking and has been associated with respiratory health conditions. However, the effect of emerging toxicants, particularly engineered nanoparticles, alone or in co-exposure with smoking, is poorly understood. Here, we investigated the impact of sub-chronic exposure to carbon nanotube (CNT) particles, cigarette smoke extract (CSE), and their combination. The oral, nasal, and lung microbiomes were characterized using 16S rRNA-based metagenomics. The exposures caused the following shifts in lung microbiota: CNT led to a change from Proteobacteria and Bacteroidetes to Firmicutes and Tenericutes; CSE caused a shift from Proteobacteria to Bacteroidetes; and co-exposure (CNT+CSE) had a mixed effect, maintaining higher numbers of Bacteroidetes (due to the CNT effect) and Tenericutes (due to the CSE effect) compared to the control group. Oral microbiome analysis revealed an abundance of the following genera: Acinetobacter (CNT), Staphylococcus, Aggregatibacter, Allobaculum, and Streptococcus (CSE), and Alkalibacterium (CNT+CSE). These proinflammatory microbial shifts correlated with changes in the relative expression of lung mucosal homeostasis/defense proteins, viz., aquaporin 1 (AQP-1), surfactant protein A (SP-A), mucin 5b (MUC5B), and IgA. Microbiota depletion reversed these perturbations, albeit to a varying extent, confirming the modulatory role of oro-respiratory dysbiosis in lung mucosal toxicity. This is the first demonstration of specific oro-respiratory microbiome constituents as potential modifiers of toxicant effects in exposed lungs.

Assessment of managed aquifer recharge in saline confined aquifers for freshwater storage and improved recovery: A 3D tank study under various operational conditions.

Aquifer Storage and Recovery (ASR), a subset of Managed Aquifer Recharge (MAR) techniques, is a promising technique to address water scarcity issues by recharging depleted aquifers. The application of ASR in saline groundwater regions is challenging due to mixing of recharged freshwater with the ambient saline groundwater, decreasing the recoverable amount of freshwater. This paper aimed to investigate the feasibility of ASR techniques for freshwater storage and recovery in saline confined aquifers using a laboratory scale physical model (100 cm length x 30 cm width x 60 cm depth). The study then explored the impact of operational factors (freshwater storage duration, injected freshwater volume, number of injection/extraction cycles etc.) on freshwater recovery from an applied ASR. Firstly, the behaviour of stored freshwater in a saline-confined aquifer was investigated, and in the next step, the impact of ASR operational parameters on the recovery efficiency (RE) was evaluated. Along with the physical model, these effects were studied using a mathematical model (MODFLOW linked with SEAWAT) for the representative aquifer system. The movement and spreading of the stored freshwater were monitored over time. The experimental results presented in this study suggested that several factors significantly influence the efficiency of ASR systems. A negative correlation between ambient groundwater salinity and average recovery efficiency (ARE) was confirmed, with decreasing ARE observed as the salinity level increased. The injection volume of freshwater was found to have a positive influence on ARE, although the relationship was non-linear, a polynomial trend was observed. The longer freshwater was stored in the aquifer, the lower ARE was reported, indicating a negative impact of storage duration on ASR performance. Finally, the number of successive cycles of ASR operation was found to have a positive influence on ARE, but the effect decreased with each subsequent cycle. This research provided valuable insights into the application of ASR techniques for freshwater storage and its enhanced recovery in saline confined aquifers.

Does the peroral chromium administration in young Hariana calves reduce the risk of calf diarrhea by ameliorating insulin response, lactose intolerance, antioxidant status, and immune response?

BACKGROUND: The reduction in insulin sensitivity during rumen development may predispose dairy calves towards lactose intolerance, which could be the reason behind neonatal calf diarrhea (NCD). Chromium (Cr) results in a range of effects when fed to ruminants, but most studies have shown improved insulin sensitivity. The aim of this study was to determine the effect of Cr supplementation on insulin sensitivity, lactose intolerance, diarrhoea and antioxidant, and immune response in young Hariana calves. METHODS: A total of 20 milk-fed Hariana calves were randomly assigned to 1 of 2 treatments, each consisted of 10 calves: (1) a control group without supplemental Cr and (2) a 0.15 mg Cr as Cr-picolinate (CrPic)/kg BW0.75 supplemented group (Cr0.15). RESULTS: A more rapid glucose disappearance with unaltered insulin kinetics during intravenous glucose tolerance test (IVGTT) and oral lactose tolerance test (OLTT) indicates greater insulin sensitivity in Cr supplemented calves. Better insulin sensitivity in Cr supplemented calves was further confirmed by higher values of the quantitative insulin sensitivity check index (QUICKI), revised quantitative insulin sensitivity check index (RQUICKI) and insulin receptor substrate-1 (IRS-1) and lower (P < 0.05) values of homeostasis model assessment-insulin resistance (HOMA-IR) and glucose-to-insulin ratio in Cr supplemented calves during IVGTT. Cr supplementation resulted in a lower (P < 0.05) serum cortisol concentration, whereas serum non-esterified fatty acid (NEFA) concentrations during IVGTT did not differ among the groups. The rise in serum glucose concentrations within 2 h post lactose infusion during OLTT peaked at more than twice the basal glucose concentration, therefore calves were not considered as lactose intolerant. Within monthly blood samples, concentrations of serum insulin were similar among treatments, whereas the Cr supplemented group had lower (P < 0.05) serum glucose concentration and glucose-to-insulin ratio compared with the control group. No treatment differences were detected in the biomarkers of antioxidant status and immunity. Serum Cr concentrations were higher (P < 0.05) in Cr supplemented calves while concentrations of other studied minerals were remained unaltered. The incidence, duration of diarrhea, and faecal score were better (P < 0.05) in calves fed on Cr supplemented diet whereas, no treatment effect was observed on average daily gain (ADG). During the study period, no calves died, and no calves were found to have pneumonia, navel or joint disease. CONCLUSION: Feeding a Cr-supplemented diet improved insulin sensitivity and reduced the risk of diarrhoea in milk-fed young calves, but had no or minimal effects on lactose intolerance, antioxidant status, immune response, and growth performance.

Higher pro-inflammatory cytokines IL-6 and IFN-γ are associated with anti-SARS-CoV-2 spike protein-specific seroconversion in renal allograft recipients.

BACKGROUND: Maintenance immunosuppressive regimens are speculated to hamper immunogenic response against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) in renal transplant recipients (RTRs) compared to the healthy population. Healthy people with SARS-CoV-2 infection often develop neutralizing antibodies and secret copious quantities of cytokines, leading to virus clearance and sometimes more severe immune-related complications. METHODS: RTRs, either acquired SARS-CoV-2 infection (infection group, n = 132) or were vaccinated with two vaccine doses (vaccination group, n = 78) against SARS-CoV-2, were recruited in the study. Thirty-five unvaccinated RTRs, without anti-SARS-CoV-2 spike protein-specific antibodies, were also included as control. Cytokines interleukine-6 (IL-6), interferon-γ (IFN-γ), TGF-ß, and IL-10 were measured using ELISA. The SARS-CoV-2 spike protein-specific IgG-titer was measured by chemiluminescent microparticle immunoassay methods. RESULTS: The seroconversion rate in the infection group was 115/132 (87.12%), with a median antibody titer 706.40 au/mL (IQR, 215.45-1844.42), and in the vaccination group was 63/78 (80.76%) with antibody titer 1454.20 au/mL (IQR, 80.52-3838.75). The IL-6, IFN-γ, TGF-ß, and IL-10 levels were significantly higher in both the infection and vaccination group compared to healthy control. In the infection group, pro-inflammatory cytokines IL-6 (55.41 ± 24.30 vs. 31.64 ± 16.98 pg/mL, p < .001) and IFN-γ (91.21 ± 33.09 vs. 61.69 ± 33.28 pg/mL, p = .001) were significantly higher in the seroconverter group as compared to non-seroconverter. Similarly, in the vaccination group, pro-inflammatory cytokines IL-6 (50.31 ± 25.67 vs. 30.00 ± 11.19 pg/mL; p = .002) and IFN-γ (65.70 ± 39.78 vs. 32.14 ± 17.48 pg/mL; p = .001) were significantly higher in the seroconverter group compared to non-seroconverter. In contrast, TGF-ß (820.96 ± 415.78 vs. 1045.57 ± 204.66; p = .046) was higher in non-seroconverter. CONCLUSIONS: Pro-inflammatory cytokines IL-6 and IFN-γ were significantly associated with seroconversion after SARS-CoV-2 infection and vaccination in RTRs.

Renal injury, biomarkers, and myositis, an understudied aspect of disease: prospective study in the MyoCite cohort.

Introduction: The mechanisms leading to chronic kidney disease (CKD) in patients with idiopathic inflammatory myopathies (IIMs) are poorly understood. We assessed the prevalence of subclinical renal injury in patients with IIMs, through elevation in biomarker levels of tubular injury and fibrosis (NGAL, KIM1, Activin A, CD163, and Cys-c), and assessed differences between subtypes of IIMs, and the effect of disease activity and duration. Materials and methods: Clinical data, core set measures, sera and urine were prospectively collected from all patients enrolled in the MyoCite cohort from 2017 to 2021. Twenty healthy subjects (HC) and 16 patients with acute kidney injury (AKI) were included as controls. Baseline and follow up data for IIMs were included. Enzyme-linked immunosorbent assay (ELISA) was used to measure urine NGAL (Human Lipocalin-2/NGAL Duoset ELISA, Cat no: DY1757), KIM1 (Human TIM-1/KIM 1/HAVCR Duoset ELISA, Cat.no: DY1750B), Activin A (Human Activin A Duoset ELISA, Cat no: DY338), CD163 (Human CD163 Duoset ELISA,Cat no: DY1607-05), and Cys-c (Human Cystatin C Duoset ELISA, Cat. no.: DY1196) levels, while eGFR (unit mL/min/1.73 m2) was calculated by the Cockcroft-Gault formula and CKD-EPI formula. Results: Analysis of 201 visits of 110 adult patients with IIMs indicated higher normalized biomarker levels compared to HCs, and comparable to patients with AKI, with the exception of NGAL, which was higher in the AKI group. Notably 72 (49%) patients with IIMs had eGFR<90; the levels of the 5 biomarkers were comparable between active and inactive IIMs, and different subtypes of IIMs. Similarly, a poor correlation between urine biomarker levels and core set measures of activity and damage was found. Changes in biomarker levels on follow-up did not correlate with eGFR changes. Discussion: This exploratory analysis of urinary biomarkers identified low eGFR and elevated biomarkers of CKD in nearly half of the patients with IIMs, comparable to patients with AKI and higher than HCs, indicative of potential renal damage in IIMs that may have a lead to complications in other systems.

Lower Circulating Cytotoxic T-Cell Frequency and Higher Intragraft Granzyme-B Expression Are Associated with Inflammatory Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Recipients.

Background and Objectives: Inflammatory interstitial fibrosis and tubular atrophy (i-IFTA) is an inflammation in the area of tubular atrophy and fibrosis. i-IFTA is poorly associated with graft outcome and associated with infiltration of inflammatory mononuclear cells. A cytotoxic T cell is a granzyme B+CD8+CD3+ T cell, mainly secret granzyme B. Granzyme B is a serine protease that may mediate allograft injury and inflammatory interstitial fibrosis and tubular atrophy (i-IFTA). However, there is no report identifying the association of granzyme B with i-IFTA after a long post-transplant interval. Material and Methods: In this study, we have measured the cytotoxic T-cell frequency with flow cytometry, serum and PBMCs culture supernatants granzyme-B levels with ELISA and intragraft granzyme-B mRNA transcript expression with the RT-PCR in RTRs in 30 patients with biopsy-proven i-IFTA and 10 patients with stable graft function. Result: The frequency of cytotoxic T cells (CD3+CD8+ granzyme B+) in SGF vs. i-IFTA was (27.96 ± 4.86 vs. 23.19 ± 3.85%, p = 0.011), the serum granzyme-B level was (100.82 ± 22.41 vs. 130.32 ± 46.60, p = 0.038 pg/mL) and the intragraft granzyme-B mRNA transcript expression was (1.01 ± 0.048 vs. 2.10 ± 1.02, p < 0.001 fold). The frequency of CD3+ T cells in SGF vs. i-IFTA was (66.08 ± 6.8 vs. 65.18 ± 9.35%; p = 0.68) and that of CD3+CD8+ T cells was (37.29 ± 4.11 vs. 34.68 ± 5.43%; p = 0.28), which were similar between the 2 groups. CTLc frequency was negatively correlated with urine proteinuria (r = -0.51, p < 0.001), serum creatinine (r = -0.28, p = 0.007) and eGFR (r = -0.28, p = 0.037). Similarly, the PBMC culture supernatants granzyme-B level was negatively correlated with urine proteinuria (r = -0.37, p < 0.001) and serum creatinine (r = -0.31, p = 0.002), while the serum granzyme-B level (r = 0.343, p = 0.001) and intragraft granzyme-B mRNA transcript expression (r = 0.38, p < 0.001) were positively correlated with proteinuria. Conclusions: A decrease in the CTLc frequency in circulation and an increased serum granzyme-B level and intragraft granzyme-B mRNA expression shows that cytotoxic T cells may mediate the allograft injury in RTRs with i-IFTA by releasing granzyme B in serum and intragraft tissue.

Identification of Natural Compounds of the Apple as Inhibitors against Cholinesterase for the Treatment of Alzheimer's Disease: An In Silico Molecular Docking Simulation and ADMET Study.

Alzheimer's disease (AD), the most common type of dementia in older people, causes neurological problems associated with memory and thinking. The key enzymes involved in Alzheimer's disease pathways are acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Because of this, there is a lot of interest in finding new AChE inhibitors. Among compounds that are not alkaloids, flavonoids have stood out as good candidates. The apple fruit, Malus domestica (Rosaceae), is second only to cranberries regarding total phenolic compound concentration. Computational tools and biological databases were used to investigate enzymes and natural compounds. Molecular docking techniques were used to analyze the interactions of natural compounds of the apple with enzymes involved in the central nervous system (CNS), acetylcholinesterase, and butyrylcholinesterase, followed by binding affinity calculations using the AutoDock tool. The molecular docking results revealed that CID: 107905 exhibited the best interactions with AChE, with a binding affinity of -12.2 kcal/mol, and CID: 163103561 showed the highest binding affinity with BuChE, i.e., -11.2 kcal/mol. Importantly, it was observed that amino acid residue Trp286 of AChE was involved in hydrogen bond formation, Van Der Walls interactions, and Pi-Sigma/Pi-Pi interactions in the studied complexes. Moreover, the results of the Molecular Dynamics Simulation (MDS) analysis indicated interaction stability. This study shows that CID: 12000657 could be used as an AChE inhibitor and CID: 135398658 as a BuChE inhibitor to treat Alzheimer's disease and other neurological disorders.

Antioxidant additive melatonin in tris-based egg yolk extender improves post-thaw sperm attributes in Hariana bull.

In the study, melatonin, a known antioxidant pineal peptide was used as an additive in the tris-egg yolk glycerol-based semen extender in Hariana bull semen and post-thaw sperm characters were evaluated. In the study, Group I was a control without melatonin; and Group II, III, and IV were having 0.5 mM, 1 mM, and 2 mM melatonin/80 × 106 spermatozoa, respectively were treatment groups. Thirty-two semen ejaculates from 4 Hariana bulls were processed for freezing and post-thaw sperm characteristics were evaluated. Sperm motility, velocity, the viability with intact membrane, and total antioxidant capacity were markedly (P < 0.05) improved in Group IV compared to all other groups. The lipid peroxidation and total protein carbonylation were substantially (P < 0.05) decreased in Group IV compared to all other groups. The population of cryocapacitated, acrosome-reacted, and apoptotic-like spermatozoa were significantly (P < 0.05) decreased in Group IV. Further, the relative band intensity of 74 kDa protein and percent of spermatozoa showing positive immune reactivity to tyrosine-phosphorylated proteins was decreased in Group IV. The progesterone-receptor ligand binding, in vitro capacitation response, and Vanguard distance were markedly (P < 0.05) improved in Group IV. In summary- Group IV having 2 mM melatonin was found to be optimal in providing cryoprotective effects to Hariana bull spermatozoa after freezing-thawing and can be suitably used as a semen additive during semen cryopreservation.

Antibody response to ChAdOx1 nCoV-19 (Covishield®) vaccine in people on maintenance hemodialysis.

INTRODUCTION: People on renal replacement therapy (RRT) have a high risk of COVID-19 infection and subsequent death. COVID-19 vaccination is strongly recommended for those on RRT. Data are limited on the immune response of the ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine in patients on RRT. METHODS: A prospective cohort of adult (age > 18 years), on RRT in the form of hemodialysis were included and received two intramuscular doses of Covishield®. A blood specimen of 5.0 mL was collected at two time points, within a few days before administering the first dose of the vaccine and at 4-16 weeks after the second dose. According to their prior COVID-19 infection status, the participants were grouped as (i) prior symptomatic COVID-19 infection, (ii) prior asymptomatic COVID-19 infection, and (iii) no prior COVID-19 infection. RESULTS: A large proportion (81%) of participants had anti-spike antibodies (ASAb) before vaccination, and a reasonable proportion (30%) also had neutralizing antibodies (NAb). The titer of ASAb was relatively low (207 U/mL) before vaccination. The ASAb titer (9405 [1635-25,000] U/mL) and percentage of NAb (96.4% [59.6-98.1%]) were markedly increased following the administration of two doses of the vaccine. The participants' prior COVID-19 exposure status did not influence the rise in ASAb titer and NAb percentage. Further, administering two doses of the Covishield vaccine helps them achieve a high ASAb titer. CONCLUSION: Two doses of ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine, given 12 weeks apart, achieve a high titer of ASAb and a high percentage of NAb in people on hemodialysis.

Diverse begomovirus-betasatellite complexes cause tomato leaf curl disease in the western India.

In the Indian sub-continent, tomato leaf curl disease (ToLCD) of tomato caused by begomoviruses has emerged as a major limiting factor for tomato cultivation. Despite the spread of this disease in the western India, a systematic study on the characterization of virus complexes with ToLCD is lacking. Here, we report the identification of a complex of begomoviruses including 19 DNA-A and 4 DNA-B as well as 15 betasatellites with ToLCD in the western part of the country. Additionally, a novel betasatellite and an alphasatellite were also identified. The recombination breakpoints were detected in the cloned begomoviruses and betasatellites. The cloned infectious DNA constructs cause disease on the tomato (a moderately virus-resistant cultivar) plants, thus fulfilling Koch's postulates for these virus complexes. Further, the role of non-cognate DNA B/betasatellite with ToLCD-associated begomoviruses on disease development was demonstrated. It also emphasizes the evolutionary potential of these virus complexes in breaking disease resistance and plausible expansion of its host range. This necessitates to investigate the mechanism of the interaction between resistance breaking virus complexes and the infected host.

Ligand-based designing of DPP-4 inhibitors via hybridization; synthesis, docking, and biological evaluation of pyridazine-acetohydrazides.

A series of novel pyridazine-acetohydrazide hybrids were designed, synthesized, and evaluated for their in vitro and in vivo antihyperglycemic activity. In this context, pyridazine-acetohydrazides (6a-6p) were synthesized by coupling substituted aldehyde with 2-(5-cyano-6-oxo-3,4-diphenylpyridazine-1-6H-yl) acetohydrazide, which was prepared via the reaction of pyridazine ester with hydrazine hydrate. The molecular docking study was carried out to examine the binding affinities and interaction of designed compounds against the DPP-4 enzyme. Compounds 6e, 6f, 6l, and 6n exhibited interaction with active residue. In silico ADMET properties, and toxicity studies corroborated that compounds were found to have good bioavailability and less toxic. The synthesized compounds were further estimated for in vitro DPP-4 activity. Compounds 6e and 6l were found as the most effective DPP-4 inhibitor in this series with IC50 values (6.48, 8.22 nM) when compared with sitagliptin (13.02 nM). According to the toxicity assay compound, 6l showed very less toxicity at a higher concentration so further selected for the in vivo antihyperglycemic activity.

Application of analytical hierarchical process, multi-influencing factor, and geospatial techniques for groundwater potential zonation in a semi-arid region of western India.

Groundwater resources are alarmingly depleting due to over-exploitation and significant climate changes over time. Therefore, demarcation of groundwater potential zones is essential for addressing the needs of various industries in semi-arid area. Depleting groundwater resources, topography, aquifer features and climatic factors make it necessary to demarcate ground water potential zones in semiarid region of Rajasthan. The Analytical Hierarchy Process (AHP), Geographic Information System (GIS), and Multi Influence Factor (MIF) were used to determine the groundwater potential zones (GWPZs) in the semi-arid region of Jaipur, located in western Rajasthan. In present study, ten influential factors were employed i.e., geomorphology, land use/land cover (LULC), drainage density, rainfall, topographic wetness index (TWI), soil texture, slope, roughness, topographic position index (TPI) and curvature. In AHP technique, the pairwise comparison matrix was generated, and weightages were given to each thematic layer while for MIF, a proposed score for each layer was computed from the aggregate weight of major and minor effects. The GWPZ map generated by AHP technique was categorised into three parts: high, moderate and poor potential zones, covering 13%, 50.7% and 36.3% of the district. While, the GWPZ map produced with the MIF technique was also divided into the same poor, moderate, and high categories, encompassing 35.3, 44.1, and 20.6% of the district, respectively. The results of AHP and MIF techniques were then cross-validated with well depth data obtained from CGWB report, 2019-20. The receiver operating characteristics (ROC) were plotted and the findings shows that the Area under the Curve (AUC) was 79% and 76% for AHP and MIF, respectively which is considered as moderate to high in predictive precision. The study would be helpful in locating drilling sites for groundwater exploration and developing sustainable groundwater and land use policies.

Prevalence of the Direct Antiglobulin Test and Its Clinical Impact on Multiply Transfused Thalassemia Patients: A Prospective Study Conducted at a Tertiary Care Center in Northern India.

OBJECTIVE: This study was conducted to estimate prevalence of direct antiglobulin test (DAT) positivity and its impact on transfusion support in patients with thalassemia. METHODS: The DAT testing was performed for patients with ß-thalassemia who received transfusion from November 2021 to March 2022. Elution was done for DAT-positive samples. RESULTS: Of 180 patients, 21 (11.6%) were DAT positive. Immunoglobulin G (IgG) was present in 4 (19%) and IgG+C3d was present in 8 (38%). Only complement was present in 9 (42.8%) patients. The IgG-reactive DATs were associated with pan-reactive eluate. Patients who were DAT-positive had significantly higher levels of serum bilirubin, ferritin, and IgG than those who were DAT-negative. CONCLUSION: Autoantibody formation in multiply transfused thalassemia patients is common and merits equal attention as alloimmunization. It is particularly important as DAT-positive red blood cells may undergo clinically significant hemolysis, which may increase the transfusion requirements with associated sequalae such as increased serum ferritin and splenomegaly.

Red cell alloimmunization and associated risk factors in multiply transfused thalassemia patients: A prospective cohort study conducted at a tertiary care center in Northern India.

BACKGROUND: One of the complications of chronic transfusions in thalassemia is the development of red cell alloimmunization. AIMS: The aim of the study was to determine the frequency, specificity of red cell alloantibodies, and factors influencing alloimmunization in multiply transfused thalassemia patients. MATERIALS AND METHODS: The study was carried out prospectively on beta-thalassemia patients over 10 months. Plasma samples were used for antibody screening and identification using the column agglutination technique. Patients' clinical, laboratory, and transfusion details were obtained from hospital information system and patient files. STATISTICAL ANALYSIS: Continuous variables were reported as median and quartile, whereas categorical variables were provided as numbers and proportions. P < 0.05 was considered statistically significant. RESULTS: Out of 255 patients, 17 (6.6%) patients developed alloantibodies. Alloimmunized patients had significantly higher median ages at their first transfusions (1 year vs. 0.5 years; P = 0.042) than nonalloimmunized patients. Alloimmunized patients had significantly higher conjugated bilirubin (P = 0.016) and serum ferritin (P = 0.007). The majority of alloantibodies had specificity toward K antigen, followed by E, C, D, JKa, and JKb antigens. Alloimmunized patients received more units per year than nonalloimmunized patients (median, 30 vs. 24 units; P < 0.001). The average transfusion interval time between two successive transfusions showed a significant difference (P < 0.001). CONCLUSIONS: The prevalence of alloimmunization in thalassemia patients in North India is relatively low. Since most of the alloantibodies belong to Rh and Kell blood group system, extended phenotype-matched blood for Rh and Kell will be helpful in further preventing or decreasing the development of alloantibodies in multiply transfused thalassemia patients.

Effect of donor parameters and cell separators on yield of apheresis platelet and their impact on corrected count increment in aplastic anemia patients.

BACKGROUND: The new cell separators make it simple to collect single donor platelets (SDP), although the platelet yield may vary depending on the cell separator used and donor-related clinical and laboratory variables. AIMS: This study aims to study the factors affecting SDP yield and corrected count increment (CCI). MATERIALS AND METHODS: This retrospective study was carried out at a tertiary care facility in northern India, over 4 years (May 2017-April 2020), data were retrieved and analyzed. STATISTICAL ANALYSIS: Categorical variables were presented as proportions, while continuous variables were presented as mean with standard deviation, P < 0.05 was considered significant. RESULTS: We found a positive correlation between predonation platelet count and yield (r = 0.243, P = 0.000). No such significant correlation was found with Hb concentration (r = 0.025, P = 0.720), age (r = 0.016, P = 0.820), sex (r = -0.038, P = 0.584), and weight (r = -0.025, P = 0.714). Maximum platelet yield and minimum time were seen with Trima. Only 39.3% (33/84) meet the 24 h CCI. The majority of patients did not meet the desired CCI could be due to the patients' clinical condition. On logistic regression, we found a significant association of 24 h CCI with product yield (odds ratio [OR] = 0.168, P = 0.015) and posttransfusion platelet count (OR = 0.454, P < 0.05). CONCLUSION: The only donor-related factor that influences yield is predonation platelet count, whereas 24 h CCI may depend on the clinical status of the patient and yield.

Association of Human Leucocyte Antigen Polymorphism with Coronavirus Disease 19 in Renal Transplant Recipients.

Human leucocyte antigens (HLAs) are highly polymorphic glycoproteins expressed at the surface of all nucleated cells. It is required for the SARS-CoV-2 peptide antigen presentation to immune cells for their effector response. However, polymorphism in HLA significantly impacts the binding of SARS-CoV-2 antigenic peptide to the HLA pocket and regulates immune activation. In this study, 514 renal transplant recipients (RTRs) were recruited from the outpatient department and categorized either into symptomatic (n = 173) or asymptomatic groups (n = 341) based on Coronavirus disease-19 (COVID-19) symptoms. The anti-SARS-CoV-2 spike protein-specific IgG antibody titer was measured by chemiluminescent microparticle immune-assay methods in 310 RTRs. The HLA details of 514 patients were retrieved from the electronic medical records and analyzed retrospectively. We found that HLA antigen allele A*24 was significantly associated with asymptomatic infection in 22.78%, HLA C*02 in 4.51%, DRB1*12 in 10.85%, and HLA DQA1*02 in 27.74% of RTRs. Whereas HLA A*29 in 3.46%, A*33 in 26.01%, B*13 in 10.40%, DRB1*10 in 4.62%, DRB1*15 in 39.30%, DRB1*30 in 1.15%, and DQA1*60 in 3.57% of RTRs were associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease. The seroconversion rate in asymptomatic patients was 118/137 (86.13%), had a median titer of 647.80 au/ml, compared to symptomatic patients 148/173 (85.54%) with a median titer of 400.00 au/ml, which was not significant between the two groups (P = 0.88 and 0.13). In conclusion, HLA alleles A*24, C*02, DRB1*12, and DQA1*02 were significantly associated with asymptomatic infection, and A*29, A*33, B*13, DRB1*10, DRB*15, and DRB1*30 were significantly associated with symptomatic infection. HLA DRB1*13 and DRB1*15 were associated with moderate to severe degrees of COVID-19 disease.

Antibody Response to ChAdOx1 nCoV-19 (AZD1222) Vaccine in Kidney Transplant Recipients.

Kidney transplant recipients (KTRs) are at a much higher risk of complications and death following COVID-19 and are poor vaccine responders. The data are limited on the immune response to Covishield® in KTRs. We prospectively recruited a cohort of 67 KTRs aged >18 between April 2021 and December 2021. Each participant was given two intramuscular doses of Covishield®, each of 0.5 mL, at an interval of 12 weeks. A blood specimen of 5.0 mL was collected from each participant at two points within a few days before administering the first dose of the vaccine and at any time between 4−12 weeks after administering the second dose. The sera were tested for anti-RBD antibody (ARAb) titre and neutralising antibody (NAb). An ACE2 competition assay was used as a proxy for virus neutralization. According to the prior COVID-19 infection, participants were grouped as (i) group A: prior symptomatic COVID-19 infection, (ii) group B: prior asymptomatic COVID-19 infection as evidenced by detectable ARAb in the prevaccination specimen, (iii) Group C: no prior infection with COVID-19, (iv) group D: Unclassified, i.e., participants had no symptoms suggestive of COVID-19, but their prevaccination specimen was not available for ARAb testing before vaccination. Fifty of sixty-seven participants (74.6%) provided paired specimens (group A 14, group B 27, and group C 9) and 17 participants (25.4%) provided only postvaccination specimens (group D). In the overall cohort (n = 67), 91% and 77.6% of participants developed ARAb and NAb, respectively. Their ARAb titre and NAb proportion were 2927 (520−7124) U/mL and 87.9 (24.4−93.2) %, respectively. Their median ARAb titre increased 65.6 folds, from 38.2 U/mL to 3137 U/mL. Similarly, the proportion of participants with NAb increased from 56% to 86%, and the NAb proportion raised 2.7 folds, from 23% to 91%. A comparison of vaccine response between the study groups showed that all those with or without prior COVID-19 infection showed a significant rise in ARAb titre (p < 0.05) and NAb proportion (p < 0.05) after the two doses of vaccine administration. The median value of folds rise in anti-RBD and NAb between groups A and B were comparable. Hence, ARAb is present in more than 3/4th of KTRs before the ChAdOx1 vaccine in India. The titer of ARAb and the proportion of NAb significantly increased after the two doses of the ChAdOx1 vaccine in KTRs.