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1.
J Mol Neurosci ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170714

RESUMO

Cohen syndrome (CS) is an autosomal recessive congenital disorder, characterized by hypotonia, intellectual disability, developmental delay, microcephaly, progressive retinopathy, neutropenia, truncal obesity, joint laxity, characteristic facial, ophthalmic, oral and appendage abnormalities, and an over friendly behavior. It has been linked to mutations in the VPS13B gene. The main purpose of this study was to determine the genetic cause of CS in an Indian family. Whole exome sequencing (WES) was used to identify the genetic cause of CS in the family. The WES analysis identified a homozygous novel duplication mutation c.5272dupG in the VPS13B gene, leading to formation of a truncating protein. The present study will be advantageous in genetic diagnosis and genetic counseling in CS, and increases the mutational spectrum of this gene.

2.
Am J Trop Med Hyg ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32124721

RESUMO

Micro-RNAs (miRNAs) play a crucial role in immune regulation, and a common miRNA-146a polymorphism (rs2910164) increased the odds of falciparum malaria in pregnant African women. Here, we examined whether this association holds true in a different population, that is, 449 mainly male and adult malaria patients and 666 community controls in southwestern India. Plasmodium vivax malaria (67%) predominated over falciparum malaria (11%) and mixed species infections (22%). Overall, 59% of the study participants carried the miRNA-146a polymorphism. However, it was not associated with the odds of malaria, irrespective of parasite species. This underlines the importance of considering the complexities of clinical manifestations of malaria, genetic background, and parasite species when disentangling the role of human genetic variation, including those of miRNAs in malaria.

3.
Int J Biol Macromol ; 149: 1262-1274, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32044364

RESUMO

Limitation of antibacterial activity, low water vapour, oxygen permeation and mechanical strength are the disadvantages of existing wound dressings. The present research is focused on synthesis of Polyvinyl alcohol (PVA) and Chitosan (CH) hydrogels using freeze thaw process. The formation of AgNPs and PVA/CH hydrogels was confirmed by UV spectroscopy, particle size, morphology, spectral analysis, swelling studies, and in-vitro drug release studies. The particle size of AgNPs was found to be in the range of 20-35 nm with an intense peak at 430 nm. The results of spectral peaks showed that PVA/CH blend maintains characteristics peak of -OH and -NH in the spectrum with higher intensity. The morphology and tensile strength of hydrogels showed a wrinkled surface with an increase in force and extension values from 0.49 to 11.15 N and 45 to 129 mm, respectively. A controlled release of 84.3% (28 h) of Ocimum sanctum extract was noticed from hydrogel discs which scavenges 69.2% of free radicals as compared to raw extract 82.5% (16 h) which scavenges 63.1% of free radicals, respectively. The results of zone of inhibition (ZOI) against gram +ve and gram -ve bacteria was found to be 9.3 mm and 6.3 mm, respectively.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32011565

RESUMO

As beta-thalassemia major patients need regular blood transfusions due to the severe hemoglobin deficiency, the occurrence of related bone defects with simultaneous fluctuations in the biochemical and hematologic parameters is seen. The hospital-based cross-sectional observational study was done to determine and correlate the bone mineral density (BMD) with biochemical parameters and hematologic parameters in 50 regularly transfused beta-thalassemia major patients of older than 6 years of age. Descriptive statistics were analyzed with SPSS version 20.0 software. A P<0.05 was considered as statistically significant. The prevalence of suboptimal BMD at lumbar spine was 86% and at femur neck was 74%. A statistically significant correlation of BMD was found with mean pretransfusion hemoglobin values, serum calcium levels, and serum vitamin D levels (P<0.05). It was concluded that continuous monitoring of the BMD, biochemical, and hematologic parameters in regularly transfused beta-thalassemia major patients may help assess the ongoing deficiencies; helping to maintain timely and regular blood transfusions with supplementation of calcium, vitamin D to ensure good bone health.

5.
Chemosphere ; 248: 126030, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32032876

RESUMO

Gradually increasing concentrations of diclofenac (DCF), a widely used anti-inflammatory drug, in water bodies is an emerging concern because of the persistent characteristics and harmful environmental impact of the drug molecule. In this study, electro-oxidation using a novel copper (Cu) - reduced graphene oxide (rGO) electrode is indicated to be an efficient technology for treating DFC-laden wastewater. The Cu-rGO dispersed carbon film (∼1 mm thickness) is synthesized by carbonization and H2-reduction of a phenolic polymeric film in situ dispersed with a Cu salt and GO. The synthesized self-standing carbon film electrode is used for electro-oxidation of aqueous DCF. Analytical microscopic techniques are used to study the physicochemical properties of the material. Cyclic voltammetry analysis shows the prepared electrode generating a high oxidative current response. Approximately 100% DCF degradation is measured within 1 h at 1 V constant biased potential. Dual roles of Cu-rGO are presented as rGO facilitating direct oxidation via enhanced electron mobility at the electrode surface and Cu nanoparticles (NPs) participating in indirect oxidation by generating OH radicals in aqueous phase. The Cu NPs show an over-potential of -0.5 V vs. Ag/AgCl (100 mM KCl) for oxygen evolution, indicating indirect oxidation of DCF. The high non-faradic current density of 4 mA cm-2 generated at the positive potential (1 V) indicates direct oxidation of DCF. This study clearly indicates electro-oxidation using the Cu-rGO-dispersed carbon film electrode to be an efficient technique for remediation of pharmaceutical pollutants-contaminated wastewater.

6.
Am J Cardiol ; 125(7): 1020-1025, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31973809

RESUMO

Papillary muscles rupture (PMR) is a rare complication of acute myocardial infarction (MI) that can lead to severe hemodynamic compromise, acute heart failure, and death. This study was designed to assess demographics, outcomes, and hospital utilization trends in the management of PMR associated with acute MI. Data were derived from the National Inpatient Sample for the years 2005 to 2014. ICD-9 codes 410.0 to 410.9 were used to identify patients with acute MI. ICD-9 code 429.6 was used to identify patients with PMR. ICD-9 procedures codes 35.23, 35.24, and 35.12 were used to identify patients who underwent mitral valve replacement (MVR) or repair. Of the 3,244,799 admissions, 932 were complicated by PMR (incidence of 0.029%). The majority of patients with PMR were ≥65 years old (60.1%) and male (60.4%). Of those with PMR, 57.5% underwent MVR. Compared to patients without PMR, those with PMR had a significantly higher in-hospital mortality rate (5.3 vs 36.3%, p <0.001), cost of hospitalization ($20,205 vs $74,383, p <0.001) and length of hospital stay (4.67 ± 02 vs 11.2 ± 0.80 days, p <0.001). Predictors of in-hospital mortality in PMR patients were age, inferior wall acute MI, and cardiac arrest. Predictors of MVR in PMR patients were age, female gender, concomitant coronary artery bypass grafting, mechanical circulatory support, longer length of stay, and admission to a large hospital. In conclusion, patients with PMR associated with acute MI have higher risk of in-hospital mortality, greater cost of hospitalization and longer length of stay than patients acute MI without PMR.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31898023

RESUMO

Intense selection for a few desired traits has resulted in reduction of the effective population size (Ne) in most of the plant and livestock populations across the world. The objective of the research was to assess the impact of Ne on the genetic architecture of the population in a simulated data with variable Ne for general population under selection. Along with this, the estimate of Ne and its ratio to adult breeding population (NB) in the census data of small ruminants of India were also investigated. Results indicated that the average inbreeding ([Formula: see text]) decreases with increase in Ne; similarly, increase in [Formula: see text] per generation was highest in population with lowest Ne. Correlation of estimated breeding value (EBV) with true breeding value (TBV) was not much affected with effective population size. An effective number of chromosome segments (Me) in the populations under selection were significantly affected by magnitude of Ne, with linear positive relation between Ne and Me. Results on livestock census data revealed that all the sheep and goat breeds have sufficiently large Ne based on derived and actual census data. The median for ratio of effective population size to adult census size in sheep breeds was 0.120 and for goat breeds was 0.131. Karnah and Poonchi sheep shares the status of endangered breeds due to a smaller number of breeding female population and hence need attention for conservation. The Ne was large in sheep and goat due to less selection pressure as a result of low coverage of breed improvement programs, availability of large number of breeding males, and absence of artificial insemination (AI) in the field flocks. The estimates of Ne and its ratio to the adult census size (NB) excluded several factors such as fluctuating population size and overlapping generations. Study revealed introspection from most of the industrial breeding programs on the issue of Ne for populations under selection. Similarly, in small ruminants, large Ne indicates huge genetic diversity and scope of improvement in the productivity in near future.

8.
Anal Chem ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922725

RESUMO

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay utilizing deuterated natural sulfatide substrate to measure arylsulfatase A (ARSA) activity in leukocytes and dried blood spot (DBS) was developed and validated. These new assays were highly specific and sensitive. Patients with metachromatic leukodystrophy (MLD) and multiple sulfatase deficiency (MSD) demonstrated clear deficit in the enzymatic activity, and can be completely distinguished from normal controls. The leukocyte assay reported here was important for diagnosing MLD and MSD patient and for monitoring the efficacy of therapeutic treatments. On the other hand, ARSA activity was measured in DBS for the first time without an antibody. Currently, this new ARSA DBS assay serves as a second-tier test following sulfatide measurement in DBS for newborn screening of MLD, leading to an elimination of most of the false positives identified by the sulfatide assay. We are also evaluating its potential as the first-tier test for the newborn screening of MLD.

11.
Int J Biol Macromol ; 145: 950-964, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31669274

RESUMO

To overcome the practical limitations of hydrogel preparations, applications and strength-based problems, the present study utilizes the use of sprayers for preparing polyvinyl alcohol/chitosan (PVA/CH) hydrogels. The particle size, morphology, stability, release studies and antibacterial activity of silver nanoparticles (AgNPs) had been studied. The particle size of AgNPs was found to be in the range of 4.59-10 nm (75 °C) with a polydispersity index (PDI) of 0.84. The morphological images exhibited inter-connecting porous structure with pore size in submicron's (<1 µm). Major infra-red spectral peaks of PVA (2946.67 cm-1; stretching of CH, 1142.72 cm-1; CO stretching) and CH (3287.49 cm-1; OH stretching, 2917.48 cm-1; CH stretching) maintain their place in PVA/CH and PVA/CH/Ag hydrogels. In addition, X-ray diffraction (XRD) pattern showed peaks with 2θ values at 38.08°, 44.29° and 64.50° corresponding to the crystal planes of (1 1 1), (2 0 0) and (2 2 0), respectively, allocated to face-centered cubic crystalline structure of AgNPs. The drug release and antibacterial studies showed a maximum release of 91.83% from hydrogels and a concentration dependent zone of inhibition (ZOI) for >24 h, respectively. Thus, the newly developed sprayed hydrogels could turn out to be a suitable dressing material for wound healing applications.

12.
Environ Res ; 181: 108945, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31806288

RESUMO

The review provides a comprehensive overview of the available state-of-the-art of nanoparticles (NPs) and antibiotics (ABs) occurrence and their fate in the natural aquatic settings by addressing different research questions and the challenges faced while addressing those questions. Firstly, understand the interaction of NPs and ABs with themselves in addition to other matrix components (presence of natural organic matter, bacteria, biofilms, other anthropogenic pollutants and metals from natural sources). Secondly, summarize the bactericidal activity of NP and AB due to reactive oxygen species (ROS) production. The complete information was gathered from database and analysed as per the conjectured questions under laboratory versus environmental-relevant conditions (1. Fate of NPs and ABs, and 2. Will the presence of NPs and ABs alone and their mixtures influence the ROS concentration and antibacterial activity), and proposed six reactions to describe the fate of NP and AB in natural aquatic settings. However, laboratory-based studies revealed that NP and AB fate largely depend on the ionic strength, organic matter content and pH of the matrix whereas field based information is missing about this. The former was performed at sterile conditions using sophisticated instruments and standard protocol as compared to latter and can't be replicated under natural aquatic settings due to lack of: (i) accurate environmental concentration of NPs and ABs, (ii) knowledge of bacterial type and their concentration, (iii) optimized protocol and tracking systems. The author's recommendation is to verify the proposed reactions experimentally by using the frequently found pairs of NPs and ABs in the natural aquatic settings. Further, ranked them on their decreasing order of toxicity and informed regulatory bodies for further action. Overall research is needed in the suggested directions to reduce uncertainty behind the impacts of NPs and ABs on the aquatic settings and their role in bactericidal activity.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31776599

RESUMO

Today's world is characterized by increasing population density, human mobility, urbanization, and climate and ecological change. This global dynamic has various effects, including the increased appearance of emerging infectious diseases (EIDs), which pose a growing threat to global health security.Outbreaks of EIDs, like the 2013-2016 Ebola outbreak in West Africa or the current Ebola outbreak in Democratic Republic of the Congo (DRC), have not only put populations in low- and middle-income countries (LMIC) at risk in terms of morbidity and mortality, but they also have had a significant impact on economic growth in affected regions and beyond.The Coalition for Epidemic Preparedness Innovation (CEPI) is an innovative global partnership between public, private, philanthropic, and civil society organizations that was launched as the result of a consensus that a coordinated, international, and intergovernmental plan was needed to develop and deploy new vaccines to prevent future epidemics.CEPI is focusing on supporting candidate vaccines against the World Health Organization (WHO) Blueprint priority pathogens MERS-CoV, Nipah virus, Lassa fever virus, and Rift Valley fever virus, as well as Chikungunya virus, which is on the WHO watch list. The current vaccine portfolio contains a wide variety of technologies, ranging across recombinant viral vectors, nucleic acids, and recombinant proteins. To support and accelerate vaccine development, CEPI will also support science projects related to the development of biological standards and assays, animal models, epidemiological studies, and diagnostics, as well as build capacities for future clinical trials in risk-prone contexts.


Assuntos
Doenças Transmissíveis Emergentes , Epidemias , Vacinas , África Ocidental , Animais , Surtos de Doenças , Alemanha , Humanos
14.
Int J Biol Macromol ; 142: 320-331, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593717

RESUMO

Mycobacterium proteins, especially cell wall associated proteins, interact with host macrophage to regulate the functions and cytokine production. So, identification and characterization of such proteins is essential for understanding tuberculosis pathogenesis. The role of the ABC transporter proteins in the pathophysiology and virulence of Mycobacterium tuberculosis is not clearly understood. In the present study, Rv1273c, an ABC transporter, has been expressed in a non-pathogenic and fast growing Mycobacterium smegmatis strain to explore its role in host pathogen interactions. Over expression of Rv1273c resulted in enhanced intracellular survival in macrophage as well as modified cell wall architecture. We found altered colony morphology and cell surface properties that might be linked with remodelling of bacterial cell wall which may help in the intracellular survival of mycobacterium. However, the enhanced intracellular survival was not found to be the consequence of an increased resistance to intracellular stresses. The activation of macrophage by Rv1273c was associated with perturbed cytokine production. Pharmacological inhibition experiment and western immunoblotting suggested that this altered cytokine profile was mediated possibly by NF-kB and p38 pathway in macrophage. Overall, the present findings indicated that Rv1273c enhanced mycobacterium persistence and mediated the evasion of immune responses during infection.

15.
J Artif Organs ; 23(1): 47-53, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31571018

RESUMO

A new polymeric adsorbent to improve portable dialysis treatment by simplifying urea removal at the dialysate regeneration step is proposed. An adsorbent to remove urea was synthesized by molecular imprinting technology that can potentially overcome drawbacks existing in urease enzyme-based dialysate regeneration technology. Molecularly imprinted polymer (MIP) for urea generates cavities both in shape and in size targeted for urea. Using the synthesized MIP, we have shown removal of urea present in the dialysate buffer. Various experimental conditions such as choice of monomers, porogen, and template to monomer ratios were optimized to achieve highest binding capacity on a column flow through system monitored using high-performance liquid chromatography (HPLC). Taking advantage of the basicity of urea molecule, monomers having Brønsted acidic groups such as acrylic acid, methacrylic acid and itaconic acid were screened. The MIP synthesized using urea:acrylic acid:EGDMA (1:4:12) in acetonitrile:ethylene dichloride (1:1) as porogen gave highest binding capacity of 24.5 g/kg of urea in the dialysate buffer matrix.

17.
Angew Chem Int Ed Engl ; 59(7): 2881-2889, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31825552

RESUMO

Five-fold intertwined Agx Ni1-x (x=0.01-0.25) heterogeneous alloy nanocrystal (NC) catalysts, prepared through unique reagent combinations, are presented. With only ca. 5 at % Ag (AgNi-5), Pt-like activity has been achieved at pH 14. To reach a current density of 10 mA cm-2 the extremely stable AgNi-5 requires an overpotential of 24.0±1.2 mV as compared to 20.1±0.8 mV for 20 % Pt/C, both with equal catalyst loading of 1.32 mg cm-2 . The turnover frequency (TOF) is as high as 2.1 H2  s-1 at 50 mV (vs. RHE). Site-specific elemental analyses show the Ag:Ni compositional variation, where the apex and edges of the decahedra are Ag-rich, thereby exposing Ni onto the faces to achieve maximum charge transport for an exceptional pH universal HER activity. DFT calculations elucidate the relative H-atom adsorption capability of the Ni centers as a function of their proximity to Ag atom.

18.
J Pediatr ; 216: 204-207, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31732130

RESUMO

OBJECTIVE: To test, in a newborn screening (NBS) laboratory, the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assay 5 enzymatic activities in dried blood spots (DBS) for NBS of 5 lysosomal storage diseases (mucopolysaccharidosis [MPS]-II, MPS-IIIB, MPS-IVA, MPS-VI, and MPS-VII). STUDY DESIGN: Three mm punches from de-identified DBS were obtained from the Washington NBS laboratory and submitted to the 5-plex LC-MS/MS assay. Screen cut-offs were established by analyzing the enzymatic activity in patients confirmed to have the MPS disorder. DNA sequencing of the relevant gene was performed on a second DBS punch for all samples with enzyme activity below 10% of the mean daily activity. RESULTS: (1) For MPS-II, 18 below cut-off samples, 1 pathogenic genotype, and 2 "high risk" genotypes; (2) For MPS-IIIB, no below cut-off samples; (3) For MPS-IVA, 8 below cut-off samples, 4 non-pathogenic genotypes, 4 genotypes unobtainable; (4) For MPS-VI, 4 below cut-off samples and no high-risk genotypes; (5) For MPS-VII, 1 below cut-off sample confirmed by genotype and clinical report to be affected. CONCLUSIONS: These results establish that the number of initial screen positive samples is low and manageable. Thus, population newborn screening for these conditions is feasible in a state newborn screening laboratory.

19.
Chemosphere ; 243: 125239, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31733544

RESUMO

An extensive application and potential release of nanoparticles (NPs) through wastewater treatment plants to agricultural lands have created an urgent necessity to evaluate food safety. The study here grew Spinacia oleracea until maturity in the soil and irrigated with CuO and ZnO NPs (as single and as a binary mixture). The plants were grown in soil containing pots and were exposed to NPs (CuO and ZnO) and ions (Cu2+ and Zn2+) (concentration = 1.2 × 10-4, 1.2 × 10-3, 1.2 × 10-2 mol/Kg of soil); a binary mixture (CuO + ZnO and Cu2++Zn2+) concentration = 1.2 × 10-4+1.2 × 10-4 mol/Kg of soil, respectively. At maturity, plant fresh weight, root length, and elemental content (Cu and Zn) were quantified. Results showed significant adverse effects on plant biomass exposed at 1.2 × 10-2 mol/Kg of soil (percentage reduction = 36%, 26% and 45% for CuO, ZnO, and CuO + ZnO NPs, respectively). The interaction of toxicity between two NPs and ions on reduction in fresh weight was observed to be additive. Desorption studies were performed for determining root-surface adsorbed CuO and ZnO NPs using three different concentrations of Na4EDTA. The estimated internal uptake of Cu and Zn was found to be 0.4 mg Cu/g dry weight and 0.7 mg Zn/g dry weight in the shoot portion of the plant and 3.06 mg Cu/g dry weight and 3.4 mg Zn/g dry weight in the root portion of the plant, respectively. (at 1.2 × 10-2 mol/Kg of soil). Exposure of metal ions has shown a higher reduction in biomass and higher uptake in plants as compared to NPs. The projected hazard quotient values for the intake of NPs by children was found to be greater than 1 indicating risks to children. Given the importance of food safety, determination of the potential risk of consuming contaminated plants, irrigated using nanoparticles containing wastewater is advised.

20.
J Biomol Struct Dyn ; 38(4): 1083-1093, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30898047

RESUMO

Protein-protein interactions are crucial for all biological processes. Compiling this network provides many new insights into protein function and gives directions for the development of new drugs targeted to the pathogen. Mycobacterium tuberculosis Nucleoside diphosphate kinase (Mtb Ndk) has been reported to promote survival of mycobacterium within the macrophage and contribute significantly to mycobacterium virulence. Hence, the present study was aimed to identify and characterize the interacting partner for Ndk. The in vitro experiments, pull down and far western blotting have demonstrated that Mtb Ndk interacts with Rv1273c, a probable drug ABC transporter ATP-binding protein annotated to export drugs across the membrane. This observation was further confirmed by molecular docking and dynamic simulations studies. The homology model of Rv1273c was constructed and docked with Mtb Ndk for protein-protein interaction analysis. The critical residues involved at interface of Rv1273c-Ndk interaction were identified. MDS and Principal Component analysis carried out for conformational feasibility and stability concluded that the complex between the two proteins is more stable as compared to apo proteins. Our findings would be expected to improve the dissection of protein-protein interaction network and significantly advance our understanding of tuberculosis infection.Communicated by Ramaswamy H. Sarma.

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