Sudden acquired retinal degeneration syndrome (SARDS) â a review and proposed strategies toward a better understanding of pathogenesis, early diagnosis, and therapy

Sudden acquired retinal degeneration syndrome (SARDS) is one of the leading causes of currently incurable canine vision loss diagnosed by veterinary ophthalmologists. The disease is characterized by acute onset of blindness due to loss of photoreceptor function, extinguished electroretinogram with an initially normal appearing ocular fundus, and mydriatic pupils which are slowly responsive to bright white light, unresponsive to red, but responsive to blue light stimulation. In addition to blindness, the majority of affected dogs also show systemic abnormalities suggestive of hyperadrenocorticism, such as polyphagia with resulting obesity, polyuria, polydipsia, and a subclinical hepatopathy. The pathogenesis of SARDS is unknown, but neuroendocrine and autoimmune mechanisms have been suggested. Therapies that target these disease pathways have been proposed to reverse or prevent further vision loss in SARDSâ affected dogs, but these treatments are controversial. In November 2014, the American College of Veterinary Ophthalmologists' Vision for Animals Foundation organized and funded a Think Tank to review the current knowledge and recently proposed ideas about disease mechanisms and treatment of SARDS. These panel discussions resulted in recommendations for future research strategies toward a better understanding of pathogenesis, early diagnosis, and potential therapy for this condition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122446/1/vop12291.pd

A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion

The mechanisms by which organisms adapt their growth according to the availability of oxygen are incompletely understood. Here the authors identify the D rosophila fat body as a tissue regulating growth in response to oxygen sensing via a mechanism involving Hph inhibition, HIF1-a activation and insulin secretion

Arginase impairs hypoxic pulmonary vasoconstriction in murine endotoxemia

Background: Hypoxic pulmonary vasoconstriction (HPV) optimizes the match between ventilation and perfusion in the lung by reducing blood flow to poorly ventilated regions. Sepsis and endotoxemia impair HPV. We previously showed that nitric oxide synthase 2 (NOS2) is required, but not sufficient, for the effect of endotoxin on HPV. The aim of the current study was to identify additional factors that might contribute to the impairment of HPV during endotoxemia. Methods: Gene expression profiling was determined using pulmonary tissues from NOS2-deficient (NOS2−/−) and wild-type mice subjected to endotoxin or saline challenge (control). HPV was accessed as the percentage increase in left pulmonary vascular resistance (LPVR) in response to left main bronchus occlusion (LMBO) in wild-type mice. Results: Among the 22,690 genes analyzed, endotoxin induced a greater than three-fold increase in 59 and 154 genes in the lungs of wild-type and NOS2−/− mice, respectively. Of all the genes induced by endotoxin in wild-type mice, arginase 1 (Arg1) showed the greatest increase (16.3-fold compared to saline treated wild-type mice). In contrast, endotoxin did not increase expression of Arg1 in NOS2−/− mice. There was no difference in the endotoxin-induced expression of Arg2 between wild-type and NOS2-deficient mice. We investigated the role of arginase in HPV by treating the mice with normal saline or the arginase inhibitor Nω-hydroxy-nor-L-arginine (norNOHA). In control mice (in the absence of endotoxin) treated with normal saline, HPV was intact as determined by profound LMBO-induced increase in LPVR (121 ± 22% from baseline). During endotoxemia and treatment with normal saline, HPV was impaired compared to normal saline treated control mice (33 ± 9% vs. 121 ± 22%, P < 0.05). HPV was restored in endotoxin-exposed mice after treatment with the arginase inhibitor norNOHA as shown by the comparison to endotoxemic mice treated with normal saline (113 ± 29% vs, 33 ± 9%, P < 0.05) and to control mice treated with normal saline (113 ± 29% vs, 121 ± 22%, P = 0.97). Conclusions: The results of this study suggest that endotoxemia induces Arg1 and that arginase contributes to the endotoxin-induced impairment of HPV in mice

Design, rationale, and baseline characteristics of a cluster randomized controlled trial of pay for performance for hypertension treatment: study protocol

<p>Abstract</p> <p>Background</p> <p>Despite compelling evidence of the benefits of treatment and well-accepted guidelines for treatment, hypertension is controlled in less than one-half of United States citizens.</p> <p>Methods/design</p> <p>This randomized controlled trial tests whether explicit financial incentives promote the translation of guideline-recommended care for hypertension into clinical practice and improve blood pressure (BP) control in the primary care setting. Using constrained randomization, we assigned 12 Veterans Affairs hospital outpatient clinics to four study arms: physician-level incentive; group-level incentive; combination of physician and group incentives; and no incentives (control). All participants at the hospital (cluster) were assigned to the same study arm. We enrolled 83 full-time primary care physicians and 42 non-physician personnel. The intervention consisted of an educational session about guideline-recommended care for hypertension, five audit and feedback reports, and five disbursements of incentive payments. Incentive payments rewarded participants for chart-documented use of guideline-recommended antihypertensive medications, BP control, and appropriate responses to uncontrolled BP during a prior four-month performance period over the 20-month intervention. To identify potential unintended consequences of the incentives, the study team interviewed study participants, as well as non-participant primary care personnel and leadership at study sites. Chart reviews included data collection on quality measures not related to hypertension. To evaluate the persistence of the effect of the incentives, the study design includes a washout period.</p> <p>Discussion</p> <p>We briefly describe the rationale for the interventions being studied, as well as the major design choices. Rigorous research designs such as the one described here are necessary to determine whether performance-based payment arrangements such as financial incentives result in meaningful quality improvements.</p> <p>Trial Registration</p> <p><url>http://www.clinicaltrials.gov</url><a href="http://www.clinicaltrials.gov/ct2/show/NCT00302718">NCT00302718</a></p

Evaluation of Long-Range Lightning Detection Networks Using TRMM/LIS Observations

Recent advances in long-range lightning detection technologies have improved our understanding of thunderstorm evolution in the data sparse oceanic regions. Although the expansion and improvement of long-range lightning datasets have increased their applicability, these applications (e.g., data assimilation, atmospheric chemistry, and aviation weather hazards) require knowledge of the network detection capabilities. Toward this end, the present study evaluates data from the World Wide Lightning Location Network (WWLLN) using observations from the Lightning Imaging Sensor (LIS) aboard the Tropical Rainfall Measurement Mission (TRMM) satellite. The study documents the WWLLN detection efficiency and location accuracy relative to LIS observations, describes the spatial variability in these performance metrics, and documents the characteristics of LIS flashes that are detected by WWLLN. Improved knowledge of the WWLLN detection capabilities will allow researchers, algorithm developers, and operational users to better prepare for the spatial and temporal coverage of the upcoming GOES-R Geostationary Lightning Mapper (GLM)

Persistence of Yersinia pestis in Soil Under Natural Conditions

As part of a fatal human plague case investigation, we showed that the plague bacterium, Yersinia pestis, can survive for at least 24 days in contaminated soil under natural conditions. These results have implications for defining plague foci, persistence, transmission, and bioremediation after a natural or intentional exposure to Y. pestis

Dynamic Career Models and Inequality Research: A Reexamination of the Sørensen Model

This article presents a reexamination of the Sørensen model. This model derives the pattern of individual careers from structural considerations. If longitudinal data on individual careers are available, Sørensen's model provides two methods to infer the underlying structural parameter. This structural parameter gives a useful measure for unequal career chances. An implementation of these methods, using firm data, shows, however, that they lead to contradictory conclusions; this is shown to be the result of some unrealistic assumptions Sørensen uses in his derivation. Some more realistic assumptions are suggested that produce reasonable results. Finally, it is shown that despite these modifications, the main conclusions of the Sørensen model are preserved. This seems to be promising for future work with this model

Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis

Background: Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute.Methods and Findings: In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting.Conclusions: These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite