A 3-Species Aquatic Community Model for Ecological Risk Assessment Using Basic Ecotoxicity Data.

A simplified ecosystem model, the Aquatic Tritrophic Ecological Risk Assessment Model (A-TERAM), for the ecological risk assessment of chemicals is presented. The A-TERAM comprises a linear grazer food chain with 3 trophic levels (the algae-Daphnia-fish system). The model simulates the seasonal patterns of abundance at each level observed in the field, and it translates the direct toxic effects of chemicals on algae or Daphnia to implications for fish via ecological interactions; thus, the A-TERAM evaluates ecological risk in terms of the annual population growth rate of fish. The model also incorporates toxicokinetics for fish. The minimum input data required for the A-TERAM are basic ecotoxicity endpoints (algal growth inhibition median effect concentration [EC50] or no-observed effect concentration, Daphnia immobility EC50, and fish acute mortality median lethal concentration); however, additional ecotoxicity data (Daphnia reproduction test, fish early life test, and fish reproduction test) are also relevant for improving simulations. Comparisons made across 496 chemicals (255 nonagricultural chemicals and 241 agrochemicals) indicated that the A-TERAM, in comparison with the conventional predicted-effect concentration/predicted-no-effect concentration method, tended to evaluate higher risk to chemicals that are highly bioaccumulative and toxic to fish by 2 orders of magnitude at the largest but lower or comparable risk to chemicals that are toxic only to algae or Daphnia. Environ Toxicol Chem 2020;39:1086-1100. © 2020 SETAC.

[Aspiration pneumonia in elderly stroke patients in a convalescent rehabilitation ward: Risk factors and effects on recovery after stroke].

AIM: To clarify risk factors for aspiration pneumonia and the effects of aspiration pneumonia on the recovery after stroke in elderly stroke patients in a convalescent rehabilitation ward. METHODS: We conducted a retrospective study of 463 stroke patients with dysphagia who were ≥65 years of age (mean age, 80.2±8.1 years) who were admitted to our convalescent rehabilitation ward. Information was obtained from medical charts. A multivariate analysis was performed to clarify risk factors for aspiration pneumonia and the association between aspiration pneumonia and increased functional oral intake scale and functional independence measure motor scores. For the increase in functional independence measure motor score, values of ≥16 points and ≤15 points were coded as 1 and 0, respectively. RESULTS: Aspiration pneumonia developed in 52 patients. The multivariate analysis revealed that male sex (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.59-5.95, p<0.001), geriatric nutritional risk index (OR for one unit increase 0.94, 95% CI 0.90-0.97, p<0.001) and tube feeding (OR 3.89, 95% CI 1.71-8.83, p=0.001) on admission were significant predictors of aspiration pneumonia. Aspiration pneumonia was associated with increased functional oral intake scale scores (OR 0.29, 95% CI 0.12-0.66, P=0.003) and increased functional independence measure motor scores (OR 0.23, 95% CI 0.09-0.55, P=0.001). CONCLUSIONS: Male sex, undernutrition and tube feeding on admission are risk factors for aspiration pneumonia. Aspiration pneumonia is suggested to be associated with recovery of the oral intake of food and activities of daily living.

Relative robustness of NOEC and ECx against large uncertainties in data.

The relative ability of the NOEC (no-observed-effect concentration) and ECx (the effect concentration corresponding to x-percent response) to determine benchmark toxicant concentrations, which are expected to ensure environmental safety, when there are large uncertainties in data was investigated with Monte Carlo simulations. We assumed a hypothetical true concentration-response function, and examined how random fluctuations of responses around the true responses affected the NOEC and ECx values. For assessment of the relative performances of these endpoints, we adopted two criteria: how large uncertainties were allowed for the minimum requirement for safety to be met, and the probability with which the estimated endpoints exceeded the minimum requirement for safety. The results of simulations indicated that, when there were small uncertainties in the data, performance of the NOEC was comparable with or slightly better than the ECx (EC5 and EC10) in providing benchmark concentrations that satisfied the minimum requirement for safety. With larger random variation of data (the coefficient of variation in responses between replicates within treatments or in the control was noticeably larger than 10 percent), the NOEC performed considerably worse than the ECx in terms of the frequency of simulated runs in which the endpoints exceeded the minimum requirement of safety. We conclude that the NOEC is as relevant as the ECx for risk assessment of chemicals under limited situations.

Estimation of population-level effect of the endocrine disruptor pyriproxyfen in Daphnia magna by using changes in sex ratio and reproductive output.

Here we developed an analytical means of estimating population-level effects of endocrine disruptors on Daphnia magna. Our approach was based on the fact that the endocrine-disrupting juvenile hormone analogs induce the production of male neonates if they are exposed to the analogs during a particular period in their prenatal development; the method also assumed that the abnormal production of male neonates in the sake of production of female neonates reduces population growth. We constructed a linear toxicodynamics model to elucidate the period in which D. magna neonates are sensitive to exposure to the analog and also the probability of an individual neonate changing sex under specific exposure concentrations. The proposed model was applied to D. magna reproduction test data obtained under time-varying exposure to pyriproxyfen to derive the maximum-likelihood estimates and the posterior distributions of the model parameters. To quantitatively assess the ecological risk at the population level, we conducted a population dynamics simulation under two time-varying exposure scenarios (i.e., constant or pulsed exposure) by using an age-structured population model. When the change in sex ratio was based on the time-weighted average concentration during the period of sensitivity, change in sex ratio caused approximately equivalent population-level effects as did reproductive inhibition (i.e., reduction in the total number of neonates per female parent) regardless of the exposure scenario. In contrast, when change in sex ratio was based on maximum concentration during the sensitive period, change in sex ratio caused only half the population-level effects as did reproductive inhibition under constant exposure, whereas it caused a much larger population-level effect than did reproductive inhibition under pulsed exposure.

cGMP-dependent relaxation of smooth muscle is coupled with the change in the phosphorylation of myosin phosphatase.

Nitric oxide/cGMP pathway induces vasodilatation, yet the underlying mechanism is obscure. In the present study, we studied the mechanism of cGMP-induced relaxation of the smooth muscle contractile apparatus using permeabilized rabbit femoral arterial smooth muscle. 8-Br-cGMP-induced relaxation was accompanied with a decrease in myosin light chain (MLC) phosphorylation. MLC phosphatase (MLCP) activity, once decreased by agonist-stimulation, recovered to the resting level on addition of 8-Br-cGMP. Because MLCP activity is regulated by the phosphorylation of a MLCP-specific inhibitor, CPI17 at Thr38 and MBS (myosin binding subunit of MLCP) at Thr696, we examined the effect of 8-Br-cGMP on the phosphorylation of these MLCP modulators. Whereas CPI17 phosphorylation was unchanged after addition of 8-Br-cGMP, MBS phosphorylation at Thr696 was significantly decreased by 8-Br-cGMP. We found that 8-Br-cGMP markedly increased MBS phosphorylation at Ser695 in the fiber pretreated with phenylephrine. MBS phosphorylation of Thr696 phosphorylated MBS at Ser695 partially resumed MLCP activity inhibited by Thr696 phosphorylation. Whereas Ser695 phosphorylation was markedly increased, the extent of diphosphorylated MBS at Ser695 and Thr696 in fibers was unchanged after cGMP-stimulation. We found that MBS phosphatase activity in arteries for both diphosphorylated MBS and monophosphorylated MBS at Thr696 significantly increased by 8-Br-cGMP, whereas MBS kinase activity was unchanged. These results suggest that the phosphorylation at Ser640 induced by cGMP shifted the equilibrium of the Thr641 phosphorylation toward dephosphorylation, thus increasing MLCP activity. This results in the decrease in MLC phosphorylation and smooth muscle relaxation.