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1.
Chemosphere ; 354: 141591, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38460846

ABSTRACT

The sustainable utilization of resources motivate us to create eco-friendly processes for synthesizing novel carbon nanomaterials from waste biomass by minimizing chemical usage and reducing energy demands. By keeping sustainability as a prime focus in the present work, we have made the effective management of Parthenium weeds by converting them into carbon-based nanomaterial through hydrothermal treatment followed by heating in a tube furnace under the nitrogen atmosphere. The XPS studies confirm the natural presence of nitrogen and oxygen-containing functional groups in the biomass-derived carbon. The nanostructure has adopted a layered two-dimensional structure, clearly indicated through HRTEM images. Further, the nanomaterials are analyzed for their ability towards the electrochemical detection of mercury, with a detection limit of 6.17 µM, while the limit of quantification and sensitivity was found to be 18.7 µM and 0.4723 µM µA-1 cm-2, respectively. The obtained two-dimensional architecture has increased the surface area, while the nitrogen and oxygen functional groups act as an active site for sensing the mercury ions. This study will open a new door for developing metal-free catalysts through a green and sustainable approach by recycling and utilization of waste biomass.


Subject(s)
Biosensing Techniques , Mercury , Nanostructures , Parthenium hysterophorus , Biosensing Techniques/methods , Nanostructures/chemistry , Carbon/chemistry , Ions , Nitrogen/chemistry , Oxygen
2.
Haemophilia ; 30(2): 410-418, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38343110

ABSTRACT

INTRODUCTION: Various risk factors for inhibitor development in haemophilia A (HA) have been described but Indian data remains scanty. AIM: We aimed to evaluate the genetic changes in Indian HA-patients that are associated with the development of inhibitors. METHODS: All HA-patients with inhibitors who availed coagulation-laboratory services from January-2015 till December-2021 and had their samples preserved for DNA extraction were included in this study. An equal number of severity-matched HA patients without inhibitors were also included as controls. Intron 22 and intron 1 inversions in Factor VIII gene were identified using inverse-shifting-PCR. Inversion-negative patients were further assessed by targeted NGS, MLPA. RESULTS: Thirty HA-patients with inhibitors were identified. All had severe-HA. Thirty severe-HA-patients without inhibitors were also included as controls. Intron 22 inversion (63.3%) and large deletions (15%) were the commonest variants identified. There was no difference in genetic variants in patients with low and high titre inhibitors. A3, A2 and C2 were the most common domains involved in inversion-negative patients with inhibitors. However, there was no significant difference in domain involvement among inversion-negative patients with and without inhibitors. Seven novel-variants were identified, including three large deletions, one large duplication and two nonsense variants in inhibitor-positive patients, and one frameshift variant in inhibitor-negative patient. After adjusting for clinical risk-factors, large deletions were independently associated with the presence of inhibitors [aOR:6.1 (1.41-56.3)]. CONCLUSION: Intron 22 inversions are the commonest variant in Indian patients with severe-HA. Large deletions predispose to inhibitor development independent of clinical risk factors.


Subject(s)
Hemophilia A , Humans , Hemophilia A/genetics , Cohort Studies , Factor VIII/genetics , Genetic Association Studies , Introns , Chromosome Inversion , Genotype , Phenotype , Mutation
3.
Water Sci Technol ; 89(3): 513-528, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38358486

ABSTRACT

In the current study, a novel methylene blue (MB)-based colorimetric method for a quick, inexpensive, and facile approach for the determination of fouling intensity of reverse osmosis (RO) membrane has been reported. This technique is based on the interaction of MB with the organic foulants and shows the corresponding change in the colour intensity depending on the severity of fouling. The organic foulants, such as albumin, sodium alginate, and carboxymethyl cellulose (CMC), were chosen as model foulants, and the membranes were subjected to foul under extreme fouling conditions. The fouled membranes underwent an MB treatment followed by image-processing analyses. The severity of surface fouling of membranes was evaluated in terms of fouling intensity and correlated with the corresponding decline of permeate flux. The maximum fouling intensity of the albumin, sodium alginate, and CMC sodium were found to be 8.83, 23.38, and 9.19%, respectively, for the definite concentration of foulants. The physico-chemical interactions of the given foulants and MB were confirmed by changes in zeta potentials and increased sizes of the foulant by the dynamic light scattering technique. The surface fouling over the membrane surface was confirmed by the characterization of membranes.


Subject(s)
Colorimetry , Methylene Blue , Albumins , Alginates , Carboxymethylcellulose Sodium , Osmosis
5.
ACS Appl Mater Interfaces ; 16(6): 7097-7111, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38296332

ABSTRACT

The incorporation of cerium-zinc bimetallic oxide (CeZnOx) nanostructures in sulfonated poly(2,6-dimethyl-1,4-phenylene oxide) (SPPO) membranes holds promise in an enhanced and durable fuel cell performance. This investigation delves into the durability and efficiency of SPPO membranes intercalated with CeZnOx nanostructures by varying the filler loading of 1, 2, and 3% (w/w). The successful synthesis of CeZnOx nanostructures by the alkali-aided deposition method is confirmed by wide-angle X-ray diffraction spectroscopy (WAXS), Raman spectroscopy, field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) analyses. CeZnOx@SPPO nanocomposite membranes are fabricated using a solution casting method. The intricate interplay of interfacial adhesion and coupling configuration between three-dimensional CeZnOx and sulfonic moieties of the SPPO backbone yields an enhancement in the bound water content within the proton exchange membranes (PEMs). This constructs simultaneously an extensive hydrogen bonding network intertwined with the proton transport channels, thereby elevating the proton conductivity (Km). The orchestrated reversible redox cycling involving Ce3+/Ce4+ enhances the quenching of aggressive radicals, aided by Zn2+, promoting oxygen deficiency and Ce3+ concentration. This synergistic efficacy ultimately translates into composite PEMs characterized by a mere 4% mass loss and a nominal 6% decrease in Km after rigorous exposure to Fenton's solution. Remarkably, an improved power density of 403.2 mW/cm2 and a maximum current density of 1260.6 mA/cm2 were achieved with 2% loading of CeZnOx (SPZ-2) at 75 °C and 100% RH. The fuel cell performance of SPZ-2 is 74% higher than its corresponding pristine SPPO membrane.

6.
Chemosphere ; 346: 140653, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37949185

ABSTRACT

This study uses waste coconut husk to synthesize carbon quantum dots decorated graphene-like structure for sustainable detection and removal of ofloxacin. The XRD spectrum shows the carbon nanomaterial's layered structure with turbostratic carbon stacking on its surface. The FESEM and HRTEM studies claim the successful development of quantum dots decorated 2D layered structure of carbon nanomaterial. The functionalization of sulfur and nitrogen is well observed and studied through XPS, while Raman spectra have provided insight into the surface topology of the as-synthesized nanostructure. The BET surface area was found to be 1437.12 m2/g with a microporous structure (pore width 2.0 nm) which interestingly outcompete many reported carbon-based nanomaterials such as graphene oxide, reduced graphene oxide and quantum dots. The detection and removal processes are monitored through UV-visible spectroscopy and the obtained detection limit and adsorption capacity were 2.7 nM and 393.94 mg/L respectively. Additionally, 1 mg carbon nanomaterial has removed 49 % ofloxacin from water in just 1 h. In this way, this study has successfully managed the coconut husk waste after its utilization for environmental remediation purposes.


Subject(s)
Carbon , Nanostructures , Carbon/chemistry , Cocos , Nitrogen/chemistry , Sulfur
7.
Blood Cell Ther ; 6(4): 124-128, 2023 Nov 25.
Article in English | MEDLINE | ID: mdl-38149023

ABSTRACT

Introduction: While there are data about return to work after hematopoietic cell transplantation (HCT) in survivors from resource-rich regions, similar data from resource-challenged settings are scarce. This study assessed the incidence of and factors affecting return to work/school (RTW) among HCT survivors in India. Methods: This single-center cross-sectional study was conducted at the long-term follow-up (LTFU) clinic of a large-volume HCT center during 2022-2023. HCT survivors surviving beyond four months were included after obtaining informed consent. Patients' sociodemographic, disease, HCT, and work details were recorded. The factors affecting RTW were evaluated using univariate (ANOVA) and logistic regression analyses. Results: A total of 126 HCT survivors participated in the study. Of these, 34 (27%) did not RTW, 47 (37%) returned to part-time work, and 45 (36%) returned to full-time work at a median of more than three years post-HCT. The three groups did not significantly differ in age, sex, or marital status. The univariate analysis revealed that education, pre-HCT job status, income, and conditioning intensity were significantly associated with RTW. Logistic regression analysis revealed that survivors with a higher (taxable) income were more likely to RTW than those with a lower (non-taxable) income (OR 3.5; CI 1.2-10.2, p=0.01). Survivors with a desk job were more likely to RTW than those who were unemployed/retired or students (OR 4.5; CI 1.1-18.0, p=0.03). Conclusion: Socioeconomic factors, like pre-HCT job status and income, were significantly associated with post-HCT RTW. Therefore, there is a need to integrate multidisciplinary RTW programs for HCT survivors in India.

8.
Cureus ; 15(7): e42559, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37637646

ABSTRACT

This review article provides a comprehensive overview of the current state of mental health in India, highlighting the challenges faced, the existing initiatives, and the future directions for improving mental healthcare delivery. India is grappling with a high prevalence of mental health disorders, including depression, anxiety disorders, bipolar disorder, schizophrenia, and substance use disorders. The burden of mental health issues on individuals, families, and society is immense, leading to reduced quality of life, impaired functioning, and significant economic and social consequences. Various social and cultural factors, such as stigma, discrimination, gender inequalities, poverty, rapid urbanization, and cultural beliefs surrounding mental illness, further exacerbate the challenges of addressing mental health problems. Access to mental healthcare remains a significant concern, with considerable gaps in access to and quality of treatment and limited availability of mental health professionals, especially in rural areas. Inadequate infrastructure, a lack of awareness, and insufficient integration into primary healthcare systems hinder access to appropriate care. The historical development of mental asylums in India is examined, highlighting their establishment, purpose, and evolution over time. Critiques and challenges associated with mental asylums are discussed, including stigmatization, human rights concerns, the absence of human center approaches, quality of care, and the need for alternative approaches to mental healthcare.

9.
Mitochondrion ; 71: 83-92, 2023 07.
Article in English | MEDLINE | ID: mdl-37269968

ABSTRACT

Misfolded proteins in the central nervous system can induce oxidative damage, which can contribute to neurodegenerative diseases in the mitochondria. Neurodegenerative patients face early mitochondrial dysfunction, impacting energy utilization. Amyloid-ß and tau problems both have an effect on mitochondria, which leads to mitochondrial malfunction and, ultimately, the onset of Alzheimer's disease. Cellular oxygen interaction yields reactive oxygen species within mitochondria, initiating oxidative damage to mitochondrial constituents. Parkinson's disease, linked to oxidative stress, α-synuclein aggregation, and inflammation, results from reduced brain mitochondria activity. Mitochondrial dynamics profoundly influence cellular apoptosis via distinct causative mechanisms. The condition known as Huntington's disease is characterized by an expansion of polyglutamine, primarily impactingthe cerebral cortex and striatum. Research has identified mitochondrial failure as an early pathogenic mechanism contributing to HD's selective neurodegeneration. The mitochondria are organelles that exhibit dynamism by undergoing fragmentation and fusion processes to attain optimal bioenergetic efficiency. They can also be transported along microtubules and regulateintracellular calcium homeostasis through their interaction with the endoplasmic reticulum. Additionally, the mitochondria produce free radicals. The functions of eukaryotic cells, particularly in neurons, have significantly deviated from the traditionally assigned role of cellular energy production. Most of them areimpaired in HD, which may lead to neuronal dysfunction before symptoms manifest. This article summarizes the most important changes in mitochondrial dynamics that come from neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and Amyotrophic Lateral Sclerosis. Finally, we discussed about novel techniques that can potentially treat mitochondrial malfunction and oxidative stress in four most dominating neuro disorders.


Subject(s)
Alzheimer Disease , Amyotrophic Lateral Sclerosis , Huntington Disease , Neurodegenerative Diseases , Parkinson Disease , Humans , Parkinson Disease/pathology , Alzheimer Disease/pathology , Huntington Disease/metabolism , Amyotrophic Lateral Sclerosis/pathology , Oxidative Stress/physiology , Neurodegenerative Diseases/metabolism , Mitochondria/metabolism
10.
Curr Pediatr Rev ; 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37317913

ABSTRACT

Unhealthy pregnancy and the resultant abnormalities in newborns exhibit a significant drawback. Each year, an estimated 15 million babies are born prematurely, accounting for the majority of deaths among children under the age of 5. India accounts for about a quarter of all preterm birth (PTB) incidences, with few therapeutic options available. However, research shows that consuming more marine foods (rich in omega-3 fatty acids (Ω-3), particularly Docosahexaenoic acid (DHA), helps to maintain a healthy pregnancy and can manage or prevent the onset of PTB and its accompanying difficulties. Present circumstances raise concerns about the use of DHA as a medication due to a lack of evidence on the dosage requirements, safety profile, molecular route, and commercially accessible strength for their therapeutic response. Several clinical experiments have been done over the last decade; however, the mixed outcomes have resulted in discrepancies. Most scientific organizations suggest a daily DHA consumption of 250-300 mg. However, this may differ from person to person. As a result, before prescribing a dosage, one should check the DHA concentrations in the individual's blood and then propose a dose that will benefit both the mother and the unborn. Thus, the review focuses on the favourable benefits of Ω-3, particularly DHA during pregnancy and postpartum, therapeutic dose recommendations, safety considerations, particularly during pregnancy, and the mechanistic pathway that might prevent or reduce the frequency of PTB accidents.

13.
Environ Res ; 231(Pt 2): 116151, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37196695

ABSTRACT

Parthenium hysterophorus, one of the seven most hazardous weeds is widely known for its allergic, respiratory and skin-related disorders. It is also known to affect biodiversity and ecology. For eradication of the weed, its effective utilization for the successful synthesis of carbon-based nanomaterial is a potent management strategy. In this study, reduced graphene oxide (rGO) was synthesized from weed leaf extract through a hydrothermal-assisted carbonization method. The crystallinity and geometry of the as-synthesized nanostructure are confirmed from the X-ray diffraction study, while the chemical architecture of the nanomaterial is ascertained through X-ray photoelectron spectroscopy. The stacking of flat graphene-like layers with a size range of ∼200-300 nm is visualized through high-resolution transmission electron microscopy images. Further, the as-synthesized carbon nanomaterial is advanced as an effective and highly sensitive electrochemical biosensor for dopamine, a vital neurotransmitter of the human brain. Nanomaterial oxidizes dopamine at a much lower potential (0.13 V) than other metal-based nanocomposites. Moreover, the obtained sensitivity (13.75 and 3.31 µA µM-1 cm-2), detection limit (0.6 and 0.8 µM), the limit of quantification (2.2 and 2.7 µM) and reproducibility calculated through cyclic voltammetry/differential pulse voltammetry respectively outcompete many metal-based nanocomposites that were previously used for the sensing of dopamine. This study boosts the research on the metal-free carbon-based nanomaterial derived from waste plant biomass.


Subject(s)
Carbon , Dopamine , Humans , Dopamine/chemistry , Reproducibility of Results , Electrochemical Techniques/methods , Metals , Plant Extracts
14.
Indian J Hematol Blood Transfus ; 39(2): 276-283, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37006978

ABSTRACT

Purpose: The study aimed to explore the molecular defects underlying FXIII deficiency. Materials and Methods: Sixteen unrelated cases were enrolled based on the indication of the urea clot solubility test and Factor XIII-A antigen levels. Cases were further subjected to targeted next-generation sequencing (custom gene panel: F7, F8, VWF, F9, F13A1, F13B). The pathogenic/likely pathogenic variants were validated by Sanger sequencing in the patients and family members. Results: Mean age of referral to our center was 27.2 years (8 week-67 years). Consanguinity was found in only one of the 16 cases and 9 cases presented in infancy. The most common symptoms were skin bleeds (69%) and umbilical cord bleed (50%). The clot solubility test was positive in 12, inconclusive in 1, and normal in 3. Mean FXIII-A levels were 15.7 IU/dL (range 0.6 to 49.5 IU/dL). Pathogenic/likely pathogenic variants in F13A1 were found in 11 (69%). Nine cases (82%) were homozygous, and two were compound heterozygous. Total eleven variants were found of which four were missense (c.1226G>A; c.998C>T; c.631G>C; c.2134A>C); three deletion (c.521delG; c.742delA; c.1405_1408delCAAA); two nonsense (c.1112G>A; c.1127G>A) and two splice site (c.1909-1G>C; c.2045G>A). No probably pathogenic variant was found in the F13B. Conclusion: Inherited FXIII deficiency with bleeding is associated with genetic defects in predominantly the F13A1 gene. A variety of variants were seen in this cohort. A nonsense variant c.1127G>A found in three of our cases seems to be recurrent. This data will contribute to designing functional studies and antenatal testing in affected families. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01579-1.

15.
Environ Res ; 229: 115922, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37086886

ABSTRACT

The inflated demand for plastic products has led to tremendous rise in plastic debris in different environmental matrices, thereby resulting in plastic pollution. This affects plants, animals, and even humans, as microplastics can enter the food chain and cause several health implications. Microplastics are the small plastic particles (size below 5 mm) that are largely debated nowadays owing to their environmental risk assessment. Their potential to interact with other toxic contaminants, their tendency to be ingested or taken up by living organisms and their longevity is a serious threat to our environment. However, despite wealth of recent information, still there is a gap, particularly in eco-toxicology studies, fate, prevalence and feasible solutions to cope up with the menace of microplastics pollution. This review unravels the environmental fate and behaviour of microplastics as well as their global distribution in the marine and terrestrial environment. Furthermore, we aim to contribute to the international debate on the microplastics global paradigm. We briefly suggest sustainable solutions and recommendations to achieve future research goals on microplastics. Our review reveals some of the newest biological (green algae and modified sponges) and physical (nano-particles and membrane treatment) remediation solutions to eradicate microplastics from different types of environment. This review presents a critical evaluation of the state of knowledge of micro-plastics and suggested some recommendations which can help in identifying some important key questions for future research.


Subject(s)
Microplastics , Water Pollutants, Chemical , Animals , Humans , Microplastics/toxicity , Plastics/toxicity , Prevalence , Water Pollutants, Chemical/analysis , Environmental Pollution , Environmental Monitoring , Ecosystem
16.
Int J Biol Macromol ; 234: 123484, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-36731704

ABSTRACT

Gliadin, owing to its low cost, ease to extract, high foaming capacity, easily available and high surface hydrophobicity, has found a wide range of applications both in the food and pharmaceutical sectors. The functional and structural characteristics of gliadin extracted with four extraction protocols from six wheat cultivars were investigated in this study. The surface-active properties of gliadin protein as a function of pH, extraction protocols, and wheat cultivars were compared, including solubility, zeta-potential, foaming properties, emulsion properties, surface hydrophobicity and secondary structure. Overall gliadin extracted using different extraction protocols and from different wheat cultivars was found to be higher in ß-turns (24.88-37.91 %), followed by ß-sheet (12.81-22.37 %), α-helix (15.13-20.70 %) and lower in random coil (6.53-9.08 %). Varied pH ranges, wheat cultivars, and different extraction protocols were found to have a substantial impact on solubility, zeta potential, foaming stability, emulsion capacity and surface hydrophobicity. The foaming capacity was observed to be more influenced by extraction protocols than wheat cultivars. Emulsion stability showed statistically significant (p ≤ 0.05) influence between the wheat cultivars, and a non-significant (p ≥ 0.05) difference among extraction protocols. The functional properties of freeze-dried gliadin extracted using different protocols were found to be pH-dependent. A comprehensive understanding of how the structural, surface active and functional properties of gliadin are influenced by the extraction protocols and wheat cultivars will enable us to understand the gliadin better and broaden its use for both food and non-food applications.


Subject(s)
Gliadin , Triticum , Gliadin/chemistry , Triticum/chemistry , Emulsions/chemistry , Hydrophobic and Hydrophilic Interactions , Hydrogen-Ion Concentration
17.
PLoS One ; 18(1): e0279616, 2023.
Article in English | MEDLINE | ID: mdl-36656815

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer's sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer's disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity. RESULT: In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex's dynamic development. CONCLUSION: As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD.


Subject(s)
Alzheimer Disease , Bromocriptine , Claviceps , Intracranial Aneurysm , Toll-Like Receptor 4 , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Bromocriptine/pharmacology , Intracranial Aneurysm/prevention & control , Molecular Docking Simulation , Toll-Like Receptor 4/metabolism , Triticum/microbiology
18.
Environ Res ; 217: 114844, 2023 01 15.
Article in English | MEDLINE | ID: mdl-36403653

ABSTRACT

Poly- and perfluoroalkyl substances (PFAS) are a class of emerging organic contaminants that are impervious to standard physicochemical treatments. The widespread use of PFAS poses serious environmental issues. PFAS pollution of soils and water has become a significant issue due to the harmful effects of these chemicals both on the environment and public health. Owing to their complex chemical structures and interaction with soil and water, PFAS are difficult to remove from the environment. Traditional soil remediation procedures have not been successful in reducing or removing them from the environment. Therefore, this review focuses on new phytoremediation techniques for PFAS contamination of soils and water. The bioaccumulation and dispersion of PFAS inside plant compartments has shown great potential for phytoremediation, which is a promising and unique technology that is realistic, cost-effective, and may be employed as a wide scale in situ remediation strategy.


Subject(s)
Fluorocarbons , Water Pollutants, Chemical , Biodegradation, Environmental , Fluorocarbons/analysis , Water , Bioaccumulation , Soil/chemistry , Water Pollutants, Chemical/analysis
19.
Haemophilia ; 29(2): 591-599, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36571800

ABSTRACT

INTRODUCTION: Inherited Factor VII (FVII) deficiency is commonest among the rare bleeding disorders. A small number of patients present in infancy with severe bleeding, and many may remain asymptomatic but detected before surgery/invasive procedures. Genetic testing may be helpful in predictive testing/prenatal diagnosis in severe cases. AIM: Characterisation of clinical and genotypic spectrum of patients with inherited FVII deficiency. METHODS: Retro-prospectively, 35 cases with prolonged prothrombin time and FVII activity (FVII:C) <50 IU/dl were subjected to targeted resequencing. After in-silico analysis, variant/s were validated by Sanger sequencing in index cases and family members. Haplotype analysis was done for F7 polymorphisms. RESULTS: Severe FVII deficiency was found in 50% of patients (FVII:C ≤1 IU/dl), and 42.9% were asymptomatic. Clinical severity assessment revealed 17% severe, 17% moderate and 22.9% patients with mild bleeds. FVII levels ranged from .3 to 38 IU/dl. Molecular analysis revealed variants in 30/35 cases, of which 17 were homozygous, 10 were compound heterozygous and 3 were heterozygous. Twelve genetic variants were identified, one promoter variant c.-30A>C; seven missense (c.215C>G, c.244T>C, c.253G>C, c.904G>A, c.961C>T, c.1109G>T, c.1211G>A), two deletions (c.21delG, c.868_870delATC), and one each of nonsense c.634C>T and splice-site variant c.316+1G>A. Recurrent variants c.1109G>T and c.215C>G were found in 17 and 8 cases, 12 of the former cases were homozygous. They had the same haplotype, indicating the founder effect in North Indians. CONCLUSION: This is the largest cohort of FVII genotyping from India, confirming heterogeneity in terms of clinical manifestations, FVII activity and zygosity of the variants with a limited genotypic phenotypic correlation.


Subject(s)
Blood Coagulation Disorders , Factor VII Deficiency , Humans , Founder Effect , Mutation , Factor VII Deficiency/diagnosis , Factor VII Deficiency/genetics , Factor VII/genetics , Hemorrhage
20.
J Biomol Struct Dyn ; 41(1): 1-15, 2023 01.
Article in English | MEDLINE | ID: mdl-34796791

ABSTRACT

Dengue and zika are amongst the most prevalent mosquito-borne diseases caused by closely related members Dengue virus (DENV) and Zika virus (ZIKV), respectively, of the Flaviviridae family. DENV and ZIKV have been reported to co-infect several people, resulting in fatalities across the world. A vaccine that can safeguard against both these pathogens concurrently, can offer several advantages. This study has employed immuno-informatics for devising a multi-epitope, multi-pathogenic vaccine against both these viruses. Since, the two viruses share a common vector source, whose salivary components are reported to aid viral pathogenesis; antigenic salivary proteins from Aedes aegypti were also incorporated into the design of the vaccine along with conserved structural and non-structural viral proteins. Conserved B- and T-cell epitopes were identified for all the selected antigenic proteins. These epitopes were merged and further supplemented with ß-defensin as an adjuvant, to yield an immunogenic vaccine construct. In-silico 3D modeling and structural validation of the vaccine construct was conducted, followed by its molecular docking and molecular dynamics simulation studies with human TLR2. Immune simulation study was also performed, and it further provided support that the designed vaccine can mount an effective immune response and hence provide protection against both DENV and ZIKV. Communicated by Ramaswamy H. Sarma.


Subject(s)
Dengue Virus , Dengue , Vaccines , Zika Virus Infection , Zika Virus , Animals , Humans , Zika Virus Infection/prevention & control , Dengue/prevention & control , Molecular Docking Simulation , Epitopes, T-Lymphocyte
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