Disrupting Circadian Homeostasis of Sympathetic Signaling Promotes Tumor Development in Mice

and why disruption of circadian rhythm may lead to tumorigenesis. oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice. is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor

Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study.

BACKGROUND: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors. OBJECTIVE: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality. STUDY DESIGN: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions. RESULTS: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios. CONCLUSION: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19

Drop motion, deformation, and cyclic motion in a non-uniform electric field in the viscous limit

Drop motion and deformation of a conducting drop in a perfect (or leaky) dielectric fluid and a leaky dielectric drop in a leaky dielectric fluid, in a non-uniform electric field is presented. The investigated non-uniform electrode configuration is of the pin-plate type. Systematic experiments and comparison with existing analytical models is carried out. The main results are summarized as follows: (i) The dielectrophoretic motion of a conducting drop in a non-uniform electric field is explained reasonably well assuming a spherical drop, although deviations are observed at large deformations. Thus dielectrophoretic motion shows a weak shape dependence. (ii) The deformation of a conducting drop in a non-uniform electric field has comparable contributions from the uniform and the non-uniform components of the applied field. (iii) The leaky dielectric nature of the medium results in three different states for a conducting drop (a) no movement, (b) near electrode cyclic motion, and (c) cyclic motion between the electrodes. The frequency of cyclic motion decreases with electric field for near electrode motion. On the contrary it increases with the applied field for electrode-electrode cyclic motion. The leaky dielectric system showing positive dielectrophoresis leads to the drop getting attached to the pin electrode causing emulsification at large field. A leaky dielectric drop suspended in a dielectric, system exhibiting negative dielectrophoresis shows oblate deformation which is augmented by the plate-drop hydrodynamic interaction. (C) 2013 AIP Publishing LLC

Stability of a charged drop near a conductor wall

The effect of conductor boundaries on the deformation and stability of a charged drop is presented. The motivation for such a study is the occurrence of a charged conductor drop near a conductor wall in experiments (Millikan-like set-up in studies on Rayleigh break-up) and applications (such as electrospraying, ink-jet printing and ion mass spectroscopy). In the present work, analytical (linear stability analysis (LSA)) and numerical methods (boundary element method (BEM)) are used to understand the instability. Two kinds of boundaries are studied: a spherical, conducting, grounded enclosure (similar to a spherical capacitor) and a planar conducting wall. The LSA of a charged drop placed at the center of a spherical cavity shows that the Rayleigh critical charge (corresponding to the most unstable l = 2 Legendre mode) is reduced as the non-dimensional distance (d) over cap = b-a/a decreases, where a and b are the radii of the drop and spherical cavity, respectively. The critical charge is independent of the assumptions of constant charge or constant potential conditions. The trans-critical bifurcation diagram, constructed using BEM, shows that the prolate shapes are subcritically unstable over a much wider range of charge as (d) over cap decreases. The study is then extended to the stability of a charged conductor drop near a flat conductor wall. Analytical theory for this case is difficult and the stability as well as the bifurcation diagram are constructed using BEM. Moreover, the induced charges in the conductor wall lead to attraction of the drop to the wall, thereby making it difficult to conduct a systematic analysis. The drop is therefore assumed to be held at its position by an external force such as the electric field. The case when the applied field is much smaller than the field due to inherent charge on the drop (a(3)rho g/3e(0)psi(2) << 1) is considered. The wall breaks the fore-aft symmetry in the problem, and equilibrium, predominantly prolate shapes corresponding to the legendre mode, l = 2, are observed. The deformation increases with increasing charge on the drop. The breakup of the prolate equilibrium shapes is independent of the legendre modes of the initial perturbations. The prolate perturbations are subcritically unstable. Since the equilibrium prolate shapes cannot continuously exchange instability with equilibrium oblate shapes, an imperfect transcritical bifurcation is observed. A variety of highly deformed equilibrium oblate shapes are predicted by the BEM calculations

Electrocoalescence of a drop pair

The interaction and coalescence of a freely suspended drop pair, aligned in a uniform DC electric field is investigated using experiments, analytical theory, and numerical calculations (boundary element method (BEM)). The systems considered are a pair of perfect conductor drops in a perfect dielectric fluid and a pair of leaky dielectric drops suspended in another leaky dielectric fluid. The applied electric field induces a dipole in the drops that form a pair, leading to their approach and subsequent merger. The study focuses on the drop approach and the film drainage stages of drop-drop electrocoalescence. The shapes and motion predicted using BEM are in good agreement with the experimental results and analytical theory. (C) 2015 AIP Publishing LLC