Dehydroepiandrosterone (DHEA) replacement decreases insulin resistance and lowers inflammatory cytokines in aging humans

Plasma dehydroepiandrosterone (DHEA) decreases ~80% between ages 25 and 75 yr. In a preliminary study, we found that 6 mo of DHEA replacement improved insulin action in elderly individuals. The purpose of the present larger, randomized double-blind study was to determine whether a longer period of DHEA replacement improves glucose tolerance. Fifty-seven men and 68 women aged 65 to 75 yr were randomly assigned to 50 mg DHEA or placebo once daily. Year one was a randomized, double blind trial. Year 2 was an open label continuation. DHEA replacement improved glucose tolerance in participants who had abnormal GT initially, reduced plasma triglycerides, and the inflammatory cytokines IL6 and TNFα

Assessing Photoreceptor Structure Associated with Ellipsoid Zone Disruptions Visualized with Optical Coherence Tomography

Purpose: To compare images of photoreceptor layer disruptions obtained with optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO) in a variety of pathologic states.Methods: Five subjects with photoreceptor ellipsoid zone disruption as per OCT and clinical diagnoses of closed-globe blunt ocular trauma (n = 2), macular telangiectasia type 2 (n = 1), blue-cone monochromacy (n = 1), or cone-rod dystrophy (n = 1) were included. Images were acquired within and around photoreceptor lesions using spectral domain OCT, confocal AOSLO, and split-detector AOSLO.Results: There were substantial differences in the extent and appearance of the photoreceptor mosaic as revealed by confocal AOSLO, split-detector AOSLO, and spectral domain OCT en face view of the ellipsoid zone.Conclusion: Clinically available spectral domain OCT, viewed en face or as B-scan, may lead to misinterpretation of photoreceptor anatomy in a variety of diseases and injuries. This was demonstrated using split-detector AOSLO to reveal substantial populations of photoreceptors in areas of no, low, or ambiguous ellipsoid zone reflectivity with en face OCT and confocal AOSLO. Although it is unclear if these photoreceptors are functional, their presence offers hope for therapeutic strategies aimed at preserving or restoring photoreceptor function

Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.

BackgroundSentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance.MethodsA total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept.ResultsA total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept.Conclusion[(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness and Oguchi Disease

Purpose To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. Design Prospective, observational case series. Methods We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. Results Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. Conclusions The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus

A Diffuse Metal-Poor Component of the Sagittarius Stream Revealed by the H3 Survey

The tidal disruption of the Sagittarius dwarf galaxy has generated a spectacular stream of stars wrapping around the entire Galaxy. We use data from $Gaia$ and the H3 Stellar Spectroscopic Survey to identify 823 high-quality Sagittarius members based on their angular momenta. The H3 Survey is largely unbiased in metallicity, and so our sample of Sagittarius members is similarly unbiased. Stream stars span a wide range in [Fe/H] from $-0.2$ to $\approx -3.0$, with a mean overall metallicity of $\langle$[Fe/H]$\rangle=-0.99$. We identify a strong metallicity-dependence to the kinematics of the stream members. At [Fe/H]$\gt -0.8$ nearly all members belong to the well-known cold ($\sigma_v \lt 20$ km/s) leading and trailing arms. At intermediate metallicities ($-1.9 \lt$[Fe/H]$\lt -0.8$) a significant population (24$\%$) emerges of stars that are kinematically offset from the cold arms. These stars also appear to have hotter kinematics. At the lowest metallicities ([Fe/H]$\lesssim-2$), the majority of stars (69$\%$) belong to this kinematically-offset diffuse population. Comparison to simulations suggests that the diffuse component was stripped from the Sagittarius progenitor at earlier epochs, and therefore resided at larger radius on average, compared to the colder metal-rich component. We speculate that this kinematically diffuse, low metallicity, population is the stellar halo of the Sagittarius progenitor system.Comment: 18 pages, 12 figures, 1 table. Submitted to Ap

Discovery of the Magellanic Stellar Stream Out to 100 Kiloparsecs

The Magellanic Stream (MS) - an enormous ribbon of gas spanning $140^\circ$ of the southern sky trailing the Magellanic Clouds - has been exquisitely mapped in the five decades since its discovery. However, despite concerted efforts, no stellar counterpart to the MS has been conclusively identified. This stellar stream would reveal the distance and 6D kinematics of the MS, constraining its formation and the past orbital history of the Clouds. We have been conducting a spectroscopic survey of the most distant and luminous red giant stars in the Galactic outskirts. From this dataset, we have discovered a prominent population of 13 stars matching the extreme angular momentum of the Clouds, spanning up to $100^\circ$ along the MS at distances of $60-120$ kpc. Furthermore, these kinemetically-selected stars lie along a [$\alpha$/Fe]-deficient track in chemical space from $-2.5 < \mathrm{[Fe/H]} < -0.5$, consistent with their formation in the Clouds themselves. We identify these stars as high-confidence members of the Magellanic Stellar Stream. Half of these stars are metal-rich and closely follow the gaseous MS, whereas the other half are more scattered and metal-poor. We argue that the metal-rich stream is the recently-formed tidal counterpart to the MS, and speculate that the metal-poor population was thrown out of the SMC outskirts during an earlier interaction between the Clouds. The Magellanic Stellar Stream provides a strong set of constraints - distances, 6D kinematics, and birth locations - that will guide future simulations towards unveiling the detailed history of the Clouds.Comment: 21 pages, 12 figures. Submitted to Ap

Anyonic interferometry and protected memories in atomic spin lattices

Strongly correlated quantum systems can exhibit exotic behavior called topological order which is characterized by non-local correlations that depend on the system topology. Such systems can exhibit remarkable phenomena such as quasi-particles with anyonic statistics and have been proposed as candidates for naturally fault-tolerant quantum computation. Despite these remarkable properties, anyons have never been observed in nature directly. Here we describe how to unambiguously detect and characterize such states in recently proposed spin lattice realizations using ultra-cold atoms or molecules trapped in an optical lattice. We propose an experimentally feasible technique to access non-local degrees of freedom by performing global operations on trapped spins mediated by an optical cavity mode. We show how to reliably read and write topologically protected quantum memory using an atomic or photonic qubit. Furthermore, our technique can be used to probe statistics and dynamics of anyonic excitations.Comment: 14 pages, 6 figure