Forearmed is forewarned: A prospective intervention observational time-series study of patient empowerment for ultrasound-guided peripheral intravenous access.

OBJECTIVE: Ultrasound (US) is a valuable adjunct to improve the success rates of difficult peripheral intravenous cannula (PIVC) insertions but is usually clinician initiated. The present study assessed for any change in clinician practice resulting from interventions aimed at empowering patients to advocate for early use of US if they self-identified as having difficult PIVC access. METHODS: This was a prospective observational time-series study using a rapid quality improvement (RQI) framework. Three ED waiting room intervention strategies (printed media, video and wristband) were tested over three 2-week periods at a large teaching hospital. The impact of each intervention was assessed at eight time points during each intervention and compared to a pre-intervention baseline period using trend and time-series analysis. RESULTS: A total of 1611 PIVC insertions were surveyed over 42 time points. The proportion of US-guided PIVC insertions was highest during Intervention 3 (wristbands; 5.5%) but all proportions remained below baseline (6.5%). Trend analysis identified an increasing frequency of US use during Intervention 1 (printed media, P = 0.01). However, no statistically significant trends were observed within the periods. CONCLUSIONS: This is the first prospective study to assess the effect of various interventions to empower patients to self-identify as having difficult PIVC access and advocate for the use of US-guidance. The present study was indeterminate: no intervention tested in the present study noticeably influenced clinical practice, potentially attributable to the study design and confounding factors. This innovative study serves as a pilot for future research into patient empowerment, which is currently lacking in the literature.

Resurrection of Nalidixic Acid: Evaluation of Water-Based Nanoformulations as Potential Nanomedicine.

Resistance to quinolone antibiotics has been a serious problem ever since nalidixic acid was introduced into clinical medicine. Over time, resistance of pathogenic microbes to nalidixic acid led to the design of novel variants to revive its potential application. In the present work, a series of eight nanoformulations of nalidixic acid-based diacyl and sulfonyl acyl hydrazine derivatives were prepared. All nanoformulations were found to be stable at different storage temperatures. Antibacterial and anticandida activity of the eight nanoformulations presented encouraging results when compared with their non-nano parent counterparts. The nanoformulations of chloro, furanyl, and sulfonyl acyl substituted derivatives of nalidixic acid displayed most promising results (MIC ranging from 50 to 100 µg mL-1) against the tested bacteria and yeast. Among the screened bacteria, Acinetobacter baumannii displayed maximum sensitivity to the above nanoformulations. Biosafety study on the mammalian model-wax moth, Galleria mellonella-showed that all eight prepared nanoformulations were absolutely nontoxic to the larvae and subsequent pupae and hence may likely have no or low toxicity against mammalian systems.

Development of a novel myconanomining approach for the recovery of agriculturally important elements from jarosite waste.

In this study, an ecofriendly and economically viable waste management approach have been attempted towards the biosynthesis of agriculturally important nanoparticles from jarosite waste. Aspergillus terreus strain J4 isolated from jarosite (waste from Debari Zinc Smelter, Udaipur, India), showed good leaching efficiency along with nanoparticles (NPs) formation under ambient conditions. Fourier-transform infrared spectroscopy (FT-IR) and transmission electron microscopy (TEM) confirmed the formation of NPs. Energy dispersive X-ray spectroscopy (EDX analysis) showed strong signals for zinc, iron, calcium and magnesium, with these materials being leached out. TEM analysis and high resolution transmission electron microscopy (HRTEM) showed semi-quasi spherical particles having average size of 10-50nm. Thus, a novel biomethodology was developed using fungal cell-free extract for bioleaching and subsequently nanoconversion of the waste materials into nanostructured form. These biosynthesized nanoparticles were tested for their efficacy on seed emergence activity of wheat (Triticum aestivum) seeds and showed enhanced growth at concentration of 20ppm. These nanomaterials are expected to enhance plant growth properties and being targeted as additives in soil fertility and crop productivity enhancement.

Synthesis, biological activities and SAR studies of novel 1-Ethyl-7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid based diacyl and sulfonyl acyl hydrazines.

BACKGROUND: Diacyl hydrazines have attracted significant interest in medicine, pesticide chemistry and material science. It is an important class of insect growth regulators. In this study, acyl hydrazine, the essential active group was incorporated in to nalidixic acid with the aim of combining the active groups to generate more potent agrochemical. RESULTS: Various nalidixic acid based diacyl and sulphonyl acyl hydrazines derivatives were synthesized and characterized by spectral techniques. These compounds were screened for the antifungal activity against five pathogenic fungi, nitrification inhibitory activity and insect growth regulator (IGR) activity against Spodoptera litura. The fungicidal activity was screened against R. bataticola, S. rolfsii, R. solani, F. oxysporum and A. porri. Most of the compounds showed moderate to good antifungal activity against A. porri (ED50 = 29.6-495.9 µg/mL). All the compounds showed significant nitrification inhibitory activity at 5% level. IGR activity was examined by feeding method against S. litura. CONCLUSION: The study revealed that a few compounds possessed good activity against three different pests namely certain fungus, soil bacteria and insect, among which, compound 37 (R' = 4-chlorophenyl) behaved the best.

Synthesis of novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones and evaluation of their biocidal effects.

Novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones have been synthesized in high yields by treatment of the corresponding oxo analogs with Lawesson's reagent. The structure has been confirmed by X-ray analysis. The compounds were tested for in vitro antifungal activity against Rhizoctonia bataticola, Sclerotium rolfsii, Fusarium oxysporum and Alternaria porii. The compounds exhibited moderate to good activity against all pathogens. Insecticidal activity of these compounds against Spodoptera litura was observed to be comparable to commercial pyrethroid insecticide, cypermethrin. The urease inhibitory activity has also been studied.

Synthesis of 2-furyl-4-arylidene-5(4H)-oxazolones as new potent antibacterial agents against phyto-pathogenic and nitrifying bacteria.

Crop losses due to bacterial pathogens are a major global concern. Most of the available pesticides for these pathogens suffer from various drawbacks such as complicated synthesis, high cost, high toxicity, pesticide resistance and environmental hazards. To overcome these drawbacks, the present study was undertaken to find a potent bactericide. Therefore, a series of compounds comprising bioactive furyl and oxazolone rings was synthesized under microwave irradiation and screened for in vitro antibacterial activity. The reactions were completed in fewer than 2 minutes with minimal use of solvents and resulted in high yields. These compounds were screened for antibacterial activity against plant pathogens, Xanthomonas oryzae, Ralstonia solanacearum and nitrifying bacteria, Nitrosomonas species under laboratory conditions. Five compounds were active as antibacterial agents against Xanthomonas oryzae and Ralstonia solanacearum. However, all compounds were effective against the Nitrosomonas species and the best one was 2-furyl-4-(3-methoxy-4-hydroxybenzylidene)-5(4H)-oxazolone. The study revealed the fast and environmentally friendly synthesis of bioactive title compounds, which also hold promise to be used as prototypes for the discovery of potent analogues.

Synthesis of novel nalidixic acid-based 1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives as potent antibacterial agents.

Novel nalidixic acid-based 1,3,4-thia(oxa)diazoles, their thio ethers, sulfones, bis mercapto, and Mannich bases were synthesized and characterized by Infrared spectra, (1) H NMR, (13) C NMR, and elemental analysis. These compounds were evaluated for their antibacterial activity against two Gram-positive and three Gram-negative bacteria. The preliminary bioassay showed that most of the compounds had better antibacterial activity than the parent compounds, 1,3,4-thia(oxa)diazoles, at the dosage 50µg/mL toward five test bacteria. Four Mannich bases of nalidixic acid-based 1,3,4-thiadiazole exhibited maximum antibacterial activity against Bacillus subtilis, Klebsiella pneumoniae, and Pseudomonas aeruginosa with minimum inhibitory concentration in the range of 6.25-125µg/mL.

Synthesis, antimicrobial evaluation and QSAR analysis of novel nalidixic acid based 1,2,4-triazole derivatives.

Novel nalidixic acid based 1,2,4-triazole derivatives were synthesized and characterized using spectral techniques like (1)H NMR, (13)C NMR, IR and mass spectrometry. All these compounds were screened for antimicrobial activity against five bacteria and two pathogenic fungi. Most of these compounds showed better antimicrobial activity than the parent compound, 4-amino-5-mercapto-1,2,4-triazole. Among all the screened compounds, 3-{6-(2-chlorophenyl)-1,2,4-triazolo [3,4-b] [1,3,4]thiadiazol-3-yl}-1-ethyl-7-methyl-1,8-naphthyridin-4(1H)-one (23) was emerged as promising antimicrobial agent (MIC = 16 µg/mL). Quantitative structure activity relationship (QSAR) analysis was carried out using various distance-based topological indices, steric and hydrophobic parameters. Based on the QSAR analysis it is indicative that lipophilic and steric parameters are the pre-requisites for these molecules to act as potent antimicrobial agents.

Synthesis of nalidixic acid based hydrazones as novel pesticides.

Thirty-one substituted hydrazones of nalidixic acid hydrazide were synthesized and characterized by spectral techniques. These compounds were evaluated for various biological activities, namely, fungicidal, insecticidal, and nitrification inhibitory activities. The antifungal activity was evaluated against five pathogenic fungi, namely, Rhizoctonia bataticola , Sclerotium rolfsii , Rhizoctonia solani , Fusarium oxysporum , and Alternaria porii . They showed maximum inihibition against A. porii with ED(50) = 34.2-151.3 microg/mL. The activity was comparable to that of a commercial fungicide, hexaconazole (ED(50) = 25.4 microg/mL). They were also screened for insecticidal activity against third-instar larvae of Spodoptera litura and adults of Callosobruchus maculatus and Tribollium castaneum . Most of them showed 70-100% mortality against S. litura through feeding method at 0.1% dose. These compounds were not found to be effective nitrification inhibitors.

Schiff bases as potential fungicides and nitrification inhibitors.

A number of substituted Schiff bases were synthesized and characterized by (1)H NMR and mass spectrometry. These compounds were screened for antifungal activity in vitro against pathogenic fungi, namely, Sclerotium rolfsii and Rhizoctonia bataticola, and for their effect on nitrification inhibition under laboratory conditions. Maximum antifungal activity was exhibited by (2,4-dichlorobenzylidene)-(2,4,5-trichlorophenyl)-amine and (3-nitrobenzylidene)-(2,4,5-trichlorophenyl)-amine against both fungi (ED(50) with range from 3 to 24 microg/mL). Maximum nitrification inhibition (NI) was exhibited by (2,4-dichlorobenzylidene)-(2-fluorophenyl)-amine, (4-fluorophenyl)-(3-nitrobenzylidene)-amine, (2,6-dichlorobenzylidene)-(4-fluorophenyl)-amine, and (2,6-dichlorobenzylidene)-(3 fluorophenyl)-amine (NI in the range 91-96%).

Molecular determinants for differential membrane trafficking of PMCA1 and PMCA2 in mammalian hair cells.

The plasma membrane Ca2+-ATPase-2 (PMCA2) is expressed in stereocilia of hair cells of the inner ear, whereas PMCA1 is expressed in the basolateral plasma membrane of hair cells. Both extrude excess Ca2+ from the cytosol. They are predicted to contain ten membrane-spanning segments, two large cytoplasmic loops as well as cytosolic N- and C-termini. Several isoform variants are generated for both PMCA1 and PMCA2 by alternative splicing, affecting their first cytosolic loop (A-site) and their C-terminal tail. To understand how these isoforms are differentially targeted in hair cells, we investigated their targeting regions and expression in hair cells. Our results show that a Leu-Ile motif in 'b'-tail splice variants promotes PMCA1b and PMCA2b basolateral sorting in hair cells. Moreover, apical targeting of PMCA2 depends on the size of the A-site-spliced insert, suggesting that the conformation of the cytoplasmic loop plays a role in apical targeting.