Temperature gradient focusing of bio-analyte in a microfluidic channel dealing with non-Newtonian electrolyte considering temperature-dependent zeta potential.

Temperature gradient focusing (TGF) relies on establishing a precise balance between the electrophoretic motility of a target analyte and the advective flow of the background electrolyte (BGE) to locally concentrate the analyte in a microfluidic configuration. This paper presents a finite-element-based numerical analysis where the coupled electric field and the transport equations are solved to describe the effects of the shear-dependent apparent viscosity of a non-Newtonian BGE on the localized concentration buildup of a charged bio-sample inside a microchannel by TGF via Joule heating. Effects of the temperature-dependent nature of the wall zeta potential and the flow behavior index (n) of BGE on the flow, thermal, and species concentration profiles inside the microchannel have been investigated. Study using a fluorescein-Na analyte sample shows that the maximum normalized analyte concentration (Cmax /C0 ) reduces as the zeta potential increases linearly with temperature. The maximum concentration enhancement is achieved when the BGE displays the Newtonian rheology. For example, Cmax /C0 increases 134- to 280-fold when n is increased from 0.8 to 1 (pseudoplastic regime) and again reduces to 190-fold when n increases further from 1 to 1.2 (dilatant regime).

Kaempferol with Verapamil impeded panoramic chemoevasion pathways in breast cancer through ROS overproduction and disruption of lysosomal biogenesis.

BACKGROUND: Reactive oxygen species (ROS) at low level promotes cell survival through lysosome induced autophagy induction. Glucose stress induced acidosis, hypoxia, ROS, upregulates markers related to cancer stemness and multidrug resistance. Also, lysosomal upregulation is proposed to be one of the important indicators of cell survival under ROS induced stress. Studies supported that, stimulation of Lysosome-TFEB-Ca2+ cascade has important role in induction of chemoresistance and survival of cancerous cells. PURPOSE: To observe the effect of synergistic drug combination, Kaempferol and Verapamil on markers regulating chemoevasion, tumor stemness & acidosis as well as lysosome upregulation pathways, under low as well as high glucose conditions. HYPOTHESIS: Based on our earlier observation as well as previous reports, we hypothesized, our drug combination Kaempferol with Verapamil could attenuate markers related to chemoevasion, tumor stemness & acidosis as well as lysosome-TFEB-Ca2+ pathway, all of which have indispensable association and role in chemoresistance. METHODS: RNA and protein expression of candidate genes, along with ROS production and Ca2+ concentrations were measured in ex vivo models in altered glucose conditions upon treatment with KV. Also, computational approaches were utilized to hypothesize the mechanism of action of the drug combination. PCR, IHC, western blotting and molecular docking approaches were used in this study. RESULTS: The overproduction of ROS by our candidate drugs KV, downregulated the chemoresistance and tumor acidosis markers along with ATP1B1 and resulted in lysosomal disruption with reduction of Ca2+ release, diminishing TFEB expression under low glucose condition. An anomalous outcome was observed in high glucose conditions. We also observed KV promoted the overproduction of ROS levels thereby inducing autophagy-mediated cell death through the upregulation of LC3-II and p62 in low glucose conditions. The ex vivo studies also corroborate with in silico study that exhibited the parallel outcome. CONCLUSION: Our ex-vivo and in-silico studies revealed that our candidate drug combination KV, could effectively target several pathways regulating chemoresistance, that were not hitherto studied in the same experimental setup and thus may be endorsed for therapeutic purposes.

Satellite hyperspectral imaging technology as a potential rapid pollution assessment tool for urban landfill sites: case study of Ghazipur and Okhla landfill sites in Delhi, India.

Hyperspectral imaging technology has been used for biochemical analysis of Earth's surface exploiting the spectral reflectance signatures of various materials. The new-generation Italian PRISMA (PRecursore IperSpettrale dellaMissione Applicativa) hyperspectral satellite launched by the Italian space agency (ASI) provides a unique opportunity to map various materials through spectral signature analysis for recourse management and sustainable development. In this study PRISMA hyperspectral satellite imagery-based multiple spectral indices were generated for rapid pollution assessment at Ghazipur and Okhla landfill sites in Delhi, India. It was found that the combined risk score for Okhla landfill site was higher than the Ghazipur landfill site. Various manmade materials identified, exploiting the hyperspectral imagery and spectral signature libraries, indicated presence of highly saline water, plastic (black, ABS, pipe, netting, etc.), asphalt tar, black tar paper, kerogen BK-Cornell, black paint and graphite, chalcocite minerals, etc. in large quantities in both the landfill sites. The methodology provides a rapid pollution assessment tool for municipal landfill sites.

Esophageal Intramural Haematoma related Dysphagia: A rare complication after thrombolysis.

Esophageal Intramural Haematoma (EIH) is a rare entity usually caused by repeated emesis or trauma. It is diagnosed on the basis of upper gastrointestinal endoscopy and radiology. Treatment is conservative unless hemodynamic instability prevails. Use of anticoagulation or thrombolytic therapy is believed to be a risk factor rather than a causative etiology. However, a review of literature shows only few cases occurring post-thrombolysis. We report about a patient of myocardial infarction who was thrombolyzed with streptokinase. He developed hematemesis and dysphagia a few hours after thrombolysis despite ECG resolution of his ST elevation. He was diagnosed to have EIH on basis of endoscopic and computed tomographic findings. His symptoms improved within two weeks, and a repeat UGIE showed resolution of the hematoma.

Kaempferol attenuates viability of ex-vivo cultured post-NACT breast tumor explants through downregulation of p53 induced stemness, inflammation and apoptosis evasion pathways.

Early onset of chemotherapy evasion is a therapeutic challenge. Chemotherapy-induced upregulation of stem cell markers imparts invasiveness and metastatic property to the resident tumor. The efficacy of Kaempferol in attenuating epithelial to mesenchymal transition has earlier been established in the breast cancer cell. In our study population, progression-free survival was observed to be statistically more significant in post-NACT low-grade tumors than the high-grade tumors. Further, in post-NACT TNBCs, high-grade tumors showed a preponderance of strong nuclear p53 expression and very low expression of Caspase 3, indicating that, altered p53 expression predisposes these tumors to apoptosis escape and up-regulation of stemness markers. Herein, we report the robust efficacy of Kaempferol on ex-vivo grown breast tumors, derived from post-NACT TNBC patients, through downregulation of nuclear p53, CD44, ALDH1, NANOG, MDR1, Ki67, BCL2 and upregulation of Caspase 3. Such tumors also showed concurrent deregulated RNA and protein expression of CD44, NANOG, ALDH1 and MDR1 with upregulation of Caspase 3 and cleaved Caspase 3, upon Kaempferol treatment. Validation of efficacy of the treatment dosage of Kaempferol through immunophenotyping on MDA-MB-231, suggested that Kaempferol at its IC-50 dosage was effective against CD44 and CD326 positive breast cancer through deregulating their expression. Protein-protein interaction network through STRING pathway analysis and co-expression study of candidate proteins showed the highest degree of co-expression of p53 and KI-67, CD44, NF- kappaB, ALDH1, NANOG, MDR1, and BCL2. Thus, potentially targetable oncogenic protein markers, that are susceptible to downregulation by Kaempferol, provides insight into biomarker-driven therapeutic approaches with it.

Serial measurements of faecal calprotectin may discriminate intestinal tuberculosis and Crohn's disease in patients started on antitubercular therapy.

BACKGROUND: Response to antitubercular therapy (ATT) is often used to differentiate intestinal tuberculosis (ITB) from Crohn's disease. Role of non-invasive biomarkers to predict mucosal response to ATT is unclear. MATERIALS AND METHODS: A prospective study to compare faecal calprotectin and serum C-reactive protein (CRP) levels at diagnosis, 2 and 6 months of ATT in patients with suspected ITB started on ATT was done. The patients were eventually divided into two groups: ITB or alternative diagnosis (OTH). Decline of calprotectin and CRP levels was used to compute area under the receiver operating characteristic (AUROC) to predict mucosal healing at 2 months. RESULTS: Thirty-seven patients (mean age: 34.95 ± 16.35 years, 23 males) were included and 28 (75.67%) were diagnosed as ITB while nine (24.32%) had alternative diagnosis (OTH). The median faecal calprotectin values of ITB and OTH groups at baseline, 2 months and 6 months were 216 and 282 µg/g (P = 0.466), 43 and 216 µg/g (P = 0.003), and 26 and 213 µg/g (P < 0.001), respectively. The median CRP values at baseline, 2 months and 6 months were 18 and 30 mg/L (P = 0.767), 4.7 and 15 mg/L (P = 0.025), and 3 and 10.85 mg/L (P = 0.068), respectively. The AUROC of percent decline in faecal calprotectin and serum CRP at 2 months for mucosal healing were 0.8287 [95% confidence inteval (CI) 0.6472-1] and 0.6018 (95% CI 0.4079-0.7957), respectively. CONCLUSION: Faecal calprotectin can help in assessing response to therapy in suspected ITB patients started on empirical ATT.

Symptomatic myositis ossificans following computer navigated total knee replacement: a complication of fixed femoral marker placement.

Myositis ossificans is a rare cause of pain following knee arthroplasty. We describe a 72-year-old woman who developed symptomatic early onset myositis ossificans at the femoral marker pin site following navigated knee arthroplasty.

Oxygen binding to sulfur in nitrosylated iron--thiolate complexes: relevance to the Fe-containing nitrile hydratases.

Iron-nitrosyl complex containing S-bonded monosulfinate [PPN][(NO)Fe(S,SO2-C6H4)(S,S-C6H4)] (3) has been isolated from sulfur oxygenation of complex [PPN][(NO)Fe(S,S-C6H4)2] (2) which is obtained from addition of NO molecule to [PPN][(C4H8O)Fe(S,S-C6H4)2] (1) in organic solvents. This result reveals that binding of NO to the iron center promotes sulfur oxygenation of iron dithiolates by dioxygen and stabilizes the S-bonded sulfinate iron species. Analysis of the bond angles for complexes 2 and 3 reveals that iron is best described as existing in a distorted trigonal bipyramidal coordination environment surrounded by one NO, three thiolates, and one sulfinate in complex 3, whereas the distorted square pyramidal geometry is adopted in complex 2. Complex 3 further reacts in organic solvents with molecular oxygen in the presence of [PPN][NO2] to produce the dinuclear bis(sulfinate) complex [PPN]2[(NO)Fe(SO2,SO2-C6H4)(S,S-C6H4)]2 (4). Complex 3 showed reaction with PPh3 in THF/CH2Cl2 to yield complex 2 and Ph3PO. Upon photolysis of CH2Cl2 solution of complex 3 under N2 purge at ambient temperature, the UV-vis and IR spectra consistent with the formation of complex 2 demonstrate that complex 2 and 3 are photochemically interconvertible. Obviously, complex 3 is thermally quite stable but is photochemically active toward [O] release. Also described are the X-ray crystal structures of 3 and 4.

Giant cell tumour of the patellar tendon sheath--an unusual cause of anterior knee pain: a case report.

We present a case of a giant cell tumour of the patellar tendon sheath with anterior knee pain. The relevant MRI findings and differential diagnosis of such lesions is discussed here.