With an increased demand for rapid, diagnostic tools for TB and drug resistance detection, Truenat
MTB-RIF assay has proven to be a rapid point of care molecular test. The present study aimed to ...establish a proof of concept of using Trueprep-extracted DNA for line-probe assay (LPA) testing.
A total of 150 sputum samples (MTB-positive at Truenat sites) were divided into two aliquots. One aliquot was used for DNA extraction using the Trueprep device and MTB testing. The second aliquot of the sample was subjected to GenoLyse
DNA extraction. DNA from both the Trueprep and GenoLyse methods was subjected to first-line (FL) and second-line (SL) LPA testing.
Of 139 Trueprep-extracted DNA, respectively 135 (97%) and 105 (75%) had interpretable results by FL and SL-LPA testing. Of 128 GenoLyse-extracted DNA, all 128 (100%) had interpretable FL-LPA results and 114 (89%) had interpretable SL-LPA results.
The results obtained in this study indicate that Trueprep-extracted DNA can be used in obtaining valid LPA results. However, the study needs to be conducted on a larger sample size before our recommendations can be used for policy-making decisions.
The p66ShcA protein controls cellular responses to oxidative stress, senescence, and apoptosis. Here, we test the hypothesis that aging phenotype(s) commonly associated with the broad category of ...chronic kidney disease are accelerated in diabetic kidneys and linked to the p66ShcA locus. At the organ level, tissue stem cells antagonize senescent phenotypes by replacing old dysfunctional cells. Using established methods, we isolated a highly purified population of stem cell antigen-1-positive mesenchymal stem cells (Sca-1
MSCs) from kidneys of wild-type (WT) and p66 knockout (p66 KO) mice. Cells were plated in culture medium containing normal glucose (NG) or high glucose (HG). Reactive oxygen species (ROS) metabolism was substantially increased in WT MSCs in HG medium in association with increased cell death by apoptosis and acquisition of the senescent phenotype. DNA microarray analysis detected striking differences in the expression profiles of WT and p66 KO-MSCs in HG medium. Unexpectedly, the analysis for p66 KO-MSCs revealed upregulation of Wnt genes implicated in self-renewal and differentiation. To test the in vivo consequences of constitutive p66 expression in diabetic kidneys, we crossed the Akita diabetic mouse with the p66KO mouse. Homozygous mutation at the p66 locus delays or prevents aging phenotype(s) in the kidney that may be precursors to diabetic nephropathy.
In most developing countries, sputum smear microscopy for acid-fast bacilli remains the front line and often the only diagnostic tool for the diagnosis of tuberculosis (TB), making quality assurance ...of smear microscopy an important activity.
To evaluate the results of a pilot study, where the random blinded rechecking for the entire state of Delhi was conducted at a reference laboratory.
Slides from 25 Revised National Tuberculosis Control Programme designated districts (200 peripheral microscopy centres) in Delhi were re-read after proper coding by all the Senior Tuberculosis Laboratory Supervisors (STLS) at an intermediate reference laboratory under proper supervision.
Of 12,162 re-read slides, 204 discrepant results were found. Of these, 150 (73.5%) errors were attributed to the peripheral microscopy centres and 54 (26.5%) to STLS. High false-positive errors were observed at a frequency of 12/150 (8%), and high false-negative errors at a frequency of 38/150 (25%). Minor errors, i.e., low false-negative, low false-positive and quantification errors, were observed at frequencies of respectively 68/150 (45.3%), 17/150 (11.3%) and 15/150 (10.0%).
Greater stringency in the supervision of random blinded rechecking at the district level is essential to make smear rechecking more efficient and effective.
Fenofibrate, a well-known normolipidemic drug, has been shown to exert strong anticancer effects against tumors of neuroectodermal origin including glioblastoma. Although some pharmacokinetic studies ...were performed in the past, data are still needed about the detailed subcellular and tissue distribution of fenofibrate (FF) and its active metabolite, fenofibric acid (FA), especially in respect to the treatment of intracranial tumors. We used high performance liquid chromatography (HPLC) to elucidate the intracellular, tissue and body fluid distribution of FF and FA after oral administration of the drug to mice bearing intracranial glioblastoma. Following the treatment, FF was quickly cleaved to FA by blood esterases and FA was detected in the blood, urine, liver, kidney, spleen and lungs. We have also detected small amounts of FA in the brains of two out of six mice, but not in the brain tumor tissue. The lack of FF and FA in the intracranial tumors prompted us to develop a new method for intracranial delivery of FF. We have prepared and tested in vitro biodegradable poly-lactic-co-glycolic acid (PLGA) polymer wafers containing FF, which could ultimately be inserted into the brain cavity following resection of the brain tumor. HPLC-based analysis demonstrated a slow and constant diffusion of FF from the wafer, and the released FF abolished clonogenic growth of glioblastoma cells. On the intracellular level, FF and FA were both present in the cytosolic fraction. Surprisingly, we also detected FF, but not FA in the cell membrane fraction. Electron paramagnetic resonance spectroscopy applied to spin-labeled phospholipid model-membranes revealed broadening of lipid phase transitions and decrease of membrane polarity induced by fenofibrate. Our results indicate that the membrane-bound FF could contribute to its exceptional anticancer potential in comparison to other lipid-lowering drugs, and advocate for intracranial delivery of FF in the combined pharmacotherapy against glioblastoma.
Indian Earth Observation Satellite Cartosat-1 data were evaluated for the estimation of biophysical variables, including as tree height, crown diameter, canopy density and canopy gap, that are ...crucial for the estimation of stand volume, biomass and generation of site index (an indicator of site quality of growing stock). Investigations were carried out at a site covering the major dominant forest species grown in India. Cartosat-1 stereo data were analysed in conjunction with differential global positioning system (DGPS) measurements to generate a digital elevation model (DEM) and an orthoimage, which were used to estimate the biophysical variables. Analysis using grey-level co-occurrence texture measures was performed for separation of forest species, homogeneity of the classes of forest stands, stratification and measurement of crown area, canopy gap and stand density. Field measurements of tree height, diameter at breast height (DBH), stand density, age and crown diameter were conducted for each stand. Empirical models for the estimation of DBH were developed and validated with Cartosat-1-derived height and crown diameter. Measured and estimated values were found to be in close proximity to each other. A local contrast co-occurrence measure (contrast, mean and variance) was suitable for the estimation of average crown diameter, stand density and canopy gap area for each forest stand class. The texture image provided information on structural attributes (i.e. stand density, crown diameter and canopy gap of the forest tree stands). The results presented in this study show that the Cartosat-1-derived DEM and orthoimage have potential for the estimation of stem volume, growing stock conditions, and biomass and site index for important timber species.
Luteal dysfunction in pregnant women is associated with early pregnancy loss, making the study of structure and function of the corpus luteum (CL) critical. Luteinizing hormone (LH) plays a crucial ...role in the mammalian female reproduction majorly by regulating luteal development. In rats, the luteotropic roles of LH have been widely investigated but its role in the process of luteolysis has received little attention. In this study, we explored the luteolytic actions of LH during different stages of pregnancy in rats. Repeated administration of LH during the late and mid-stages of pregnancy led to functional luteolysis during both stages, while structural luteolysis was observed only during the late-stage. We analyzed the involvement of cAMP/PKA/CREB pathway, MAP kinases and β-arrestins to elucidate the molecular mechanism of LH-mediated luteolysis. The results indicate that the repeated administration of LH causes LH/CGR desensitization along with an increase in β-arrestin 1 expression, while luteal expression of MAP kinases remained unaffected. Further, siRNA-mediated depletion of β-arrestin 1 in primary luteal-cell cultures prevents initiation of the luteolysis process to some extent during both the stages of pregnancy, underscoring its role in LH mediated-luteolysis. In conclusion, the luteolytic actions of LH appear to involve more than one signaling pathway and cAMP/PKA/CREB pathway appears to be the key regulator. This is the first report to show a positive correlation between β-arrestin 1 and 20α-hsd expression. These findings have implications for our understanding of the molecular pathways that regulate luteolysis.
Cisplatin-based metallodrugs are traditionally utilized as anticancer agents. Nonetheless, these drugs have adverse effects on normal tissues since cisplatin eliminates the body amid cancerous growth ...cells by destroying the sequence of genomic DNA. As a result, the metallodrug structure demonstrated numerous antagonistic behaviours to the malignant tumour development system associated with nucleic acid G-quadruplex. This paper systematically explored the development of successful procedures and competent anticancer drugs that expressly collaborate, resolve, or divide G4 structures. In the therapeutic domain, we highlighted the cutting-edge G4-metallo-structures, their interface mechanisms, and the potential for use as anticancer medicines. Furthermore, this paper also describes the methodologies utilized to discriminate the binding capacity between G-quadruplex and metallo-structures. This review will help to create metallodrugs from the most significant electrical supplementary design specification to a progressively logical bio-science level.
Cu(I) 4H‐imidazolate complexes are rare examples of Cu(I) complexes with chelating anionic ligands and are potent photosensitizers with unique absorption and photoredox properties. In this ...contribution, five novel heteroleptic Cu(I) complexes with monodentate triphenylphosphine co‐ligands are investigated. As a consequence of the anionic 4H‐imidazolate ligand and in contrast to comparable complexes with neutral ligands, these complexes are more stable than their homoleptic bis(4H‐imidazolato)Cu(I) congeners. Here, the ligand exchange reactivity was studied by 31P‐,19F‐, and variable temperature NMR and the ground state structural and electronic properties by X‐ray diffraction, absorption spectroscopy, and cyclic voltammetry. The excited‐state dynamics were investigated by femto‐ and nanosecond transient absorption spectroscopy. The observed differences, with respect to chelating bisphosphine bearing congeners, are often due to the increased geometric flexibility of the triphenylphosphines. These observations render the investigated complexes interesting candidates for photo(redox)reactions not accessible with chelating bisphosphine ligands.
Hop on hop off: Typically, heteroleptic Cu(I)DiiminePPh3 complexes tend to form the homoleptic counterpart. But this is not observed when the diimine is an anionic 4H‐imidazolate. Despite dynamic PPh3 ligand exchange in solution the deeply colored, photoredox‐active Cu(I)4H‐imidazolatoPPh3 complexes are stable.
Soft matter integration of photosensitizers and catalysts provides promising solutions to developing sustainable materials for energy conversion. Particularly, hydrogels bring unique benefits, such ...as spatial control and 3D‐accessibility of molecular units, as well as recyclability. Herein, the preparation of polyampholyte hydrogels based on poly(dehydroalanine) (PDha) is reported. Chemically crosslinked PDha with bis‐epoxy poly(ethylene glycol) leads to a transparent, self‐supporting hydrogel. Due to the ionizable groups on PDha, this 3D polymeric matrix can be anionic, cationic, or zwitterionic depending on the pH value, and its high density of dynamic charges has a potential for electrostatic attachment of charged molecules. The integration of the cationic molecular photosensitizer Ru(bpy)32+ (bpy = 2,2′‐bipyridine) is realized, which is a reversible process controlled by pH, leading to light harvesting hydrogels. They are further combined with either a thiomolybdate catalyst (Mo3S132−) for hydrogen evolution reaction (HER) or a cobalt polyoxometalate catalyst (Co4POM = Co4(H2O)2(PW9O34)210−) for oxygen evolution reaction (OER). Under the optimized condition, the resulting hydrogels show catalytic activity in both cases upon visible light irradiation. In the case of OER, higher photosensitizer stability is observed compared to homogeneous systems, as the polymer environment seems to influence decomposition pathways.
Chemical‐crosslinking of polydehydroalanine leading to a polyampholyte hydrogel with a high density of charges and adjustable net charge is reported. This allows for reversible immobilization of charged molecular photosensitizers (PS) and catalysts (CAT), resulting in catalytically active hybrid materials. Herein, they use this for both hydrogen evolution and water oxidation catalysis (WO).
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