Prognostic and Mechanistic Potential of Progesterone Sulfates in Intrahepatic Cholestasis of Pregnancy and Pruritus Gravidarum

A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9-15 weeks of gestation and prior to symptom onset (group 1 cases/samples: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first-trimester samples all progesterone sulfates were significantly elevated in serum from low-risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5-dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high-risk population. Delineation of a progesterone sulfate-TGR5 pruritus axis identifies a therapeutic target for itch management in ICP

Vortex Lattice Melting in 2D Superconducting Networks and Films

We carry out MC studies of 2D superconducting networks, in an applied magnetic field, for square and honeycomb geometries. We consider both dilute systems (f=1/q) and systems near full frustration (f=1/2-1/q). For the dilute case (which models a film as q->infinity), we find two transitions: at T_c(f)~1/q there is a depinning transition from a pinned to a floating vortex lattice; at T_m(f)~constant the floating vortex lattice melts into an isotropic liquid. We analyze this melting according to the Kosterlitz- Thouless theory of dislocation mediated melting, and find that the melting is weakly first order. For the case near full frustration, the system can be described in terms of the density of defects in an otherwise fully frustrated vortex pattern. We find pinned solid, floating solid, and liquid defect phases, as well as a higher sharp transition corresponding to the disordering of the fully frustrated background.Comment: 55 pages, RevTex3.0, 25 figures (available by mail by contacting [email protected]

Does Prophylactic Vaccination Favour the Development of Poliomyelitis?

Seventy six cases of poliomyelitis have been admitted in St. Sophie Children's Hospital during the autumn of 1950. In seventeen of them there was a history of previous vaccination with mixed vaccine (pertussis‐tetanus‐diphtheria). The interval between vaccination and the appearance of paralysis was 2–14 days. In 75 % of the cases the paralysis occurred in the vaccinated limb. Copyright © 1953, Wiley Blackwell. All rights reserve

On the mean Euler characteristic and mean Betti's number of the Ising model with arbitrary spin

Blanchard P, Dobrovolny C, Gandolfo D, Ruiz J. On the mean Euler characteristic and mean Betti's number of the Ising model with arbitrary spin. J. Stat. Mech. 2006;2006(03): P03011