Phenotypic assessment of antiviral activity for spiro-annulated oxepanes and azepenes.

Evolutionary potential of viruses can result in outbreaks of well-known viruses and emergence of novel ones. Pharmacological methods of intervening the reproduction of various less popular, but not less important viruses are not available, as well as the spectrum of antiviral activity for most known compounds. In the framework of chemical biology paradigm, characterization of antiviral activity spectrum of new compounds allows to extend the antiviral chemical space and provides new important structure-activity relationships for data-driven drug discovery. Here we present a primary assessment of antiviral activity of spiro-annulated derivatives of seven-membered heterocycles, oxepane and azepane, in phenotypic assays against viruses with different genomes, virion structures, and genome realization schemes: orthoflavivirus (tick-borne encephalitis virus, TBEV), enteroviruses (poliovirus, enterovirus A71, echovirus 30), adenovirus (human adenovirus C5), hantavirus (Puumala virus). Hit compounds inhibited reproduction of adenovirus C5, the only DNA virus in the studied set, in the yield reduction assay, and did not inhibit reproduction of RNA viruses.

Residue behavior and consumer risk assessment of spirotetramat and chlorpyrifos on cabbage heads and cropped soil.

A field experiment following good agricultural practices was laid out to study the dissipation of spirotetramat (90 g a.i. ha-1 and 180 g a.i. ha-1) and chlorpyrifos (400 g a.i. ha-1 and 800 g a.i. ha-1) on cabbage heads and soil. Samples were processed using quick, easy, cheap, effective, rugged, and safe (QuEChERS) method for residue estimation of spirotetramat and chlorpyrifos, which were further detected using HPLC-PDA and GC-FPD respectively. The residues of spirotetramat on cabbage heads reached below detection limit (BDL) (< 0.05 mg kg-1) on 7th and 10th day and for chlorpyrifos, BDL (< 0.01 mg kg-1) was achieved on 10th and 15th day for X and 2X dose, respectively. On 20th day after second spray, residues in soil were found to be BDL for both the pesticides. Half-life of spirotetramat and chlorpyrifos was found to be 3 and 2 days, respectively while a safe pre-harvest interval (PHI) of 9 days for spirotetramat and 10 days for chlorpyrifos is suggested on cabbage. The dietary risk assessment studies for various age groups of Indian population, ascertained safety of treated cabbage heads for consumption, as current study revealed that hazard quotient (HQ) < 1 and theoretical maximum dietary intake (TMDI) < maximum permissible intake (MPI) for both the pesticides at respective PHI.

Prevalence of youth experiencing homelessness and its association with suicidal thoughts and behaviors: Findings from a population-based study.

Although various studies have examined factors associated with suicidal behaviors among youth, few studies have investigated the association between youth experiencing homelessness (YEH) and suicidal thoughts and behaviors (STBs) using a large nationally representative sample. The objectives of this study were to investigate prevalence of YEH and its association with STBs. Data for this study came from the 2021 Youth Risk Behavior Survey. An analytic sample of 17,033 youth aged 14-18 (51.7 % male) was analyzed using binary logistic regression. Of the 17,033 youth examined, 3 % experienced homelessness during the past 30 days, 21.3 % experienced suicidal ideation, 17.3 % made a suicide plan, and 10.9 % attempted suicide during the past 12 months. Controlling for demographic characteristics and feeling sad or hopeless, YEH was associated with 2.48 times higher odds of experiencing suicidal ideation (AOR=2.48, p<.001), 2.46 times higher odds of making a suicide plan (AOR=2.46, p<.001), and 4.38 times higher odds of making a suicide attempt (AOR=4.38, p<.001). The findings of this study highlight the importance of identifying youth who are at risk of experiencing homelessness to ensure early interventions are put in place to prevent suicidal behaviors.

Cost-Effectiveness Evaluation of Oral CGRP Antagonists, Atogepant and Rimegepant, for the Preventative Treatment of Episodic Migraine: Results from a US Societal Perspective Model.

BACKGROUND AND OBJECTIVES: Two oral calcitonin gene-related peptide (CGRP) antagonists, atogepant and rimegepant, were approved in 2021 for the preventive treatment of episodic migraine (EM), yet no formal cost-effectiveness analysis has been published. The objective of this study was to evaluate the cost-effectiveness of atogepant 60 mg and rimegepant 75 mg compared with placebo. METHODS: A decision tree model was constructed over a 1-year time horizon from a US societal perspective. Patient cohorts were simulated using baseline and change from baseline monthly migraine days (MMDs) reported in the trials to incorporate responder rates and within patient response into the model. Due to heterogeneity between the trial populations, each medication was compared with its respective trial's placebo group. Direct healthcare resource costs, productivity costs, acute medication costs, and quality-of-life values were obtained from the literature. RESULTS: The atogepant cohort experienced an incremental increase in healthcare plus productivity costs of $11,978 when compared with placebo, with a gain of 0.026 quality-adjusted life-years (QALYs). This yielded an incremental cost-effectiveness ratio (ICER) of more than $450,000/QALY. The rimegepant cohort experienced an incremental increase of $21,692 when compared with placebo, with a gain of 0.024 QALYs. This yields an ICER of more than $890,000/QALY when comparing rimegepant with placebo. Cost savings between atogepant and atogepant placebo were greatest with respect to acute medication costs at $735 of savings over 1 year, followed by savings of $135 for healthcare resource utilization and $34 for productivity costs. A similar relationship was seen between rimegepant and rimegepant placebo. One-way deterministic sensitivity analysis found that monthly acquisition costs of atogepant and rimegepant had the largest impact on the ICER, respectively. CONCLUSIONS: Atogepant and rimegepant were both unable to meet generally accepted cost-effectiveness thresholds < 150,0000/QALY. Additional studies are needed to better guide decision making regarding oral CGRPs' place in therapy.

Evaluating the efficacy of different antibiotics against Neisseria gonorrhoeae: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.

BACKGROUND: With the widespread use of antibiotics, antimicrobial resistance in Neisseria gonorrhoeae is worsening. The objective of this study was to evaluate the efficacy changes of seven antibiotics in the treatment of N. gonorrhoeae by using Monte Carlo simulation combined with pharmacokinetics/pharmacodynamics/ (PK/PD). METHODS: The minimum inhibitory concentration (MIC) of antibiotics against clinical isolates from 2013 to 2020 in Nanjing, China, was determined by agar dilution method. The probability of target attainment (PTA) was estimated at each MIC value and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. RESULTS: All dosage regimens of seven antibiotics achieved PTAs ≥ 90% for MIC ≤ 0.06 µg/ml. But when the MIC was increased to 1 µg/ml, PTAs at each MIC value exceeded 90% only for ceftriaxone 1,000 mg and 2,000 mg, zoliflodacin 2,000 mg and 3,000 mg. Among them, the CFR values of each dosing regimen against N. gonorrhoeae only for ceftriaxone, cefixime and zoliflodacin were ≥ 90% in Nanjing from 2013 to 2020. CONCLUSIONS: Cephalosporins are still the first-line drugs in the treatment of gonorrhea. However, the elevated MIC values of cephalosporins can lead to decline in clinical efficacy of the conventional dose regimens, and increasing the dose of ceftriaxone to 1,000 mg-2,000 mg may improve the efficacy. In addition, zoliflodacin is possible to be a potential therapeutic agent in the future.

Determination, residue analysis and risk assessment of thiacloprid and spirotetramat in cowpeas under field conditions.

The dissipation and residue levels of thiacloprid, spirotetramat and its four metabolites residues in cowpeas were investigated under field conditions. The QuEChERS technique with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was used to detect thiacloprid, spirotetramat and its four metabolites residues content in cowpeas. The recoveries were 81.3-95.1% at a spike level of 0.005-0.5 mg/kg, the relative standard deviations (RSDs) were 2.1-9.5%. The dissipation kinetics data showed that thiacloprid and spirotetramat in cowpeas were degraded with the half-lives of 1.14-1.54 days and 1.25-2.79 days. The terminal residues of thiacloprid and spirotetramat were 0.0255-0.4570 mg kg-1 and 0.0314-0.3070 mg kg-1 after application 2 times with a pre-harvest interval (PHI) of 3 days under the designed dosages. The chronic and acute dietary exposure assessment risk quotient (RQ) values of thiacloprid in cowpeas for different consumers were 2.44-4.41% and 8.72-15.78%, respectively, and those of spirotetramat were 1.03-1.87% and 0.18-0.32%, respectively, all of the RQ values were lower than 100%. The dietary risk of thiacloprid through cowpeas to consumers was higher than spirotetramat. The results from this study are important reference for Chinese governments to develop criteria for the safe and rational use of thiacloprid and spirotetramat, setting maximum residue levels (MRLs), monitoring the quality safety of agricultural products and protecting consumer health.

Residual characteristics and safety assessment of the insecticides spiromesifen and chromafenozide in lettuce and perilla.

This study was performed to investigate the residual characteristics, safety assessment, and pre-harvest interval (PHI) of spiromesifen and chromafenozide in lettuce (Latuca sativa L.) and perilla (Perilla frutescens (L.) Britton) leaves. Samples were harvested periodically, extracted using QuEChERS method, and analyzed by LC-MS/MS. Average recoveries of spiromesifen and its metabolite BSN2060-enol and chromafenozide were ranged from 80.6 to 107.9%, with relative standard deviation < 10%. Spiromesifen and cromafenozide initial residues in lettuce were dissipated to 81.45 and 95.52% after 7 days, with half-lives of 2.89 and 1.69 days respectively. Values in perilla leaves were 76.68 and 61.27% after the same period, with half-lives of 4.25 and 6.30 days, respectively. Risk assessment results showed that %ADI (acceptable daily intake) of spiromesifen and chromafenozide was 6.83 and 0.56, in lettuce and 4.60 and 0.25% in perilla leaves, respectively. Theoretical maximum daily intakes of spiromesifen and chromafenozide were 67.49 and 3.43%, respectively, indicating that residues of both compounds pose no considerable health risks to consumers. This study provides data for setting maximum residue limits and PHIs for the safe use of spiromesifen and chromafenozide in lettuce and perilla.

Budget impact and pharmacy costs with targeted use of oliceridine for postsurgical pain in patients at high risk of opioid-related adverse events.

BACKGROUND: Oliceridine, a new class of µ-opioid receptor agonist, may be associated with fewer opioid-related adverse events (ORAEs) due to its unique mechanism of action. Thus, it may provide a cost-effective alternative to conventional opioids such as morphine. PATIENTS AND METHODS: Using a decision tree with a 24-hour time horizon, we calculated costs for medication and management of the three most common AEs (oxygen saturation <90%, vomiting, somnolence) following postoperative oliceridine or morphine in high-risk patients. Costs were enumerated as differences in cost of analgesics and resource utilization in the first 24 hours post-surgery. An economic model compared expected AEs and costs in a blended cohort where elderly/obese patients at higher risk for ORAEs received oliceridine while those presumed to be at lower risk received morphine with a cohort that received morphine alone. RESULTS: In high-risk patients, use of oliceridine resulted in overall savings of $363,944 (in 1,000 patients). Implementing a targeted approach of oliceridine utilization in patients with high risk for ORAEs can save a typical hospital system $122,296 in total cost of care. CONCLUSION: Use of oliceridine in postoperative care among patients at high risk provides a favorable health economic benefit compared to the use of morphine.

Oliceridine, a new class of opioid analgesics, administered directly into a vein, is a unique medication in that it provides pain relief equivalent to morphine and may have less costly side effects. It is given in a hospital/clinic or surgery center for the treatment of postoperative pain and can reduce costs compared to other opioid analgesics, possibly due to less side effects. An economic model was developed that compares morphine to oliceridine in patients more likely to experience sides effects due to traditional pain medications, comparing common side effects and pain relief following surgery. Although oliceridine costs more than morphine, in our economic model, the use of oliceridine resulted in cost savings ($363,944 US 2020 Dollars in 1,000 patients), and a positive return of investment of over 7 times, when compared to morphine.

New repurposed rolapitant in nanovesicular systems for lung cancer treatment: Development, in-vitro assessment and in-vivo biodistribution study.

Lung cancer is characterized by poor prognosis, and is considered a serious disease that causes a significant mortality. The available conventional chemotherapeutic agents suffer from several limitations; hence, new drug molecules are constantly being sought. In the current study, lipid nanovesicles (LNVs) were selected as a colloidal vehicle for encapsulation of the FDA-approved drug; rolapitant (RP), which is used particularly for the treatment of nausea and vomiting, but is repurposed for the treatment of lung cancer in the current work. RP was loaded into various LNVs (liposomes, ethosomes and transethosomes) using the thin film hydration method, and the LNVs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), storage stability and surface morphology. Besides, the in-vitro drug release, in-vitro cytotoxicity on A549 lung cancer cells, nebulization performance using next generation impactor (NGI), and the in-vivo biodistribution behavior were evaluated. The selected ethosomal and transethosomal vesicles displayed a particle size less than 400 nm, a positive charge, and EE% exceeding 90% for RP, with a sustained release pattern over 15 days. The in-vivo biodistribution results proved the high lung deposition potential of RP-LNVs with a considerable safety. Besides, the developed RP-LNVs were able to reach the metastatic organs of lung cancer, hence they were proven promising as a possible treatment modality for lung cancer.

Assessment In Vitro of the Antimalarial and Transmission-Blocking Activities of Cipargamin and Ganaplacide in Artemisinin-Resistant Plasmodium falciparum.

Artemisinin resistance in Plasmodium falciparum has emerged and spread widely in the Greater Mekong Subregion, threatening current first-line artemisinin combination treatments. New antimalarial drugs are needed urgently. Cipargamin (KAE609) and ganaplacide (KAF156) are promising novel antimalarial compounds in advanced stages of development. Both compounds have potent asexual blood stage activities, inhibit P. falciparum gametocytogenesis, and reduce oocyst development in anopheline mosquitoes. In this study, we compared the asexual and sexual stage activities of cipargamin, ganaplacide, and artesunate in artemisinin-resistant P. falciparum isolates (n = 6; K13 mutations C580Y, G449A, and R539T) from Thailand and Cambodia. Asexual blood stage antimalarial activity was evaluated in a SYBR-green I-based 72-h in vitro assay, and the effects on male and female mature stage V gametocytes were assessed in the P. falciparum dual gamete formation assay. Ganaplacide had higher activities than cipargamin and artesunate, with mean (standard deviation [SD]) 50% inhibitory concentrations (IC50s) against asexual stages of 5.6 (1.2) nM and 6.9 (3.8) nM for male gametocytes and 47.5 (54.7) nM for female gametocytes. Cipargamin had a similar potency against male and female gametocytes, with mean (SD) IC50s of 115.6 (66.9) nM for male gametocytes, 104.9 (84.3) nM for female gametocytes, and 2.4 (0.7) nM for asexual stages. Both cipargamin and ganaplacide showed significant transmission-blocking activities against artemisinin-resistant P. falciparum in vitro.

Stability and fitness cost associated with spirotetramat resistance in Oxycarenus hyalinipennis Costa (Hemiptera: Lygaeidae).

BACKGROUND: Dusky cotton bug, Oxycarenus hyalinipennis Costa (Hemiptera: Lygaeidae) is an important pest of cotton and causing economic losses to this crop. It also remains active round the year, infesting a number of host plants. Spirotetramat is a systemic insecticide and is effective against many sucking insect pests. A field collected population of O. hyalinipennis was reared in the laboratory under continuous spirotetramat selection pressure for 21 generations for the development of resistance to spirotetramat. The Spiro-Sel population was further reared for seven generations without insecticide exposure to assess the stability of spirotetramat resistance. Leaf dip method was used for the bioassays and selection. In this study, the impact of spirotetramat resistance on its stability and life history traits of Spiro-Sel, C1 (15 Spiro-Sel♀ × 15 UNSEL ♂) and C2 (15 Spiro-Sel♂ × 15 UNSEL ♀) O. hyalinipennis was assessed. RESULTS: Spiro-Sel (G21 ) population developed 2333-fold and 20.83-fold resistance compared with the susceptible and unselected (UNSEL) populations, respectively. Resistance to spirotetramat was unstable after seven generations (G28 ) when reared without exposure to any insecticide. A significant reduction in overall nymphal survival, fecundity, egg hatching and net reproductive rate of Spiro-Sel population was observed when compared with UNSEL population. Intrinsic rate of natural increase, biotic potential and mean relative growth rate were also lower in Spiro-Sel population compared to UNSEL population. The Spiro-Sel, C1 and C2 population had a relative fitness of 0.44, 0.51 and 0.44, respectively. CONCLUSION: Results of our study suggested that fitness cost is involved in the development of spirotetramat resistance. Unstable resistance and high fitness cost may provide great benefits to limit the evolution of resistance to spirotetramat in O. hyalinipennis. © 2021 Society of Chemical Industry.

Iron-Catalyzed Dearomatization of Biaryl Ynones with Aldehydes via Double C-H Functionalization in Eco-Benign Solvents: Highly Atom-Economical Synthesis of Acylated Spiro[5.5]trienones.

The multiple C-H bonds of biaryl ynones render the 6-exo-trig regioselective C-H activation dearomatization to spiro[5.5]trienones challenging since the competing reactions of C-H bonds on Ar1 or the ortho-C-H bonds on Ar3 may result in 5-exo-trig cyclization to indenones or 6-exo-trig ortho-dearomatization, respectively. We here report an unprecendented dearomatization of biaryl ynones with aldehydes via double C-H functionalization where a regiospecific remote unactivated para-C-H functionalization of biaryl ynones efficiently furnishes acylated spiro[5.5]trienones. This cascade cyclization features a green catalyst and solvent and high atom- and step-economy.

Intracellular uptake of agents that block the hERG channel can confound the assessment of QT interval prolongation and arrhythmic risk.

BACKGROUND: Oliceridine is a biased ligand at the µ-opioid receptor recently approved for the treatment of acute pain. In a thorough QT study, corrected QT (QTc) prolongation displayed peaks at 2.5 and 60 minutes after a supratherapeutic dose. The mean plasma concentration peaked at 5 minutes, declining rapidly thereafter. OBJECTIVE: The purpose of this study was to examine the basis for the delayed effect of oliceridine to prolong the QTc interval. METHODS: Repolarization parameters and tissue accumulation of oliceridine were evaluated in rabbit left ventricular wedge preparations over a period of 5 hours. The effects of oliceridine on ion channel currents were evaluated in human embryonic kidney and Chinese hamster ovary cells. Quinidine was used as a control. RESULTS: Oliceridine and quinidine produced a progressive prolongation of the QTc interval and action potential duration over a period of 5 hours, paralleling slow progressive tissue uptake of the drugs. Oliceridine caused modest prolongation of these parameters, whereas quinidine produced a prominent prolongation of action potential duration and QTc interval as well as development of early afterdepolarization (after 2 hours), resulting in a high torsades de pointes score. The 50% inhibitory concentration values for the oliceridine inhibition of the rapidly activating delayed rectifier current (human ether a-go-go current) and late sodium channel current were 2.2 and 3.45 µM when assessed after traditional acute exposure but much lower after 3 hours of drug exposure. CONCLUSION: Our findings suggest that a gradual increase of intracellular access of drugs to the hERG channels as a result of their intracellular uptake and accumulation can significantly delay effects on repolarization, thus confounding the assessment of QT interval prolongation and arrhythmic risk when studied acutely. The multi-ion channel effects of oliceridine, late sodium channel current inhibition in particular, point to a low risk of devloping torsades de pointes.

Cost-effectiveness and cost-benefit analysis of oliceridine in the treatment of acute pain.

Aim: Oliceridine, a new class of µ-opioid receptor agonist, is selective for G-protein signaling (analgesia) with limited recruitment of ß-arrestin (associated with adverse outcomes) and may provide a cost-effective alternative versus conventional opioid morphine for postoperative pain. Patients & methods: Using a decision tree with a 24-h time horizon, we calculated costs for medication and management of three most common adverse events (AEs; oxygen saturation <90%, vomiting and somnolence) following postoperative oliceridine or morphine use. Results: Using oliceridine, the cost for managing AEs was US$528,424 versus $852,429 for morphine, with a net cost savings of $324,005. Conclusion: Oliceridine has a favorable overall impact on the total cost of postoperative care compared with the use of the conventional opioid morphine.

Lay abstract Oliceridine, a new class of opioid pain medication, given in a vein, is a unique medication in that it provides pain relief comparable to morphine and may have less costly side effects. It is given in a hospital or surgery center for the treatment of postoperative pain and can save money compared with other opioid pain medicines due to fewer side effects. An economic model was developed to compare morphine to oliceridine for common side effects and pain relief following surgery. Oliceridine use resulted in a cost saving (US$324,005; 2020 US dollars) when compared with morphine.

Molecular docking and toxicity assessment of spirodiclofen: protective role of lycopene.

In this study, toxic effects of spirodiclofen and protective role of lycopene against toxic effects were investigated by using physiological, cytogenetic, anatomical, and biochemical parameters. Allium cepa L. bulbs were used as test material. The bulbs were divided into six groups as one control and five application groups. Bulb in the control group was germinated with tap water, and in treatment groups, 20-mg L-1 dose of spirodiclofen 215- and 430-mg L-1 doses of lycopene were applied. Spirodiclofen application caused a decrease in physiological parameters such as germination percentage, root length, and weight increase. Spirodiclofen administration caused a decrease in the percentage of mitotic index (MI) and an increase in DNA fragmentation, micronucleus (MN), and chromosomal aberration (CA) frequency. Spirodiclofen application caused an increase in the level of the oxidant compound malondialdehyde (MDA), changes in the level of antioxidant enzymes, and disruption of the oxidant/antioxidant balance in the cell. Molecular interactions between spirodiclofen and antioxidant enzymes were determined by molecular docking analysis. In addition to physiological, biochemical, and genetic abnormalities, spirodiclofen also caused deformations in the anatomy of the A. cepa root tip meristematic cells. Lycopene treatment showed a protective effect by suppressing the toxic effects of spirodiclofen, causing a significant improvement in the values of selected physiological, cytogenetic, anatomical, and biochemical parameters. As a result, spirodiclofen insecticide caused toxic effects on various parameters in A. cepa, which is a eukaryotic model organism. In order to elucidate the toxicity mechanism, each parameter is associated with each other. Molecular docking method has revealed the effects of spirodiclofen on antioxidant enzymes. Lycopene application together with spirodiclofen resulted in the regression of all toxic effects and improvement in the root tissue. This result shows that lycopene has a strong protective property against spirodiclofen toxicity.

Dissipation kinetics and dietary risk assessment of spiromesifen on major summer vegetables using good agricultural practices.

Dissipation kinetics and dietary risk assessment of spiromesifen is worked out on four summer vegetables, viz. okra, chilli, capsicum and brinjal (eggplant or aubergine) during March-April 2015 at the experimental farm of the Department of Entomology, Dr. Yashwant Singh Parmar University of Horticulture and Forestry Nauni, Solan using good agricultutral practices. Two foliar applications of spiromesifen @ 144.0 g.a.i./ha each were given at 10 days interval with a knapsack sprayer with the first application at the fruit initiation stage. Sample were collected up to 15 days after pesticide application and processed using a modified QuEChERS method, which was validated by doing recovery studies having recovery range and RSD within established guidelines of SANCO. Estimation of spiromesifen residues was conducted on GC-MS. The initial deposits after spraying of spiromesifen on okra, capsicum, chilli and brinjal fruit after 2 h of treatment were 1.327, 0.727, 0.800 and 0.738 mg/kg, respectively. The residues persisted up to 7 days and further dissipated and declined below the limit of quantification of <0.025 mg/kg at 10 days after treatment in all of the crops under investigation. Dissipation of spiromesifen followed first-order kinetics. The spiromesifen residues dissipated to half in 1.6, 1.8, 1.9 and 1.7 days with the suggested safe waiting period of 8.9, 5.2, 6.0 and 7.0 in the respective crops. The hazard quotient was <1 and theoretical maximum dietary intake was less than the maximum permissible intake, which was less than the maximum residue limit in all of the vegetable crops under investigation.

Colorimetric detection and bio-magnification of bisphenol A in fish organs and water sources using 3',6'-bis(diethylamino)-2- ((3,4,5trimethyl benzylidene) amino) spiro [isoindoline -1,9'-xanthen ]-3-one (BTSIXO)-Fe3+ ion conjugate.

Current study is focusing mainly on the development of simple, novel, and cost-effective optical sensor to detect and quantify Bisphenol A (BPA) contamination. We designed a very selective and sensitive colorimetric sensor using synthesized 3', 6'- bis(diethylamino) -2- ((3,4,5 trimethyl benzylidene) amino)spiro [isoindoline-1,9'-xanthen] -3-one (BTSIXO) conjugated with Fe3+-ions via very simple eco- friendly synthetic protocol. The sensor has an excellent wide detection range for BPA from 0.1 to 150 ppm with LODs of 0.02 ppm. Finally, the applicability of the sensor was demonstrated in fish samples especially in the organs of Oreochromis mossambicus fingerlings and contaminated industrial water samples. The sensor was also applied for the quantification of BPA present drinking water stored in the plastic bottles. The developed sensor has shown a good agreement and accuracy when compared with ESI-Mass techniques.

Medical, Political, and Economic Considerations for the Use of MAC for Endoscopic Sedation: Big Price, Little Justification?

The last few decades of gastrointestinal (GI) endoscopy have seen phenomenal growth. In many aspects, GI endoscopy has led the field of nonsurgical interventional medicine. In many aspects, this growth is facilitated by advancements in sedation-both drugs and techniques. Unfortunately, the topic of GI endoscopy sedation is also mired in many controversies, mainly emanating from the cost of anesthesia providers. While no one debates their role in the majority of advanced endoscopic procedures, the practice of universal propofol sedation in the USA, delivered by anesthesia providers, needs a closer look. In this review, medical, political, and economic considerations of this important topic are discussed in a very frank and honest way. While such ubiquitous propofol use has increased satisfaction of both patients and gastroenterologists, there is little justification. More importantly, going by the evidence, there is even less justification for the mandated anesthesia providers use for such delivery. Unfortunately, the FDA could not be convinced otherwise. The new drug fospropofol met the same fate. Approval of SEDASYS®, the first computer-assisted personalized sedation system, was a step in the right direction, nevertheless an insufficient step that failed to takeoff. As a result, in spite of years of research and efforts of many august societies, the logjam of balancing cost and justification of propofol sedation has continued. We hope that recent approval of remimazolam, a novel benzodiazepine, and potential approval of oliceridine, a novel short-acting opioid, might be able to contain the cost without compromising the quality of sedation.