Data-Driven Estimation of the Impact of Diversions Due to In-Flight Medical Emergencies on Flight Delay and Aircraft Operating Costs.

INTRODUCTION: In-flight medical emergencies (IFMEs) average 1 of every 604 flights and are expected to increase as the population ages and air travel increases. Flight diversions, or the rerouting of a flight to an alternate destination, occur in 2 to 13% of IFME cases, but may or may not be necessary as determined after the fact. Estimating the effect of IFME diversions compared to nonmedical diversions can be expected to improve our understanding of their impact and allow for more appropriate decision making during IFMEs.METHODS: The current study matched multiple disparate datasets, including medical data, flight plan and track data, passenger statistics, and financial data. Chi-squared analysis and independent samples t-tests compared diversion delays and costs metrics between flights diverted for medical vs. nonmedical reasons. Data were restricted to domestic flights between 1/1/2018 and 6/30/2019.RESULTS: Over 70% of diverted flights recover (continue on to their intended destination after diverting); however, flights diverted due to IFMEs recover more often and more quickly than do flights diverted for nonmedical reasons. IFME diversions introduce less delay overall and cost less in terms of direct operating costs and passenger value of time (averaging around 38,000) than do flights diverted for nonmedical reasons.DISCUSSION: Flights diverted due to IFMEs appear to have less impact overall than do flights diverted for nonmedical reasons. However, the lack of information related to costs for nonrecovered flights and the decision factors involved during nonmedical diversions hinders our ability to offer further insights.Lewis BA, Gawron VJ, Esmaeilzadeh E, Mayer RH, Moreno-Hines F, Nerwich N, Alves PM. Data-driven estimation of the impact of diversions due to in-flight medical emergencies on flight delay and aircraft operating costs. Aerosp Med Hum Perform. 2021; 92(2):99105.

Structure-activity relationships of flavonoids as inhibitors of breast cancer resistance protein (BCRP).

Flavonoids are an interesting group of natural products ubiquitously present in human diet. Their consumption has been associated with various and differing beneficial health effects. However, several flavonoids have been reported to inhibit the breast cancer resistance protein (BCRP) encoded by the ABCG2 gene. Thus, the consumption of flavonoids with high inhibitory activity could change pharmacokinetics and drug levels of drugs that are BCRP substrates. In cancer patients receiving chemotherapy an increased intake of such flavonoids could lead to adverse effects. We investigated a structurally diverse set of flavonoids, including derivatives with a rare C-methylated structure that were isolated from plants used in traditional medicine. The flavones retusin and ayanin were found to be highly potent inhibitors of BCRP, showing only slightly less potency than Ko143, the most potent ABCG2 inhibitor known so far. The activity data were analyzed by 2D and 3D QSAR analyses and the results revealed the impact of the different substituents at the various positions of the flavonoid core on activity. Additionally, a lateral 2D QSAR analysis of data collected from the literature was performed aiming to derive more general information about the influence of distinct structural features on the inhibitory potency of flavonoids. The comparative QSAR analyses led to a consistent picture of the effects of the different substituents at various positions of the flavone backbone. The following structural features were found to contribute positively to BCRP inhibition: a hydroxyl group in position 5, double bond between position 2 and 3, and a methoxy group in position 3. The exchange of a 3-methoxy group by an OH-group acting also as a hydrogen bond donor, resulted in decrease in activity underlining the potential role of the hydrogen bond acceptor 3-OCH(3) for the interaction with BCRP.

Interaction of valerian extracts of different polarity with adenosine receptors: identification of isovaltrate as an inverse agonist at A1 receptors.

A series of extracts of valerian roots (Valeriana officinalis L.) was prepared with solvents of different polarity. Polar as well as nonpolar extracts were found to interact with adenosine A(1) receptors. While polar extracts activated A(1) receptors (partial agonistic activity), nonpolar extracts showed antagonistic or inverse agonistic activity at A(1) receptors, as demonstrated by GTPgammaS binding assays at human recombinant A(1) receptors stably expressed in Chinese hamster ovary (CHO) cells. Guided by radioligand binding assays, fractionation of a lipophilic petroleum ether:diethyl ether (1:1) extract led to the isolation of isovaltrate, which was characterized as a potent, highly efficacious inverse agonist at adenosine A(1) receptors (K(i) rat A(1): 2.05 microM). In experiments at rat brain slices measuring post-synaptic potentials (PSPs) in cortical neurons, isovaltrate at least partly reversed the reduction in the PSPs induced by the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA). Isovaltrate may serve as a new lead structure for the development of inverse agonists at adenosine A(1) receptors. The common use of hydrophilic, but not lipophilic valerian extracts as mild sleep-inducing agents is consistent with the opposite actions of hydrophilic and lipophilic extracts on adenosine receptors.

Sesquiterpene lactones are potent and irreversible inhibitors of the antibacterial target enzyme MurA.

We report the identification of the sesquiterpene lactones cnicin and cynaropicrin as potent, irreversible inhibitors of the bacterial enzyme MurA. They covalently bind to the thiol group of Cys115. Judging from the structure-activity relationships, we conclude that the unsaturated ester side chain of cynaropicrin and cnicin is of particular importance for the inhibition of MurA. These results provide evidence that MurA is a target protein of SLs with a probably high relevance for their known antibacterial effect.

Five biflavonoids from Calycopteris floribunda (Combretaceae).

The structures of five biflavonoids, 6"-demethoxyneocalycopterone (1), calyflorenone C (2), 6"-epi-calyflorenone B (3), 6"-epi-calyflorenone C (4) and calyflorenone D (5) from the green parts of Calycopteris floribunda were established by NMR and MS. Their NMR and chiroptical properties (CD, [alpha]20D ) were compared with those of the known C. f. biflavonoids 6-11. Compound 1 represents a calycopterone derivative, 2-5 have a calyflorenone skeleton. With regard to one chiral center (C-6"), 4 and 3 are the respective epimers of 2 and 11.