Deletion of annexin 2 light chain p11 in nociceptors causes deficits in somatosensory coding and pain behavior

The S100 family protein p11 (S100A10, annexin 2 light chain) is involved in the trafficking of the voltage-gated sodium channel Na(V)1.8, TWIK-related acid-sensitive K+ channel (TASK-1), the ligand-gated ion channels acid-sensing ion channel 1a (ASIC1a) and transient receptor potential vanilloid 5/6 (TRPV5/V6), as well as 5-hydroxytryptamine receptor 1B (5-HT1B), a G-protein-coupled receptor. To evaluate the role of p11 in peripheral pain pathways, we generated a loxP-flanked (floxed) p11 mouse and used the Cre-loxP recombinase system to delete p11 exclusively from nociceptive primary sensory neurons in mice. p11-null neurons showed deficits in the expression of NaV1.8, but not of annexin 2. Damage-sensing primary neurons from these animals show a reduced tetrodotoxin-resistant sodium current density, consistent with a loss of membrane-associated NaV1.8. Noxious coding in wide-dynamic-range neurons in the dorsal horn was markedly compromised. Acute pain behavior was attenuated in certain models, but no deficits in inflammatory pain were observed. A significant deficit in neuropathic pain behavior was also apparent in the conditional-null mice. These results confirm an important role for p11 in nociceptor function

First trimester screening of serum soluble fms-like tyrosine kinase-1 and placental growth factor predicting hypertensive disorders of pregnancy

AbstractObjectiveTo assess the accuracy of first trimester soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in predicting pregnancy hypertension and pre-eclampsia; and compare with the accuracy of routinely collected maternal and clinical risk factors.Study designIn this population-based cohort study, serum sFlt-1 and PlGF levels were measured in first trimester in 2,681 women with singleton pregnancies in New South Wales, Australia.Main outcome measuresPrediction of pregnancy hypertension and pre-eclampsia.ResultsThere were 213 (7.9%) women with pregnancy hypertension, including 68 (2.5%) with pre-eclampsia. The area under the curve (AUC) for both sFlt-1 and PlGF was not different from chance, but combined was 0.55 (P=0.005). Parity and previous diagnosed hypertension had better predictive accuracy than serum biomarkers (AUC=0.64, P<0.001) and the predictive accuracy for all maternal and clinical information was fair (AUC=0.70, P<0.001 for pregnancy hypertension and AUC=0.74, P<0.001 for pre-eclampsia). Adding sFlt-1 and PlGF to maternal risk factors did not improve the ability of the models to predict pregnancy hypertension or pre-eclampsia.ConclusionsMaternal first trimester serum concentrations of sFlt-1 and PlGF do not predict hypertensive disorders in pregnancy any better than routinely collected clinical and maternal risk factor information. Screening for sFlt-1 and PlGF levels in early pregnancy would not identify those pregnancies at-risk

Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes

Objective: To assess Ang-1, Ang-2 and the Ang-1/Ang-2 ratio levels in the first trimester of pregnancy, their association with adverse pregnancy outcomes; and their predictive accuracy. Study Design: This cohort study measured serum Ang-1 and Ang-2 levels in 4,785 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum biomarkers with subsequent adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, miscarriage >10 weeks and stillbirth). Results: Median (interquartile range) levels for Ang-1, Ang-2 and the Ang-1/Ang-2 ratio for the total population were 19.6 ng/ml (13.6-26.4), 15.5 ng/ml (10.3-22.7) and 1.21 (0.83-1.73), respectively. Maternal age, weight, country of birth and socio-economic status significantly affected Ang-1, Ang-2 and the Ang-1/Ang-2 ratio levels. After adjusting for maternal and clinical risk factors, women with low Ang-2 levels (90th centile) had increased risk of developing most adverse pregnancy outcomes. Compared to the Ang-1/Ang-2 ratio alone, maternal and clinical risk factors had better predictive accuracy for most adverse pregnancy outcomes. The exception was miscarriage [Ang-1/Ang-2 ratio area under ROC curve (AUC) =0.70; maternal risk factors AUC =0.58]. Overall, adding the Ang-1/Ang-2 ratio to maternal risk factors did not improve the ability of the models to predict adverse pregnancy outcomes. Conclusions: Our findings suggest that the Ang-1/Ang-2 ratio in first trimester is associated with most adverse pregnancy outcomes, but do not predict outcomes any better than clinical and maternal risk factor information.Australian National Health and Medical Research Council (NHMRC) Project Grant (#632653)

First trimester screening of serum soluble fms-like tyrosine kinase-1 and placental growth factor predicting hypertensive disorders of pregnancy

AbstractObjectiveTo assess the accuracy of first trimester soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in predicting pregnancy hypertension and pre-eclampsia; and compare with the accuracy of routinely collected maternal and clinical risk factors.Study designIn this population-based cohort study, serum sFlt-1 and PlGF levels were measured in first trimester in 2,681 women with singleton pregnancies in New South Wales, Australia.Main outcome measuresPrediction of pregnancy hypertension and pre-eclampsia.ResultsThere were 213 (7.9%) women with pregnancy hypertension, including 68 (2.5%) with pre-eclampsia. The area under the curve (AUC) for both sFlt-1 and PlGF was not different from chance, but combined was 0.55 (P=0.005). Parity and previous diagnosed hypertension had better predictive accuracy than serum biomarkers (AUC=0.64, P<0.001) and the predictive accuracy for all maternal and clinical information was fair (AUC=0.70, P<0.001 for pregnancy hypertension and AUC=0.74, P<0.001 for pre-eclampsia). Adding sFlt-1 and PlGF to maternal risk factors did not improve the ability of the models to predict pregnancy hypertension or pre-eclampsia.ConclusionsMaternal first trimester serum concentrations of sFlt-1 and PlGF do not predict hypertensive disorders in pregnancy any better than routinely collected clinical and maternal risk factor information. Screening for sFlt-1 and PlGF levels in early pregnancy would not identify those pregnancies at-risk

Excited states in the twisted XXZ spin chain

We compute the finite size spectrum for the spin 1/2 XXZ chain with twisted boundary conditions, for anisotropy in the regime $0< \gamma <\pi/2$, and arbitrary twist $\theta$. The string hypothesis is employed for treating complex excitations. The Bethe Ansatz equtions are solved within a coupled non-linear integral equation approach, with one equation for each type of string. The root-of-unity quantum group invariant periodic chain reduces to the XXZ_1/2 chain with a set of twist boundary conditions ($\pi/\gamma\in Z$, $\theta$ an integer multiple of $\gamma$). For this model, the restricted Hilbert space corresponds to an unitary conformal field theory, and we recover all primary states in the Kac table in terms of states with specific twist and strings.Comment: 16 pages, Latex; added discussion on quantum group invariance and arbitrary magnon numbe

Inverting Time-Dependent Harmonic Oscillator Potential by a Unitary Transformation and a New Class of Exactly Solvable Oscillators

A time-dependent unitary (canonical) transformation is found which maps the Hamiltonian for a harmonic oscillator with time-dependent real mass and real frequency to that of a generalized harmonic oscillator with time-dependent real mass and imaginary frequency. The latter may be reduced to an ordinary harmonic oscillator by means of another unitary (canonical) transformation. A simple analysis of the resulting system leads to the identification of a previously unknown class of exactly solvable time-dependent oscillators. Furthermore, it is shown how one can apply these results to establish a canonical equivalence between some real and imaginary frequency oscillators. In particular it is shown that a harmonic oscillator whose frequency is constant and whose mass grows linearly in time is canonically equivalent with an oscillator whose frequency changes from being real to imaginary and vice versa repeatedly.Comment: 7 pages, 1 figure include

Maternal first trimester serum levels of free-beta human chorionic gonadotropin and male genital

Are maternal first trimester levels of serum free-beta hCG associated with the development of hypospadias or undescended testis (UDT) in boys? Overall, first trimester maternal levels of serum free-beta hCG are not associated with hypospadias or UDT. However, elevated levels were found in severe phenotypes (proximal hypospadias and bilateral UDT) suggesting an altered pathway of hormonal release in early pregnancy