An Observational Study on the Pharmacokinetics of Oseltamivir in Lactating Influenza Patients.

Influenza infection may lead to serious complications in the postpartum period, therefore, oseltamivir treatment in these patients and their breastfed infants is of great importance. However, the pharmacokinetics of oseltamivir in postpartum lactating women with acute influenza infection, and the consequent infant exposure to oseltamivir are still unknown, and these data would help in assessing risk and the need for dose adjustment in breastfed infants. Six lactating women with influenza-like symptoms, at a standard dose of 75 mg oral oseltamivir twice daily for 5 days, were recruited in this phase IV clinical study during the 2011/2012 H1N1 pandemic seasons. Breast milk/colostrum and venous blood samples were taken at multiple timepoints, maternal urine samples were obtained from total output within the 12-hour observational period following the seventh dose of oseltamivir. Oseltamivir phosphate (OP) reached a maximum 69.5 ± 29.4 ng/mL concentration in breast milk, higher than that found in the plasma, and showed elimination within ~ 8 hours. Oseltamivir carboxylate (active metabolite of OP) showed a lower, nearly steady-state concentration in breast milk during the observational period (maximum plasma concentration (Cmax ) = 38.4 ± 12.9 ng/mL). Based on estimated daily milk consumption of exclusively breastfed infants, their calculated daily exposure is < 0.1% of the infant dose of oseltamivir for treatment of influenza as per marketing authorization. Here, we provide the first maternal breast milk pharmacokinetic data for oral multiple-dose oseltamivir in lactating patients with influenza and showed that its concentration in the breast milk is not sufficient to reach a therapeutic dose for breastfed infants.

Heat transfer augmentation in nanofluids via nanofins.

Theoretical results derived in this article are combined with experimental data to conclude that, while there is no improvement in the effective thermal conductivity of nanofluids beyond the Maxwell's effective medium theory (J.C. Maxwell, Treatise on Electricity and Magnetism, 1891), there is substantial heat transfer augmentation via nanofins. The latter are formed as attachments on the hot wire surface by yet an unknown mechanism, which could be related to electrophoresis, but there is no conclusive evidence yet to prove this proposed mechanism.

On the distinction between lag and delay in population growth.

The analysis and results presented in this paper provide conclusive evidence to distinguish between the delay effect and the lag as two biologically distinct phenomena. It therefore dispels the incorrect notion that delay effects represented by delay differential equations are the biological reason behind the lag phase in microorganism growth. The resulting consequence so far is that the only other reason for the lag phase is the existence of unstable stationary states. The latter are a result of accounting for the microbial metabolic mass transfer in the population growth process.

Continuous combined hormone replacement therapy relieves climacteric symptoms and improves health-related quality of life in early postmenopausal women.

OBJECTIVE: Hormone replacement therapy (HRT) relieves menopausal symptoms but its effect on health related quality of life (HRQoL) is uncertain. The aim of this study was to assess the effect of three dose regimens of continuous combined HRT, consisting of estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) on HRQoL in early postmenopausal women (last menstrual period 1-3 years before study entry). STUDY DESIGN: This was a 52-week, randomized, double-blind, multinational study comparing E2V (1 mg or 2 mg) plus MPA (2.5 mg or 5 mg) in different dose combinations. The intention-to-treat population comprised 459 women (average age 51.5 years). MAIN OUTCOME MEASURES: HRQoL was assessed by the Women's Health Questionnaire (WHQ), the 15D Questionnaire and a visual analogue scale (VAS). RESULTS: There were improvements on eight of the nine domains of the WHQ with all dose regimens during the first 12 weeks (P<0.0001) and an improvement in the remaining domain (menstrual symptoms) with the lower-dose regimens (P<0.05). These initial improvements in HRQoL were then maintained or augmented over the remainder of the study (P<0.0001 for change from baseline at 52 weeks for all domains and dose regimens). Mean 15D total score had improved meaningfully and significantly by 12 weeks (P<0.0001 versus baseline) in all treatment groups and this improvement was maintained thereafter. This improvement in 15D total score was most marked among previous non-users of HRT (P<0.05 versus previous users). VAS scores recorded significant (P<0.05) reductions in hot flushes, sweating and sleep disturbances in all groups after week 1 and highly significant (P<0.0001) relief of all climacteric symptoms at week 52. CONCLUSION: Continuous combined HRT was associated with pronounced improvement of vasomotor symptoms and HRQoL in this population of early postmenopausal women.

Biological implications from an autonomous version of Baranyi and Roberts growth model.

An autonomous version of Baranyi and Roberts model (Int. J. Food Microbiology, 23, 1994, pp. 277-294) is developed and analyzed to reveal some subtle points, which are difficult to observe accurately from its equivalent non-autonomous form. In particular we are able to provide a meaningful interpretation to the "physiological state of the cells at inoculation", a parameter introduced by Baranyi and Roberts [Baranyi, J., Roberts, T. A., 1994. A dynamic approach to predicting bacterial growth in food. International Journal of Food Microbiology 23, 277-294] that has a profound impact on microbial growth but is not a direct measurable quantity. In addition, the analysis shows that the transient growth depends on the initial cell concentration and the initial growth rate, but is independent of "the history of the cells" and depends only indirectly (via the initial growth rate) on the previous (pre-inoculation) environment. The stationary solution is independent of the initial conditions. A new, more natural, and biologically meaningful formulation of LAG duration is being suggested in terms of initial conditions being in the neighborhood of one of the unstable stationary points revealed by this autonomous version of the model.

Predictive modeling of microorganisms: LAG and LIP in monotonic growth.

The variety of models that are currently being used in "Predictive Microbiology" or "Microbial Ecology" aiming at reproducing the growth curve of microorganisms motivates this study. It is widely agreed that no model can reproduce generically and consistently the "LAG Phase" of microorganism growth. To promote the objective of "predictive modeling", we present here a model that was derived from first biological and physical principles, which is shown to reproduce qualitatively as well as quantitatively all typical features captured experimentally in microorganism growth. In particular, this paper focuses on capturing and controlling of the "LAG Phase" a typical phase in microorganisms growth, at the initial growth stages, as well as the inflection point on the "ln curve" of the cell concentration, i.e. a Logarithmic Inflection Point referred here as "LIP". The proposed model also captures the Logistic Growth curve as a special case. Comparison of the solutions obtained from the proposed model with experimental data confirms its quantitative validity, as well as its ability to recover a wide range of qualitative features captured in experiments.