A non-invasive method for measuring preimplantation embryo physiology

Author Posting. © Cambridge University Press, 2000. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Zygote 8 (2000): 15-24, doi:10.1017/S0967199400000782.The physiology of the early embryo may be indicative of embryo vitality and therefore methods for non-invasively monitoring physiological parameters from embryos could improve preimplantation diagnoses. The self-referencing electrophysiological technique is capable of non-invasive measurement of the physiology of individual cells by monitoring the movement of ions and molecules between the cell and the surrounding media. Here we use this technique to monitor gradients of calcium, potassium, oxygen and hydrogen peroxide around individual mouse preimplantation embryos. The calcium-sensitive electrode in self-referencing mode identified a region of elevated calcium concentration ([similar]0.25 pmol) surrounding each embryo. The calcium gradient surrounding embryos was relatively steep, such that the region of elevated calcium extended into the medium only 4 [mu]m from the embryo. By contrast, using an oxygen-sensitive electrode an extensive gradient of reduced dissolved oxygen concentration was measured surrounding the embryo and extended tens of micrometres into the medium. A gradient of neither potassium nor hydrogen peroxide was observed around unperturbed embryos. We also demonstrate that monitoring the physiology of embryos using the self-referencing technique does not compromise their subsequent development. Blastocysts studied with the self-referencing technique implanted and developed to term at the same frequency as did unexamined, control embryos. Therefore, the self-referencing electrode provides a valuable non-invasive technique for studying the physiology and pathophysiology of individual embryos without hindering their subsequent development.A portion of this work was funded by an NIH R21 #RR 12718–02 to D.L.K. and P.J.S.S., KO81099 to D.L.K. and NIH P41 RR01395 to P.J.S.S

Assessing Local Health Department Performance in Diabetes Prevention and Control — North Carolina, 2005

Introduction: To improve the public health system's ability to prevent and control chronic diseases, we must first understand current practice and develop appropriate strategies for measuring performance. The objectives of this study were to measure capacity and performance of local health departments in diabetes prevention and control and to investigate characteristics associated with performance. Methods: In 2005, we conducted a cross-sectional mailed survey of all 85 North Carolina local health departments to assess capacity and performance in diabetes prevention and control based on the 10 Essential Public Health Services and adapted from the Local Public Health System Performance Assessment Instrument. We linked survey responses to county-level data, including data from a national survey of local health departments. Results: Local health departments reported a median of 0.05 full-time equivalent employees in diabetes prevention and 0.1 in control. Performance varied across the 10 Essential Services; activities most commonly reported included providing information to the public and to policy makers (76%), providing diabetes education (58%), and screening (74%). The mean score on a 10-point performance index was 3.5. Characteristics associated with performance were population size, health department size and accreditation status, and diabetes-specific external funding. Performance was not better in localities where the prevalence of diabetes was high or availability of primary care was low. Conclusion: Most North Carolina local health departments had limited capacity to conduct diabetes prevention or control programs in their communities. Diabetes is a major cause of illness and death, yet it is neglected in public health practice. These findings suggest opportunities to enhance local public health practice, particularly through targeted funding and technical assistance

The First Swift Ultra-Violet/Optical Telescope GRB Afterglow Catalog

We present the first Swift Ultra-Violet/Optical Telescope (UVOT) gamma-ray burst (GRB) afterglow catalog. The catalog contains data from over 64,000 independent UVOT image observations of 229 GRBs first detected by Swift, the High Energy Transient Explorer 2 (HETE2), the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL), and the Interplanetary Network (IPN). The catalog covers GRBs occurring during the period from 2005 Jan 17 to 2007 Jun 16 and includes ~86% of the bursts detected by the Swift Burst Alert Telescope (BAT). The catalog provides detailed burst positional, temporal, and photometric information extracted from each of the UVOT images. Positions for bursts detected at the 3-sigma-level are provided with a nominal accuracy, relative to the USNO-B1 catalog, of ~0.25 arcseconds. Photometry for each burst is given in three UV bands, three optical bands, and a 'white' or open filter. Upper limits for magnitudes are reported for sources detected below 3-sigma. General properties of the burst sample and light curves, including the filter-dependent temporal slopes, are also provided. The majority of the UVOT light curves, for bursts detected at the 3-sigma-level, can be fit by a single power-law, with a median temporal slope (alpha) of 0.96, beginning several hundred seconds after the burst trigger and ending at ~1x10^5 s. The median UVOT v-band (~5500 Angstroms) magnitude at 2000 s for a sample of "well" detected bursts is 18.02. The UVOT flux interpolated to 2000 s after the burst, shows relatively strong correlations with both the prompt Swift BAT fluence, and the Swift X-ray flux at 11 hours after the trigger.Comment: 60 pages, 17 figures, 8 tables, accepted for publication by the Astrophysical Journa

Arsenic as an Endocrine Disruptor: Arsenic Disrupts Retinoic Acid Receptor–and Thyroid Hormone Receptor–Mediated Gene Regulation and Thyroid Hormone–Mediated Amphibian Tail Metamorphosis

Background: Chronic exposure to excess arsenic in drinking water has been strongly associated with increased risks of multiple cancers, diabetes, heart disease, and reproductive and developmental problems in humans. We previously demonstrated that As, a potent endocrine disruptor at low, environmentally relevant levels, alters steroid signaling at the level of receptor-mediated gene regulation for all five steroid receptors. Objectives: The goal of this study was to determine whether As can also disrupt gene regulation via the retinoic acid (RA) receptor (RAR) and/or the thyroid hormone (TH) receptor (TR) and whether these effects are similar to previously observed effects on steroid regulation. Methods and results: Human embryonic NT2 or rat pituitary GH3 cells were treated with 0.01–5 μM sodium arsenite for 24 hr, with or without RA or TH, respectively, to examine effects of As on receptor-mediated gene transcription. At low, noncytotoxic doses, As significantly altered RAR-dependent gene transcription of a transfected RAR response element–luciferase construct and the native RA-inducible cytochrome P450 CYP26A gene in NT2 cells. Likewise, low-dose As significantly altered expression of a transfected TR response element–luciferase construct and the endogenous TR-regulated type I deiodinase (DIO1) gene in a similar manner in GH3 cells. An amphibian ex vivo tail metamorphosis assay was used to examine whether endocrine disruption by low-dose As could have specific pathophysiologic consequences, because tail metamorphosis is tightly controlled by TH through TR. TH-dependent tail shrinkage was inhibited in a dose-dependent manner by 0.1– 4.0 μM As. Conclusions: As had similar effects on RAR- and TR-mediated gene regulation as those previously observed for the steroid receptors, suggesting a common mechanism or action. Arsenic also profoundly affected a TR-dependent developmental process in a model animal system at very low concentrations. Because RAR and TH are critical for both normal human development and adult function and their dysregulation is associated with many disease processes, disruption of these hormone receptor–dependent processes by As is also potentially relevant to human developmental problems and disease risk

Self-complementary AAV Virus (scAAV) Safe and Long-term Gene Transfer in the Trabecular Meshwork of Living Rats and Monkeys

AAV vectors produce stable transgene expression and elicit low immune response in many tissues. AAVs have been the vectors of choice for gene therapy for the eye, in particular the retina. scAAVs are modified AAVs that bypass the required second-strand DNA synthesis to achieve transcription of the transgene. The goal was to investigate the ability of AAV vectors to induce long-term, safe delivery of transgenes to the trabecular meshwork of living animals

Comparison of inpatient vs. outpatient anterior cervical discectomy and fusion: a retrospective case series

<p>Abstract</p> <p>Background</p> <p>Spinal surgery is increasingly being done in the outpatient setting. We reviewed our experience with inpatient and outpatient single-level anterior cervical discectomy and fusion with plating (ACDF+P).</p> <p>Methods</p> <p>All patients undergoing single-level anterior cervical discectomy and fusion with plating between August 2005 and May 2007 by two surgeons (RPB or JAF) were retrospectively reviewed. All patients underwent anterior cervical microdiscectomy, arthrodesis using structural allograft, and titanium plating. A planned change from doing ACDF+P on an inpatient basis to doing ACDF+P on an outpatient basis was instituted at the midpoint of the study. There were no other changes in technique, patient selection, instrumentation, facility, or other factors. All procedures were done in full-service hospitals accommodating outpatient and inpatient care.</p> <p>Results</p> <p>64 patients underwent ACDF+P as inpatients, while 45 underwent ACDF+P as outpatients. When outpatient surgery was planned, 17 patients were treated as inpatients due to medical comorbidities (14), older age (1), and patient preference (2). At a mean follow-up of 62.4 days, 90 patients had an excellent outcome, 19 patients had a good outcome, and no patients had a fair or poor outcome. There was no significant difference in outcome between inpatients and outpatients. There were 4 complications, all occurring in inpatients: a hematoma one week post-operatively requiring drainage, a cerebrospinal fluid leak treated with lumbar drainage, syncope of unknown etiology, and moderate dysphagia.</p> <p>Conclusion</p> <p>In this series, outpatient ACDF+P was safe and was not associated with a significant difference in outcome compared with inpatient ACDF+P.</p