Effects of Toremifene, a Selective Estrogen Receptor Modulator, on Spontaneous and StimulatedGHSecretion, IGF-I, and IGF-Binding Proteins in Healthy Elderly Subjects

Diabetes mellitus: pathophysiological changes and therap

Possibility of an ultra-precise optical clock using the 61S0→63P0o6 ^1S_0 \to 6 ^3P^o_0 transition in 171,173^{171, 173}Yb atoms held in an optical lattice

We report calculations designed to assess the ultimate precision of an atomic clock based on the 578 nm $6 ^1S_0 --> 6 ^3P^o_0$ transition in Yb atoms confined in an optical lattice trap. We find that this transition has a natural linewidth less than 10 mHz in the odd Yb isotopes, caused by hyperfine coupling. The shift in this transition due to the trapping light acting through the lowest order AC polarizability is found to become zero at the magic trap wavelength of about 752 nm. The effects of Rayleigh scattering, higher-order polarizabilities, vector polarizability, and hyperfine induced electronic magnetic moments can all be held below a mHz (about a part in 10^{18}), except in the case of the hyperpolarizability larger shifts due to nearly resonant terms cannot be ruled out without an accurate measurement of the magic wavelength.Comment: 4 pages, 1 figur

Supernova neutrino challenges

A principal `supernova neutrino challenge' is the computational difficulty of six-dimensional neutrino radiation hydrodynamics. The variety of resulting approximations has provoked a long history of uncertainty in the core-collapse supernova explosion mechanism, but recent work highlighting low-mode convection and a newly-recognized instability in spherical accretion shocks may signal (yet another) resolution. As part of its goal of elucidating the explosion mechanism, the Terascale Supernova Initiative is committed to meeting the full complexity of the computational challenge. The understanding of supernova neutrino emission gained in detailed simulations provides a potential basis for learning about two major remaining unknowns in neutrino flavor mixing: the value of the mixing angle $\theta_{13}$, and distinguishing between ``normal'' and ``inverted'' mass hierarchies.Comment: 6 pages. Contribution to the proceedings of NOW2004, Conca Specchiulla (Otranto, Italy), September 11-17, 2004, to be published by Nucl. Phys. B (Proc. Suppl.), ed. P. Bernardini, G.L. Fogli, and E. Lis

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Modulating Effects of Progesterone on Spontaneous Nocturnal and Ghrelin-Induced GH Secretion in Postmenopausal Women

Background: Oral administration of estradiol (E-2) generally increases GH secretion in postmenopausal women. Oral administration of E-2 is associated with a decrease in IGF-1, whereas parenteral or transdermally administered E-2 may have no effect on GH. The effect of progesterone (P4) on GH secretion has rarely been studied. We hypothesized that moderately increased serum E-2 levels stimulate GH and that P4 modulates E-2-stimulated GH secretion.Study Design: Four parallel groups of randomly assigned postmenopausal women (n = 40). Treatments were saline placebo and oral placebo, saline placebo and oral micronized P4 (3 x 200 mg/d IM), E-2 (5 mg IM) and oral placebo, and E-2 IM and oral micronized P4. Outcome measures were overnight GH secretion (10 hours), stimulated (ghrelin, 0.3 mu g/kg IV bolus) GH secretion, and CT-estimated visceral fat.Results: Intramuscular E-2 administration did not alter nocturnal and ghrelin-stimulated GH secretion. Nocturnal GH secretion was not changed by P4 administration. However, P4 diminished ghrelin-stimulated pulsatile GH release with or without E-2 (average, 7.20 +/- 2.14 and 9.58 +/- 1.97 mu g/L/2 h, respectively; P = 0.045). Respective outcomes for mean GH concentrations and GH peak amplitudes were 0.97 +/- 0.31 and 1.52 mu g/L +/- 0.29 (P = 0.025) and 2.76 +/- 1.04 and 3.95 mu g/L +/- 0.90 (P = 0.031). Ghrelin-stimulated GH secretion correlated negatively with P4 concentration with or without correction for visceral fat area in the regression equation (R = 0.49, P = 0.04, beta = -0.040 +/- 0.016).Conclusions: Low-range physiological E-2 concentrations do not affect spontaneous or ghrelin-stimulated pulsatile GH secretion. Conversely, P4 inhibits ghrelin-stimulated GH secretion in a concentration-dependent fashion. The mechanistic aspects and physiological significance of natural P4's regulation of ghrelin-evoked GH secretion require further study.Diabetes mellitus: pathophysiological changes and therap