Pediatric Critical Care Referrals for Tertiary Inpatient and Transport Services in Canada's Maritime Provinces: A Retrospective Cohort Study.

OBJECTIVE: Accurate triage of children referred for tertiary pediatric critical care services is crucial to ensure optimal disposition and resource conservation. We aimed to explore the characteristics and level of care needs of children referred to tertiary pediatric critical care inpatient and transport services and the characteristics of referring physicians and hospitals to which these children present. METHODS: We conducted a 1-year retrospective cohort study of children (< 16 years) with documented referral to pediatric critical care and specialized transport services at a tertiary pediatric hospital from regional (24/7 pediatrician on-call coverage) and community (no pediatric specialty services) hospitals in Canada's Maritime provinces. RESULTS: We identified 205 documented referrals resulting in 183 (89%) transfers; 97 (53%) were admitted to the pediatric intensive care unit (PICU). Of 150 children transferred from centers with 24/7 pediatric specialist coverage, 45 (30%) were admitted to the tertiary hospital pediatric medical unit with no subsequent admission to the PICU. Of 20 children transferred from community hospitals and admitted to the tertiary hospital general pediatric medical unit, 9 (45%) bypassed proximate regional hospitals with specialist pediatric care capacity. The specialized pediatric critical care transport team performed 151 (83%) of 183 interfacility transfers; 83 (55%) were admitted to the PICU. CONCLUSION: One third of the children accepted for interfacility transfer after pediatric critical care referral were triaged to a similar level of care as could be provided at the sending or nearest regional hospital. Improved utilization of pediatric expertise in regional hospitals may reduce unnecessary pediatric transports and conserve valuable health care resources.

Introduction of a ß-leucine residue instead of leucine9 and glycine10 residues in Temporin L for improved cell selectivity, stability and activity against planktonic and biofilm of methicillin resistant S. aureus.

Leucine and glycine residues, at the 9th and 10th positions of helical domain of naturally occurring antimicrobial peptide (AMP), Temporin L were substituted with an unnatural amino acid, ß-leucine (homovaline) to improve its serum protease stability, haemolytic/cytotoxic properties and reduce the size to some extent. The designed analogue, L9ßl-TL showed either equal or improved antimicrobial activity to TL against different microorganisms including the resistant strains. Interestingly, L9ßl-TL also exhibited lower haemolytic and cytotoxic activities against human red blood cells and 3T3 cells, respectively. Moreover, L9ßl-TL showed antibacterial activity in presence of 25% (v/v) human serum and showed resistance against proteolytic cleavage in presence of it that suggested the serum protease stability of the TL-analogue. L9ßl-TL exhibited un-ordered secondary structures in both bacterial and mammalian membrane mimetic lipid vesicles as compared to the helical structures of TL in these environments. However, tryptophan fluorescence studies demonstrated more selective interaction of L9ßl-TL with bacterial membrane mimetic lipid vesicles in comparison to non-selective interactions of TL with both kinds of lipid vesicles. Membrane depolarization studies with live MRSA and bacterial membrane-mimetic lipid vesicles suggested a membrane-disrupting mode of action of L9ßl-TL. L9ßl-TL showed faster bactericidal mechanism compared to TL against MRSA. Interestingly, L9ßl-TL was found as more potent than TL either in inhibiting biofilm formation or in eradicating the mature biofilm formed by MRSA. Overall, the present work demonstrates a simple and useful strategy to design of an analogue of TL, with minimal modifications while maintaining its antimicrobial activity with lesser toxicity and higher stability which could be attempted for other AMPs as well.

Intense green light emission and thermoluminescence glow curve analysis of Tb3+ -activated CaY2 O4 phosphor.

Here, the synthesis and luminescence analysis of the Tb3+ -activated phosphor were reported. The CaY2 O4 phosphors were synthesized using a modified solid-state reaction method with a variable doping concentration of Tb3+ ion (0.1-2.5 mol%). As synthesized, the phosphor was characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction analysis techniques for the optimized concentration of doping ions. The prepared phosphor showed a cubic structure, and FTIR analysis confirmed functional group analysis. It was discovered that the intensity of 1.5 mol% was higher than at other concentrations after the photoluminescence (PL) excitation and emission spectra were recorded for different concentrations of doping ions. The excitation was monitored at 542 nm, and the emission was monitored at 237 nm. At 237 nm excitation, the emission peaks were found at 620 nm (5 D4 →7 F3 ), 582 nm (5 D4 →7 F4 ), 542 nm (5 D4 →7 F5 ), and 484 nm (5 D4 →7 F6 ). The 1931 CIE (x, y) chromaticity coordinates showed the distribution of the spectral region calculated from the PL emission spectra. The values of (x = 0.34 and y = 0.60) were very close to dark green emission. Therefore, the produced phosphor would be very useful for light-emitting diode (green component) applications. Thermoluminescence glow curve analysis for various concentrations of doping ions and various ultraviolet (UV) exposure times was carried out, and a single broad peak was found at 252°C. The computerized glow curve deconvolution method was used to obtain the related kinetic parameters. The prepared phosphor exhibited an excellent response to UV dose and could be useful for UV ray dosimetry.

Control Release of Adenosine Potentiate Osteogenic Differentiation within a Bone Integrative EGCG-g-NOCC/Collagen Composite Scaffold toward Guided Bone Regeneration in a Critical-Sized Calvarial Defect.

The regeneration of critical-sized bone defects with biomimetic scaffolds remains clinically challenging due to avascular necrosis, chronic inflammation, and altered osteogenic activity. Two confounding mechanisms, efficacy manipulation, and temporal regulation dictate the scaffold's bone regenerative ability. Equally critical is the priming of the mesenchymal stromal cells (MSCs) toward lineage-specific differentiation into bone-forming osteoblast, which particularly depends on varied mechanochemical and biological cues during bone tissue regeneration. This study sought to design and develop an optimized osteogenic scaffold, adenosine/epigallocatechin gallate-N,O-carboxymethyl chitosan/collagen type I (AD/EGCG-g-NOCC@clgn I), having osteoinductive components toward swift bone regeneration in a calvarial defect BALB/c mice model. The ex vivo findings distinctly establish the pro-osteogenic potential of adenosine and EGCG, stimulating MSCs toward osteoblast differentiation with significantly increased expression of alkaline phosphatase, calcium deposits, and enhanced osteocalcin expression. Moreover, the 3D matrix recapitulates extracellular matrix (ECM) properties, provides a favorable microenvironment, structural support against mechanical stress, and acts as a reservoir for sustained release of osteoinductive molecules for cell differentiation, proliferation, and migration during matrix osteointegration observed. Evidence from in vivo experiments, micro-CT analyses, histology, and histomorphometry signify accelerated osteogenesis both qualitatively and quantitatively: effectual bone union with enhanced bone formation and new ossified tissue in 4 mm sized defects. Our results suggest that the optimized scaffold serves as an adjuvant to guide bone tissue regeneration in critical-sized calvarial defects with promising therapeutic efficacy.

Characterisation of cholinesterases in mucous secretions and their localisation in epidermis of Labeo rohita and Cirrhinus mrigala.

Cholinesterases are multifunctional enzymes and have been associated with diverse physiological functions in addition to their classical role at synapses. In the present study, cholinesterase (ChE) isozymes have been characterised in mucous secretions and their activity has been localised in the epidermis of Labeo rohita and Cirrhinus mrigala. Zymography using specific substrates and inhibitors revealed the presence of two ChE isozymes-ChE-1 and ChE-2. The isozyme ChE-1 was characterised as an atypical butyrylcholinesterase and ChE-2 as a typical acetylcholinesterase in skin mucous secretions of both the fish species. Enzyme histochemical analysis demonstrated the presence of ChE activity in the epidermis of the fish species investigated. In both the fish species, strong ChE activity was observed in the outer-layer epithelial cells, taste buds and neuromasts. The middle and basal layer epithelial cells showed moderate to weak ChE activity. Club cells and mucous goblet cells showed the absence of ChE activity. Characterisation with specific inhibitors indicates that acetylcholinesterase (AChE) was the major cholinesterase type expressed in the epidermis of the two fish species investigated. Immunohistochemical localisation of apoptotic and cell proliferation markers, in addition, revealed high expression of active caspase 3 in the outer-layer epithelial cells, and proliferating cell nuclear antigen (PCNA) in the middle and basal layer epithelial cells. High ChE activity in caspase 3-positive cells in the outer layer of the epidermis and low in PCNA-positive cells in middle and basal layers could point towards the possible involvement of ChEs in cell death and their final extrusion from skin surface.

Targeted Smart pH and Thermoresponsive N,O-Carboxymethyl Chitosan Conjugated Nanogels for Enhanced Therapeutic Efficacy of Doxorubicin in MCF-7 Breast Cancer Cells.

In cancer treatment, developing ideal anticancer drug delivery systems to target tumor microenvironment by circumventing various physiological barriers still remains a daunting challenge. Here, in our work, a series of pH- and temperature-responsive nanogels based on poly(N-isopropylacrylamide-co-1-propene-2-3-dicarboxylate-co-2-acrylamido-2-methyl-1-propanesulfonate [poly(NIPAAm-IA-AMPS)] cross-linked by ethylene glycol dimethacrylate (EGDMA) were synthesized by random copolymerization. The molar ratio between monomer-comonomers-cross-linker was varied to fine-tune the optimum responsiveness of the nanogels. These optimized nanogels were further coupled to N,O-carboxymethyl chitosan (NOCC) stoichiometrically using EDC-NHS coupling chemistry to enhance the swelling behavior at lower pH. Interestingly, these NOCC-g-nanogels, when dispersed in aqueous media under sonication, attain nanosize and retain their high water-retention capacity with conspicuous pH and temperature responsiveness (viz. nanogel shrinkage in size beyond 35 °C and swelled at acidic pH) in vitro, as reflected by dynamic light scattering data. Doxorubicin (DOX), a potent anticancer drug, was loaded into these nanogels using the physical entrapment method. These drug-loaded nanogels exhibited a slow and sustained DOX release profile at physiological temperature and cytosolic pH. Furthermore, confocal and TEM results demonstrate that these nanogels were swiftly internalized by MCF-7 cells, and cell viability data showed preferential heightened cytotoxicity toward cancer cells (MCF-7 and MDA-MB231) compared to the MCF10A cells (human breast epithelial cell). Furthermore, intracellular DNA damage and cell cycle arrest assays suggest a mitochondrial mediated apoptosis in MCF-7 cells. This study substantiates our NOCC-g-nanogel platform as an excellent modality for passive diffusive loading and targeted release of entrapped drug(s) at physiological conditions in a controlled way for the improved therapeutic efficacy of the drug in anticancer treatment.

Radical scavenging, prolyl endopeptidase inhibitory, and antimicrobial potential of a cultured Himalayan lichen Cetrelia olivetorum.

CONTEXT: Lichens are source of natural bioactive compounds which are traditionally used to cure a variety of ailments. OBJECTIVE: The objective of this study is to assess free radical scavenging, prolyl endopeptidase inhibitory (PEPI), and antimicrobial potential of a high altitude lichen species Cetrelia olivetorum (Nyl.) W. L. Culb. & C. F. Culb (Parmeliaceae). MATERIALS AND METHODS: Lichen C. olivetorum has been cultured in vitro, and optimized culture conditions were implemented in bioreactor to obtain high quantity of biomass for the study of radical scavenging, PEPI, and antimicrobial activities. Radical scavenging activity of methanol extract of Cetrelia olivetorum (MECO) was tested at 100 µg/mL, PEPI activity at 25 and 50 µg/mL, and antimicrobial activity at 5, 25, 50, and 100 µg/mL conc. All the biological activities of natural thallus extract and its derived culture extract were evaluated spectrophotometrically. RESULTS: Murashige and Skoog medium supplemented with 3% glucose and 100 ppb indole-3-butyric acid (IBA) supported biomass growth at flask level and yielded 5.095 g biomass in bioreactor. MECO of both the cultured and the natural lichen exhibited half inhibiting concentration (IC50) for radical scavenging activities in the range of 50-60 µg/mL, whereas the IC50 value of standard antioxidants was found to be in the range of 12-29 µg/mL. The IC50 value of lichen extract for PEPI activity was 144-288 µg/mL, whereas the IC50 value of standard prolyl endopeptidase inhibitor, Z-pro-prolinal, was 57.73 µg/mL. As far as the antimicrobial activity of MECO is concerned, minimum inhibitory concentration (MIC) value of lichen extracts against tested microorganisms was obtained in the range of 50-104 µg/mL and found to be more effective than commercially available standard erythromycin. DISCUSSION: Murashige and Skoog medium containing IBA was found to be suitable for maximum biomass production of C. olivetorum under bioreactor conditions. The cultured lichen biomass extract also showed antioxidant, PEPI, and antimicrobial potential. CONCLUSION: The present study indicates therapeutic potential of Himalayan lichen C. olivetorum against neurodegenerative diseases owing to its radical scavenging, PEPI, and antimicrobial activities. Further, the result encourages its commercial exploitation through mass culture for production of its bioactive components and their use in pharmaceutical and nutraceutical industries.

Growth promoting effects of some lichen metabolites on probiotic bacteria.

In the present study, the extract of four natural lichen species Canoparmelia eruptens, Everniastrum cirrhatum, Parmotrema austrosinense and Rimelia cetrata were studied for the source of natural antioxidant and their purified secondary metabolites were evaluated for growth promoting effects on probiotic bacteria Lactobacillus casei. The methanolic fraction of lichen species showed moderate to high antioxidant activity in the order P. austrosinense > E. cirrhatum > C. eruptens > R. cetrata. The lichen metabolites showed antioxidant activity with an IC50 values (µg/ml); lecanoric acid 79-95, salazinic 88-108, atranorin 100-116 and consalazinic acid 119-125. As far as the growth promoting effects of lichen metabolites on L. casei is concerned, lecanoric acid at 100 µg/ml conc. showed high growth stimulating activity in terms of increased dry matter of biomass (56.08 mg) of L. casei. Other lichen metabolites; salazinic acid, atranorin and consalazinic acid produced relatively less dry biomass 43.98 mg, 41.1 mg, 40.68 mg, respectively. However, standard antioxidants butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and Trolox after 36 h produced 39.04-47.81 mg dry biomass. At lower pH the growth promoting activity of lichen metabolites was found stable.

Severe non-hepatic hyperammonaemic encephalopathy in an immunocompromised adolescent with enterocolitis.

Non-hepatic causes of hyperammonaemia are uncommon relative to hepatic aetiologies. An adolescent female was admitted to the hospital with a diagnosis of very severe aplastic anaemia. During her treatment with immunosuppressive therapy, she developed neutropenic enterocolitis, pseudomonal bacteraemia and hyperammonaemia. A combination of intermittent haemodialysis and high-volume continuous veno-venous haemodiafiltration (CVVHDF) was required to manage the hyperammonaemia. Despite a thorough investigation, there were no hepatic, metabolic or genetic aetiologies identified that explained the hyperammonaemia. The hyperammonaemia resolved only after the surgical resection of her inflamed colon, following which she was successfully weaned off from the renal support. This is a novel case report of hyperammonaemia of non-hepatic origin secondary to widespread inflammation of the colon requiring surgical resection in an immunocompromised patient. This case also highlights the role of high-volume CVVHDF in augmenting haemodialysis in the management of severe refractory hyperammonaemia.

Computational Prediction of Potential Vaccine Candidates From tRNA Encoded peptides (tREP) Using a Bioinformatic Workflow and Molecular Dynamics Validations.

Transfer RNAs (tRNA) are non-coding RNAs. Encouraged by biological applications discovered for peptides derived from other non-coding genomic regions, we explore the possibility of deriving epitope-based vaccines from tRNA encoded peptides (tREP) in this study. Epitope-based vaccines have been identified as an effective strategy to mitigate safety and specificity concerns observed in vaccine development. In this study, we explore the potential of tREP as a source for epitope-based vaccines for virus pathogens. We present a computational workflow that uses verified data sources and community-validated predictive tools to produce a ranked list of plausible epitope-based vaccines starting from tRNA sequences. The top epitope, bound to the predicted HLA molecule, for the virus pathogen is computationally validated through 200 ns molecular dynamics (MD) simulations followed by binding free energy calculations. The simulation results indicate that two tRNA encoded epitope-based vaccines, RRHIDIVV and IMVRFSAE for Mamastrovirus 3 and Norovirus GII, respectively, are likely candidates. Peptides originating from tRNAs provide unexplored opportunities for vaccine design. Encouraged by our previous experimental study, which established the inhibitory properties of tREPs against infectious parasites, we have proposed a computationally validated set of peptides derived from tREPs as vaccines for viral pathogens.

Characterization of a Myeloid Differentiation Factor 2-Derived Peptide that Facilitates THP-1 Macrophage-Mediated Phagocytosis of Gram-Negative Bacteria.

Myeloid differentiation factor 2 (MD2), the TLR4 coreceptor, has been shown to possess opsonic activity and has been implicated in phagocytosis and intracellular killing of Gram-negative bacteria. However, any MD2 protein segment involved in phagocytosis of Gram-negative bacteria is not yet known. A short synthetic MD2 segment, MD54 (amino acid regions 54 to 69), was shown to interact with a Gram-negative bacterial outer membrane component, LPS, earlier. Furthermore, the MD54 peptide induced aggregation of LPS and facilitated its internalization in THP-1 cells. Currently, it has been investigated if MD2-derived MD54 possesses any opsonic property and role in phagocytosis of Gram-negative bacteria. Remarkably, we observed that MD54 facilitated agglutination of Gram-negative bacteria, Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC BAA-427), but not of Gram-positive bacteria, Bacillus subtilis (ATCC 6633) and Staphylococcus aureus (ATCC 25923). The MD54-opsonized Gram-negative bacteria internalized within PMA-treated THP-1 cells and were killed over a longer incubation period. However, both internalization and intracellular killing of the MD54-opsonized Gram-negative bacteria within THP-1 phagocytes were appreciably inhibited in the presence of a phagocytosis inhibitor, cytochalasin D. Furthermore, MD54 facilitated the clearance of Gram-negative bacteria E. coli (ATCC 25922) and P. aeruginosa (ATCC BAA-427) from the infected BALB/c mice whereas an MD54 analog, MMD54, was inactive. Overall, for the first time, the results revealed that a short MD2-derived peptide can specifically agglutinate Gram-negative bacteria, act as an opsonin for these bacteria, and facilitate their phagocytosis by THP-1 phagocytes. The results suggest that the MD54 segment could have a crucial role in MD2-mediated host-pathogen interaction involving the Gram-negative bacteria.

Corannulene Amino Acid-Derived Water-Soluble Amphiphilic Buckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents.

To date, the use of corannulene has been restricted in the area of material science, but its application in biomedical research has yet to be established due to its nonsolubility in an aqueous environment and synthetic infeasibility. Herein, we detail the development of a new family of highly curved π-conjugated corannulene-containing unnatural α-amino acid (CAA) derivatives to overcome this challenge. These CAAs have been extended as novel constituents for the synthesis of corannulene-containing water-soluble cationic peptides (CCPs), which display inhibitory activity against broad-spectrum pathogenic bacteria along with drug-resistant bacteria via a membrane-damaging mechanism. Importantly, several of the synthesized peptides were found to be appreciably nonhemolytic against hRBCs and noncytotoxic against mammalian 3T3 cells. In vivo efficacy studies of the potent and least cytotoxic peptide 6a demonstrated clearance of bacteria from the spleen, liver, lung, and blood of mice infected with S. aureus ATCC 25923.

Pharmacological evaluation of hyperin for antihyperglycemic activity and effect on lipid profile in diabetic rats.

Antihyperglycemic potential of hyperin at 25 and 50 mg/kg doses for 30 days to streptozotocin induced diabetic rats has been reported. In oral glucose tolerance test, hyperin treated rats showed a significant reduction in blood glucose level after 120 min. It was found that hyperin exhibited dose dependent and significant antihyperglycemic activity in streptozotocin induced diabetic rats which were nearly similar with standard drug glybenclamide. Activities of glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, glycosylated haemoglobin and level of serum urea and creatinine were significantly decreased in hyperin supplemented diabetic rats, dose dependently. Activities of hexokinase and glycogen synthase were increased with augmentation in liver glycogen, insulin and haemoglobin content in hyperin treated diabetic rats. General hematological parameters did not show any significant change in hyperin treated diabetic rats hence it is safe at these doses. Histopathological studies showed significant morphological changes in pancreatic beta-cells of streptozotocin induced diabetic rats. A decreased number of secretory granules of beta-cells were observed in diabetic rats and these pathological abnormalities were normalized after treatment with hyperin and standard drug glybenclamide. Further, hyperin decreases significant in serum total cholesterol, triglyceride, low density lipoprotein, very low density lipoprotein levels coupled with elevation of high density lipoprotein in diabetic rats. These results suggest that hyperin has a pivotal role in blood glucose level in streptozotocin induced hyperglycemia by improving the function of pancreatic islets and increasing glycolysis and decreasing gluconeogenesis.

Wound healing potential of flowers extracts of Woodfordia fruticosa Kurz.

Wound healing or repair is the body's natural process of regenerating dermal and epidermal tissue. Woodfordia fruticosa Kurz (Family: Lythraceae) is used traditionally in wound healing by the tribals of Chhattisgarh district. However, there is a paucity of scientific data in support. In this study, we evaluated antimicrobial activity of petroleum ether, chloroform, ethanolic and aqueous extracts against a diverse range of gram +ve and gram -ve bacteria along with pathogenic fungi. The wound healing activity of ethanolic extract was also evaluated at dose levels of 250 and 500 mg/kg body wt in rats by excision, incision and dead space wound healing models along with histopathology of wound area of skin. The ethanolic extract showed potent wound healing activity, as evident from the increase in the wound contraction and breaking strength in dose-dependent manner. Treatment with ethanolic extract (250 and 500 mg/kg body wt) showed significant dose-dependently decrease in epithelization period and scar area. Hydroxyproline, hexuronic acid and hexosamine contents, the important constituents of extracellular matrix of healing were also correlated with the observed healing pattern. During early wound healing phase, pro-inflammatory cytokines TNF-alpha, IL-6 and anti-inflammatory cytokine IL-10 levels were found to be upregulated by the ethanolic extract treatment. The ethanolic extract exhibited a strong and broad spectrum antimicrobial activity, as compared to other extracts. It showed very low Minimum inhibitory concentration (MIC) values and inhibited the growth of E. coli, Staphylococcus aureus and Candida albicans in concentration of 2.5 microg/disc. Thus, the results of the present study demonstrated the strong wound healing potential and antimicrobial activities of W. fruticosa, flowers, supporting the folklore use of the plant by the tribal people of Chhattisgarh district.

A Mechanistic Review on Phytomedicine and Natural Products in the Treatment of Diabetes.

Diabetes mellitus is a metabolic syndrome of excess glucose levels in the blood. It may be due to glucose intolerance by the tissues and inadequate insulin production from pancreatic ß- cells. However, diabetic complication includes cardiovascular and kidney diseases, eye, skin, and foot complications, and neuropathy. The intention behind writing this article was to gather recent information regarding the use of ancient traditional medicinal plants having recent importance in treating diabetes. Several therapies are available for curing the condition based on severity and type of diabetes. Although pharmacological treatments are effective and economical, drugs are associated with unwanted side effects and physiological complications on long-term use. Interestingly, herbs and herbal plants have been used since ancient times against diabetes worldwide. Its importance still exists due to medicinal plants' effectiveness and safety profile in treating various diseases. In this article, we searched online databases, including PUBMED, SCOPUS, MEDLINE, and traditional resources, for collecting information regarding the use of plants against diabetes. We described the pathophysiology of the disease and incorporated plant sources and their chemical constituents responsible for antidiabetic activity with their mechanism in reducing blood glucose levels. The present article may be very helpful for researchers and professionals whose work is inclined towards diabetes and in search of lead compounds for the development of a suitable drug.

Effect of Multiple Doses of Sparsentan on the Single-Dose Pharmacokinetics of Dapagliflozin: An Open-Label Drug-Drug Interaction Study in Healthy Adults.

Sparsentan is a single-molecule dual antagonist of the endothelin type A receptor and angiotensin II type 1 receptor under investigation for the treatment of focal segmental glomerulosclerosis and immunoglobulin A nephropathy. Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, has recently been indicated in chronic kidney disease. Sparsentan may be considered for concomitant use with dapagliflozin. The purpose of this open-label, 1-sequence crossover study was to determine whether drug-drug interactions between sparsentan and dapagliflozin affect dapagliflozin pharmacokinetics (PK). In addition, exposure to the inactive metabolite of dapagliflozin, dapagliflozin-3-O-glucuronide, was used to evaluate the effect of sparsentan on the primary metabolizing enzyme of dapagliflozin, uridine 5'-diphospho-glucuronosyltransferase 1A9. The study included 22 healthy adults treated with 10 mg of dapagliflozin on day 1, and 800 mg/day of sparsentan on days 5-14, with a 10-mg dose of dapagliflozin coadministered on day 11. PK samples were taken for dapagliflozin, dapagliflozin-3-O-glucuronide, and sparsentan before and after treatment throughout the study. Steady-state concentrations of sparsentan following daily dosing did not affect the PK of single-dose dapagliflozin in healthy adults. Dapagliflozin-3-O-glucuronide PK suggests a minimal effect of sparsentan on metabolism of dapagliflozin by uridine 5'-diphospho-glucuronosyltransferase 1A9. No deaths, serious adverse events, or unusual safety signals occurred. Results suggest dapagliflozin PK is not affected by sparsentan daily dosing.

Estimation of spectroscopic parameters and TL glow curve analysis of Eu3+-activated CaY2O4 phosphor.

The solid-state reaction method was utilised to create a down-conversion phosphor in an air environment in CaY2O4:Eu3+ nanocrystalline material. The calcination temperature was set at 1000 °C, and the sintering temperature was set at 1300 °C. Following annealing, confirmation of the crystallinity quality of the phosphor was accomplished by the use of X-ray diffraction analysis. The particle size was predicted to be 43.113 nm using Scherrer's formula. To produce down-conversion luminescence spectra, an excitation wavelength of 247 nm was applied with a fluorescence spectrophotometer. The PL got increasingly intense as the concentration of the dopant increased. The maximum intensity was measured at 2.0 mol% of Eu3+ ion, which gradually decreased as the concentration increased because of concentration quenching. To analyse spectrophotometric peak determinations, the approach developed by the Commission Internationale de l'Éclairage (CIE) was used. Thermoluminescence (TL) glow curve analysis of the CaY2O4:Eu3+-doped phosphor manufactured here revealed a wide TL centred at 225 °C, which comprised of so many peaks that may be extracted by the computerised glow curve deconvolution (CGCD) approach using glow-fit software. The associated kinetic parameters were then determined. The prepared phosphor may be useful for application in various display devices upon excitation by 247 nm; the prominent 613 nm peak of the Eu3+ ion (5D0 → 7F2) electric dipole transition features a red component. CaY2O4:Eu3+ phosphors show promise as materials for potential use in phosphor-converted white LEDs in the field of solid-state lighting technology. The linear connection that the TL glow curve has with UV dose provides evidence for its possible use in dosimetry.

Optimizing the luminescence efficiency of an europium (Eu3+) doped SrY2O4 phosphor for flexible display and lighting applications.

This research paper reports the synthesis and luminescence study of an Eu3+ activated SrY2O4 phosphor prepared by a modified solid-state reaction method with varying concentrations of Eu3+ ions (0.1-2.5 mol%). X-ray diffraction (XRD) revealed the orthorhombic structure and Fourier transform infrared spectroscopy (FTIR) methods were used to analyse the produced phosphors. Photoluminescence emission and excitation spectra were recorded for varying concentrations of Eu3+ ions, and an optimum concentration of 2.0 mol% was found to produce the highest intensity. Under 254 nm excitation the emission peaks were found to be at 580 nm, 590 nm, 611 nm and 619 nm, corresponding to transitions at 5D0 → 7F0, 5D0 → 7F1, and 5D0 → 7F2 respectively. Because of Eu3+ inherent luminosity, these emission peaks indicate radiative transitions between excited states of ions, making them useful for developing white light-emitting phosphors for optoelectronic and flexible display applications. The 1931 CIE (x, y) chromaticity coordinates were calculated from the photoluminescence emission spectra and found to be near white light emission, indicating the potential application of the prepared phosphor for light emitting diodes (white component). TL glow curve analysis was also performed for various concentrations of doping ions and UV exposure times, and a single broad peak was observed at 187 °C. Using the computerised glow curve deconvolution (CGCD) method, kinetic parameters were computed.

Antihyperglycemic activity of Woodfordia fruticosa (Kurz) flowers extracts in glucose metabolism and lipid peroxidation in streptozotocin-induced diabetic rats.

The ethanolic extract of W. fruticosa flowers (250 and 500 mg/kg) significantly reduced fasting blood glucose level and increased insulin level after 21 days treatment in streptozotocin diabetic rats. The extract also increased catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase activities significantly and reduced lipid peroxidation. Glycolytic enzymes showed a significant increase in their levels while a significant decrease was observed in the levels of the gluconeogenic enzymes in ethanolic extract treated diabetic rats. The extract has a favourable effect on the histopathological changes of the pancreatic beta-cells in streptozotocin induced diabetic rats. The results suggest that W. fruticosa possess potential antihyperglycemic effect by regulating glucose homeostasis and antioxidant efficacy in streptozotocin-induced diabetic rats.

Impact of age and gender disparity on CD4+ cell counts to control disease progression using specific HAART in HIV-1 positive patients: A case-control study.

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) is composed of several drugs in the antiretroviral class to better treat human immunodeficiency virus type 1 (HIV-1) patients. The estimation of CD4+ T cell counts and HIV-1 viral load in plasma is required to evaluate the treatment success of a specific HAART. METHODOLOGY: The study included the effects of NRTIs (nucleoside reverse transcriptase inhibitors) and novel protease inhibitors (HAART) on normal control subjects and HIV-1 positive subjects from SGPGIMS, Lucknow, with different age groups and genders. Furthermore, the study was conducted by the estimation of HIV through ELISA, measurement of absolute CD4+ cell count, and the measurement of viral load through qRT-PCR. Furthermore, NRTIs (Retrovir and Epivir) were administered orally one tablet daily in the morning followed by newly FDA-approved protease inhibitors (fosamprenavir and darunavir) orally in the evening at the same dose. Furthermore, CD4+T cell counts and HIV-1 viral load were investigated and correlated in patients with different genders and age groups. RESULT: Administration of NRTIs and novel protease inhibitors (HAART) in HIV patients had a significant effect on the CD4+ cell count in various age intervals among males and females. The mean comparison of viral load distribution based on gender in CD4 +ve patients in the case group exhibited a viral load higher in females compared to males, indicating a statistically significant difference between males and females (p<0.05). A notable association between virological and immunological parameters was observed with a reciprocal relationship between viral load and CD4 cell count in CD4 +ve patients, demonstrating multiple correlation coefficients with an R-value of 0.853. CONCLUSION: The administration of specific HAART (NRTIs and novel protease inhibitors) in HIV patients had a notable improvement in the CD4+ cell count and viral load with significant age and gender disparity.