Determination of uranium isotopes in ground water by alpha spectrometry and associated age-dependent ingestion dose.

Determination of uranium isotopes in ground water plays a key role in assessment of geochemical condition of ground water and for estimating ingestion dose received by the general public because of uranium intake through drinking water. An attempt has been made in the present study to estimate isotopic composition and activity ratios (AR) of uranium isotopes by analysing the ground water samples using alpha spectrometry. Associated age-dependent ingestion dose was also calculated for the public of different age groups. 238U, 235U and 234U activity concentration was found to vary in the ranges of 5.85 ± 1.19 to 76.67 ± 4.16, < 0.90 to 3.15 ± 0.84 and 6.52 ± 1.25 to 107.02 ± 4.92 mBq/L, respectively. 235U/238U AR varies from 0.038 to 0.068 with an average of 0.047 which is close to 0.046 implies that uranium in the ground water is from natural origin. Uranium concentration was found to vary in the range of 0.47 ± 0.10 µg/L to 6.20 ± 0.34 µg/L with a mean value of 3.01 ± 0.23 µg/L, which is much lower than national as well as international recommendation value. Annual ingestion dose to the public of all age groups for uranium intake through drinking water ranges from 0.60 ± 0.11 to 19.50 ± 1.03 µSv/y.

Radiation dose due to uranium in groundwater to the population of Chamarajanagar district, Karnataka, India.

This paper presents the concentration of uranium in 67 groundwater samples of Chamarajanagar district, Karnataka, India, estimated using an LED fluorimeter. The age-dependent ingestion dose to the population of the district is also studied. The concentration of uranium in groundwater varied from 0.20 to 57.50 µg L-1 with an average of 4.40 µg L-1. The annual ingestion dose due to uranium varies from 0.18 to 142.68 µSv y-1, with an average of 7.11 µSv y-1. The ingestion dose received by the population in the study area is less than the recommended level of 100 µSv y-1 by the World Health Organization (2011).

Fibrosis and bone marrow: understanding causation and pathobiology.

Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. The present review consolidates current understanding of marrow fibrosis. We searched PubMed without time restriction using key words: bone marrow and fibrosis as the main stem against the terms: growth factors, cytokines and chemokines, morphology, megakaryocytes and platelets, myeloproliferative disorders, myelodysplastic syndrome, collagen biosynthesis, mesenchymal stem cells, vitamins and minerals and hormones, and mechanism of tissue fibrosis. Tissue marrow fibrosis-related papers were short listed and analysed for the review. It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. Megakaryocytes and platelets are either directly involved or are important intermediaries in stimulating mesenchymal stem cells. MMPs, TIMPs, TGF-ß, PDGRF, and basic FGF and CRCXL4 chemokines are involved in these processes. Genetic and epigenetic changes underlie many of these conditions.

Poisson Counts, Square Root Transformation and Small Area Estimation: Square Root Transformation.

The paper intends to serve two objectives. First, it revisits the celebrated Fay-Herriot model, but with homoscedastic known error variance. The motivation comes from an analysis of count data, in the present case, COVID-19 fatality for all counties in Florida. The Poisson model seems appropriate here, as is typical for rare events. An empirical Bayes (EB) approach is taken for estimation. However, unlike the conventional conjugate gamma or the log-normal prior for the Poisson mean, here we make a square root transformation of the original Poisson data, along with square root transformation of the corresponding mean. Proper back transformation is used to infer about the original Poisson means. The square root transformation makes the normal approximation of the transformed data more justifiable with added homoscedasticity. We obtain exact analytical formulas for the bias and mean squared error of the proposed EB estimators. In addition to illustrating our method with the COVID-19 example, we also evaluate performance of our procedure with simulated data as well.

Hydrolytically stable citrate capped Fe3O4@UiO-66-NH2 MOF: A hetero-structure composite with enhanced activity towards Cr (VI) adsorption and photocatalytic H2 evolution.

Design and facile fabrication of a magnetically separable hetero-structure photocatalyst as well as an adsorbent having dual green benefits towards energy conversion and pollutant remediation are quite indispensable in the current scenario. In this regard, a composite of citrate capped Fe3O4 and UiO-66-NH2 has been designed to remediate Cr (VI) by adsorption and harvest photons from visible light for clean energy (H2) conversion. The material was prepared by the union of citrate capped Fe3O4 (CCM) and versatile aqueous stable Zr-based MOF (UiO-66-NH2) through in-situ solvothermal method. The composite of CCM with MOF (MU-2) was studied through sophisticated analysis techniques; PXRD, FT-IR, BET, UV-Visible DRS, PL, TG, HRTEM and XPS etc. to reveal the inherent characteristics of the material. BET surface analysis revealed high specific surface area (572.13 m2 g-1) of MU-2 in comparison to its pristine MOF. Furthermore, the dual function composite MU-2's VSM studies showed that its magnetic saturation is 3.07 emu g-1 that is suitable for magnetic separation after desired reaction from aqueous media. The Cr (VI) sorption studies revealed that the composite adsorbent (MU-2) showed maximum monolayer adsorption capacity (Qm) of 743 mg g-1 which followed pseudo second order kinetics. Moreover, the sorption thermodynamics revealed that the process was spontaneous and endothermic in nature. In addition to it, the synthesized composite material displayed enhanced activity towards photocatalytic H2 evolution with a maximum evolution rate of 417 µmole h-1 with an apparent conversion efficiency (ACE) of 3.12 %. Typically, MU-2 displays high adsorptions of Cr (VI) as well as some extent of Cr (VI) reduction owning to its populous active sites and free carboxylate groups respectively. Moreover, the synergistic effect of CCM and UNH in the composite resulted in Z scheme mediated charge transfer mechanism that showed enhanced H2 photo-evolution rates. Hence, MU-2 can be readily utilized as magnetically retrievable dual function composite for Cr (VI) adsorption and photocatalytic H2 evolution.

Role of Glycerol Oxidation Pathways in the Reductive Acid Leaching Kinetics of Manganese Nodules Using Glycerol.

Manganese nodules from ocean bed are potential resources of Cu, Ni, and Co for which land-based deposits are scarce in India. The present work describes a novel approach of using glycerol, a nontoxic biomass-derived reductant, for the reductive acid leaching of manganese nodules. Parameters such as acid concentration, time, temperature, and pulp density were optimized for leaching. The optimal leaching conditions were found to be 10% (w/v) pulp density and 10% (v/v) H2SO4 at 80 °C with 1% (v/v) glycerol yielding >95% of Ni and >98% Cu, Co, and Mn extraction within an hour. Kinetic analysis of the data based on the initial rate method showed that the leaching process was chemical reaction-controlled with an apparent activation energy of 55.47 kJ/mol. Various oxidation intermediates of glycerol formed during leaching were identified using mass spectrometry and Raman spectroscopy, and a probable oxidation pathway of glycerol during the leaching process has been elucidated based on the analysis. Glycerol was oxidized to glyceraldehyde, glyceric acid, tartronic acid, dihydroxyacetone, hydroxy pyruvic acid, glyoxalic acid, oxalic acid, and finally converted to CO2 during leaching. The fast reaction kinetics, near-complete dissolution of manganese, and other associated metals in the nodule can be attributed to the participation of all intermediate products of glycerol oxidation in redox reactions with MnO2, enhancing the overall reduction leaching efficiency.

Thrombohaemorhhagic balance in coronavirus disease 2019 and its management: a perspective.

Coronavirus disease 2019 infection produce a prothrombotic state. This is initiated through multiple pathways and is finally aggravated by cross talks with cytokine storm and neutrophil, platelet, complement activation. All these combine towards the second week of illness to produce thrombosis in the lung capillaries surrounding the alveolus producing characteristic pulmonary dysfunction (PaO2/FiO2 > 300, normal or minimally increased lung compliance and very high d-dimer levels) and a high rate of peripheral venous thrombosis. International and many national guidelines have approached this state in different ways but all emphasized the need for management and prevention of widespread thrombosis. It is felt more aggressive and graded thrombosis prevention and management should be initiated early in the treatment. d-Dimer, neutrophil count, SaO2, fibrinogen levels should be used to control the hypercoagulability. Drugs like statins which have anti-inflammatory action as well as ability to reduce fibrinogen and other clotting factors should be used in the beginning along with antiplatelet drugs and progressively complement activation and neutrophil extracellular traps inhibitors, oral mucopolysaccharides, full-scale anticoagulation along with judicial use of fibrinolysis supporting drugs should be added. In the present review, we have evaluated the various studies and argued the rationality that the anticoagulation in this condition should be initiated early during the infection and should be increased in a graded manner depending on clinical and laboratory progression of the condition until a strong specific antiviral drug for coronavirus disease 2019 infection is available.

Process Flowsheet Development for Separation of Sm, Co, Cu, and Fe from Magnet Scrap.

A complete process flowsheet to recover metal values from Sm2Co17-type magnet scrap was investigated. The magnet scrap was leached in chloride medium at pulp density of 2% (w/v) under the optimum conditions of 15% (v/v) HCl and 5% (v/v) H2O2 at 70 °C for 3 h, which yielded 98.5% Sm and 99% Co extractions. The full factorial Design of Experiment technique was adopted for the optimization of leaching conditions. Sm was selectively separated from the leach liquor as precipitated double salt using Na2SO4. The precipitated double sulfate was later converted to Sm-oxalate, which was subsequently calcined to produce pure Sm2O3. Following Sm separation, Fe was removed through precipitation by raising the pH to 3.0. For Cu and Co recovery, solvent extraction techniques using LIX 84I and Na-CYANEX 272, respectively, were followed. The McCabe-Thiele diagrams for extraction as well as stripping were presented for both Cu and Co.

Efficacy of Dichlorophenolindophenol (DCIP) as Screening Test for Hb E: Revisited.

Hb E-beta thalassemia is a major public health problem in West Bengal, India and is the predominant symptom producing thalassemia in this part of the country. To search for an easy, reliable and cost effective screening method for HbE that can be used at the community level where more sophisticated methods are not readily available. And the DCIP test was performed for the purpose. Blood samples of 425 asymptomatic family members from 80 diagnosed cases of HbE beta Thalassemia patients were tested for Hb, RBC indices, DCIP test, HPLC, and in discordant cases confirmed by DNA mutation analysis. The present study shows DCIP screening test to have a sensitivity, specificity, positive predictive value and negative predictive value of 96.39%, 97.43%, 96.39% and 97.43% respectively. It also shows a false positive rate and false negative rate in 2.56% and 4.6% cases respectively. The advantage with DCIP over HPLC is that it can be easily performed at the community level by a person with minimum technical skill, few samples (even a single sample) can be tested at time, at a low cost.

Sustainable Process for the Extraction of Potassium from Feldspar Using Eggshell Powder.

To recover potassium from feldspar, a biowaste, i.e., eggshell, was used. The chief composition of eggshells is calcite. As it is a rich source of Ca, hence it is used with HCl to produce calcium chloride. Feldspar is an aluminosilicate mineral that bears potassium in the interstitial sites. To unlock the potassium from the interstitial sites, it was roasted with calcium chloride prepared by mixing eggshell and hydrochloric acid. At the roasting temperature, CaCl2 melts and penetrates into the aluminosilicate matrix to replace K with Ca. Potassium ion released from the silicate matrix combines with chloride ions to form potassium chloride, which solubilized in water during the leaching process of the roasted feldspar. For elucidation of the mechanism of the roasting process, the shrinking core model was applied to the roast-leach data, and diffusion through the product layer was inferred as the rate-determining step. The order of the roasting process was found to be 2.158 and activation energy calculated to be 155.3 kJ/mol. Apart from potassium, sodium and excess calcium also got co-leached. To recover potassium from the leach liquor selectively, sodium perchlorate was added to precipitate potassium as KClO4. Further, potassium perchlorate was thermally decomposed to give fertilizer grade potassium chloride (purity: 99.81%).

Molecular interactions of MnO2@RGO (manganese dioxide-reduced graphene oxide) nanocomposites with bovine serum albumin.

Graphene based materials have attracted global attention due to their excellent properties. GO-metal oxide nanocomposites have been conjugated with biomolecules for the development of novel materials and potentially used as biomarkers. Herein, a detailed study on the interaction of Bovine serum albumin (BSA) with MnO2@RGO (manganese dioxide-reduced graphene oxide) nanocomposites (NC) has been carried out. MnO2@RGO nanocomposites were prepared through a template/surfactant free hydrothermal route at 180 °C for 12 h by varying the graphene oxide (GO) concentration. Different biophysical experiments have been carried out to evaluate molecular interactions between BSA and NCs. Intrinsic fluorescence has been used to quantify the quenching efficiency of NCs and the binding association of BSA-NC complexes. NCs effectively quenched the intrinsic fluorescence of BSA via static and dynamic mechanism. Further, the results indicate that the molecular interactions of NC with BSA are dependent on the GO percentage in NC. Circular dichroism results demonstrate nominal changes in the secondary structure of BSA in presence of NCs. Also, the esterase-like activity of BSA was marginally affected after adsorption upon NCs. In addition, the FESEM micrographs reveal that the protein-NC complexes consist of nanorod and sheet-like morphologies are forming aggregates of different sizes. We hope that this study will provide a basis for the design of novel graphene based and other related nanomaterials for several biological applications.Communicated by Ramaswamy H. Sarma.

Inherited Macrothrombocytopenia: Correlating Morphology, Epidemiology, Molecular Pathology and Clinical Features.

Inherited macrothrombocytopenia is increasingly being recognized as a relatively common condition. This descriptive review aims at focusing on the different areas of advancement that have taken place with this condition with particular reference to India. A pubmed search of articles between January 1990 and October 2017 with the key words-macrothrombocytopenia, asymptomatic macrothrombocytopenia, macrothrombocytopenia India, syndromic macrothrombocytopenia, molecular pathology, megakaryopoiesis and platelet formation were searched. The shortlisted articles were then read. Review articles provided additional references and the articles thus obtained were also read. Special interest and research conducted by the authors provided further sources of information. A total of 487 articles were found of which 68 articles were related to our subject of review. Review articles were read and additional articles from the reference quoted. Forty-four percent of nonsyndromic Inherited macrothrombocytopenia showed mutations of MYH9, GP1BB, GP1Ba, GPIX, ABCG5 and 8, ACTN, FLI, TUBB and RUNX1 frequently in heterozygous state. All types of inheritance pattern namely autosomal dominant, recessive and sex linked patterns have been described. Syndromic causes of this phenomenon are well known and have been described. Many asymptomatic patients do have mild or moderate bleeding history. Clinical algorithms to differentiate chronic ITP associated macrothrombocytopenia from inherited variety have been explored. Inherited macrothrombocytopenia is an emerging area of interest in platelet biology with its implication in diagnosis, prognosis, genetic counseling, management and in transfusion medicine.

A Novel Selective Soluble Guanylate Cyclase Activator, MGV354, Lowers Intraocular Pressure in Preclinical Models, Following Topical Ocular Dosing.

Purpose: The nitric oxide/soluble guanylate cyclase/protein kinase G (NO/sGC/PKG) is known to be involved in the regulation of intraocular pressure (IOP) and may be dysregulated in glaucoma. The purpose is to demonstrate that the sGC activator MGV354 lowers IOP in a monkey model of glaucoma and could be considered as a possible new clinical drug candidate. Methods: Changes to cGMP were assessed in primary human trabecular meshwork (hNTM) cells and binding studies were conducted using human sGC full-length protein. Ocular safety tolerability, exposure, and efficacy studies were conducted in rabbit and monkey models following topical ocular dosing of MGV354. Results: sGC was highly expressed in the human and cynomolgus monkey outflow pathways. MGV354 had a 7-fold greater Bmax to oxidized sGC compared to that of reduced sGC and generated an 8- to 10-fold greater cGMP compared to that of a reduced condition in hTM cells. A single topical ocular dose with MGV354 caused a significant dose-dependent reduction of 20% to 40% (versus vehicle), lasting up to 6 hours in pigmented rabbits and 24 hours postdose in a cynomolgus monkey model of glaucoma. The MGV354-induced IOP lowering was sustained up to 7 days following once-daily dosing in a monkey model of glaucoma and was greater in magnitude compared to Travatan (travoprost)-induced IOP reduction. Mild to moderate ocular hyperemia was the main adverse effect noted. Conclusions: MGV354 represents a novel class of sGC activators that can lower IOP in preclinical models of glaucoma. The potential for sGC activators to be used as effective IOP-lowering drugs in glaucoma patients could be further determined in clinical studies.

The Discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (Acrizanib), a VEGFR-2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for Neovascular Age-Related Macular Degeneration.

A noninvasive topical ocular therapy for the treatment of neovascular or "wet" age-related macular degeneration would provide a patient administered alternative to the current standard of care, which requires physician administered intravitreal injections. This manuscript describes a novel strategy for the use of in vivo models of choroidal neovascularization (CNV) as the primary means of developing SAR related to efficacy from topical administration. Ultimately, this effort led to the discovery of acrizanib (LHA510), a small-molecule VEGFR-2 inhibitor with potency and efficacy in rodent CNV models, limited systemic exposure after topical ocular administration, multiple formulation options, and an acceptable rabbit ocular PK profile.

A Blockwise Consistency Method for Parameter Estimation of Complex Models.

The drastic improvement in data collection and acquisition technologies has enabled scientists to collect a great amount of data. With the growing dataset size, typically comes a growing complexity of data structures and of complex models to account for the data structures. How to estimate the parameters of complex models has put a great challenge on current statistical methods. This paper proposes a blockwise consistency approach as a potential solution to the problem, which works by iteratively finding consistent estimates for each block of parameters conditional on the current estimates of the parameters in other blocks. The blockwise consistency approach decomposes the high-dimensional parameter estimation problem into a series of lower-dimensional parameter estimation problems, which often have much simpler structures than the original problem and thus can be easily solved. Moreover, under the framework provided by the blockwise consistency approach, a variety of methods, such as Bayesian and frequentist methods, can be jointly used to achieve a consistent estimator for the original high-dimensional complex model. The blockwise consistency approach is illustrated using two high-dimensional problems, variable selection and multivariate regression. The results of both problems show that the blockwise consistency approach can provide drastic improvements over the existing methods. Extension of the blockwise consistency approach to many other complex models is straightforward.

Does Profile of Hemoglobin Eß-thalassemia Patients Change After Splenectomy? Experience of a Tertiary Thalassemia Care Centre in Eastern India.

Hemoglobin Eß-thalassemia is by far the commonest form of thalassemia intermedia. Its phenotype ranges from mild anemia to severe transfusion-dependency necessitating splenectomy in many patients. The present study aimed to systematically analyze both clinical as well as laboratory parameters in profile of Eß-thalassemia patients after splenectomy in terms of transfusion requirement, infections and other complications. Retrospective study conducted over a period of 3 years included 72 cases of splenectomized Eß-thalassaemia patients, considering decrease in transfusion requirements, new complications, antibiotic, anti-malarial prophylaxis and iron chelation therapy. Out of 1380 registered Eß-thalassemia patients, 618 (44.78 %) were regularly transfused and 72(5.22 %) underwent splenectomy. Mean age of diagnosis was 10.3 years. Nineteen patients (26.4 %) underwent splenectomy between 5 and 10 years, 38 cases (52.7 %) between 10 and 20 years. The leading cause (51.39 %) for splenectomy was mechanical discomfort. Mean steady state hemoglobin raised from pre-splenectomy level of 5.43-6.8 gm/dl after splenectomy. Mean transfusion requirement reduced from 18.1 to 7.8 units/year. Mean serum ferritin level increased from 907.58 to 1,091.6 ng/ml. Post-splenectomy; 21 (29.17 %) patients developed facial deformities, 17 (23.6 %) delayed pubertal growth, 11 (15.28 %) venous thromboembolism, five (6.94 %) pulmonary hypertension and four (5.5 %) had extramedullary hematopoiesis. Five (6.96 %) patients had documented bacterial infections and two (2.78 %) suffered from malaria. Forty eight patients (66.67 %) started with iron chelation therapy; but majority (52.7 %) stopped. Major advantage of splenectomy is reduced transfusion requirement, though it cannot prevent skeletal abnormalities and delayed pubertal growth. In resource constraint countries like India, routine anti-malarial and antibacterial prophylaxis is not desirable; iron chelation therapy should be encouraged and ensured.

Effectiveness of Prenatal Screening for Hemoglobinopathies in a Developing Country.

The thalassemias are among the most common monogenic diseases worldwide, a national health burden in India. There are estimated 7500-12,000 babies born with ß-thalassemia major (ß-TM) every year in this country. Couples who are at-risk of having children with hemoglobin (Hb) disorders desired to have the option of avoiding the birth of an affected child by prenatal diagnosis (PND). Thus, the prenatal women are a highly important target group for carrier screening and preventing the birth of thalassemic children in the country. The present study was conducted among 20,883 pregnant women, irrespective of gravida and duration of pregnancy, from the prenatal clinic of Nilratan Sarkar (NRS) Medical College & Hospital, Kolkata, West Bengal, India, from February 2009 to November 2012. Thalassemia carrier status was assessed by high performance liquid chromatography (HPLC) along with red blood cell (RBC) indices. Husbands of all thalassemia carrier women were advised and persuaded to undergo screening for hemoglobinopathies. The couples were counseled to undergo PND if both of them were detected to be thalassemia carriers. The data were statistically analyzed to evaluate the efficacy of this procedure.

Guidelines for screening, diagnosis and management of hemoglobinopathies.

The ß-thalassemias and sickle cell disorders are a major health burden in India. Diagnosis and management of these disorders both in adults and in newborns using appropriate approaches and uniform technology are important in different regions of a vast and diverse country as India. In view of a National Thalassemia Control Program to be launched soon, a need was felt for guidelines on whom to screen, cost-effective technologies that are to be used as well as for establishing prenatal diagnosis programs in regional centers. Newborn screening for sickle cell disorders is in its infancy in India and uniform approaches need to be followed. Also, included are guidelines for monitoring and managing patients who are now growing older and need comprehensive care as well as management of complications of the disease.

Interaction of iron deficiency anemia and hemoglobinopathies among college students and pregnant women: a multi center evaluation in India.

Although iron deficiency anemia is very common in India, systematic large studies on the prevalence and hematological consequences of iron deficiency among carriers of ß-thalassemia (ß-thal) and other hemoglobinopathies are lacking. A multi center project was undertaken to screen college/university students and pregnant women for iron deficiency anemia and various hemoglobinopathies. Fifty-six thousand, seven hundred and seventy-two subjects from six states, Maharashtra, Gujarat, Karnataka, West Bengal, Assam and Punjab, were studied. Iron deficiency anemia was evaluated by measuring zinc protoporphyrin (ZPP) and hemoglobin (Hb) levels, while ß-thal and other hemoglobinopathies were detected by measuring the red cell indices and by Hb analysis using high performance liquid chromatography (HPLC). College boys (2.2%), college girls (14.3%) and antenatal women (27.0%) without any hemoglobinopathies had iron deficiency anemia. Among the ß-thal carriers, the prevalence of iron deficiency anemia was 17.3% in college boys, 38.1% in college girls and 55.9% in pregnant women, while in the Hb E [ß26(B8)Glu→Lys; HBB: c.79G>A] carriers, it was 7.3% in college boys, 25.4% in college girls and 78.0% in antenatal women. In individuals with Hb E disease, the prevalence of iron deficiency anemia varied from 31.2-77.3% in the three groups. A significant reduction in Hb levels was seen when iron deficiency anemia was associated with hemoglobinopathies. However, the Hb A2 levels in ß-thal carriers were not greatly reduced in the presence of iron deficiency anemia.