Severity of Pain is not associated with Urgency of Diagnosis in ED Patients with Abdominal Pain

Background Abdominal Pain is the most common cause of visits to US Emergency Departments (EDs) and the causes range from urgent to non-urgent diagnoses. Distinguishing urgent versus non-urgent causes of abdominal pain is done through the use of clinical exam, lab studies and diagnostic imaging such as CT scans. There are no validated clinical decision rules to assist physicians in discriminating urgent from non-urgent causes of abdominal pain or which patient needs a CT scan. There is controversy regarding the use of CT scans for patients with abdominal pain due to the increased cost, radiation exposure and length of stay. Objective The objective of this study is to compare the demographics, pain score and CT utilization for patients with urgent versus non-urgent causes of abdominal pain. Methods At an academic ED, a convenience sample of patients with abdominal pain was prospectively enrolled by research assistants during the ED visit. Research assistants abstracted treatment information from the electronic medical record for the ED and hospitalization if applicable. Finally, enrollees were telephoned 2 weeks after the index ED visit to ascertain symptom resolution and treatment outcomes. Following establishment of final diagnosis, patients were classified as having an urgent or non-urgent diagnosis based upon published peer-reviewed criteria. Risk differences in pain severity, CT scan utilization and demographics were compared to urgency of diagnosis and a paired t-test was used to estimate differences in initial clinical characteristics. Results In a model of 725 patients, 144 had urgent diagnoses and 561 had non-urgent diagnoses. There was no distinction in insurance type, income level, mean age or pain score in the two groups. Ct scan utilization was higher in patients with urgent diagnoses (42.4% versus 16.4%.) Conclusion 20.4% of patients had an urgent diagnosis for the abdominal pain. There was no difference in the pain score for patients with urgent versus non-urgent diagnosis. While work-up bias is a potential limitation, CT scan utilization was higher in patients with an urgent diagnosis suggesting appropriate clinical judgement. Future studies will need to look at ways to target the testing to more high-risk patients who present with undifferentiated abdominal pain

Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains

AbstractWe previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al., Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions

Sloshing Gas in the Core of the Most Luminous Galaxy Cluster RXJ1347.5-1145

We present new constraints on the merger history of the most X-ray luminous cluster of galaxies, RXJ1347.5-1145, based its unique multiwavelength morphology. Our X-ray analysis confirms the core gas is undergoing "sloshing" resulting from a prior, large scale, gravitational perturbation. In combination with extensive multiwavelength observations, the sloshing gas points to the primary and secondary clusters having had at least two prior strong gravitational interactions. The evidence supports a model in which the secondary subcluster with mass M=4.8+/-2.4 x 10(exp 14) Stellar Mass has previously (> or approx.=0.6 Gyr ago) passed by the primary cluster, and has now returned for a subsequent crossing where the subcluster's gas has been completely stripped from its dark matter halo. RXJ1347 is a prime example of how core gas sloshing may be used to constrain the merger histories of galaxy clusters through multiwavelength analyses

Joint analysis of X-ray and Sunyaev Zel'dovich observations of galaxy clusters using an analytic model of the intra-cluster medium

We perform a joint analysis of X-ray and Sunyaev Zel'dovich (SZ) effect data using an analytic model that describes the gas properties of galaxy clusters. The joint analysis allows the measurement of the cluster gas mass fraction profile and Hubble constant independent of cosmological parameters. Weak cosmological priors are used to calculate the overdensity radius within which the gas mass fractions are reported. Such an analysis can provide direct constraints on the evolution of the cluster gas mass fraction with redshift. We validate the model and the joint analysis on high signal-to-noise data from the Chandra X-ray Observatory and the Sunyaev-Zel'dovich Array for two clusters, Abell 2631 and Abell 2204.Comment: ApJ in pres

A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference

BACKGROUND AND PURPOSE: Obesity and associated co‐morbidities, such as type 2 diabetes and non‐alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co‐morbidities. EXPERIMENTAL APPROACH: The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP‐089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight‐independent effects of KBP‐089 using a weight‐matched group. KEY RESULTS: Rats fed a high‐fat diet were treated, s.c., with KBP‐089 0.625, 1.25, 2.5 μg·kg(−1) or vehicle. KB‐089 induced in a dose‐dependent and sustained weight loss (~17% by 2.5 μg·kg(−1)). Moreover, KBP‐089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP‐089 improved glucose homeostasis through improved insulin action. To obtain a weight‐matched group, significantly less food was offered (9% less than in the KBP‐089 group). Weight matching led to improved glucose homeostasis by reducing plasma insulin; however, these effect were inferior compared to those of KBP‐089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP‐089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle. CONCLUSIONS AND IMPLICATIONS: The novel DACRA, KBP‐089, induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet‐induced weight loss

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Accumulation of Endogenous LITAF in Aggresomes

LITAF is a 161 amino acid cellular protein which includes a proline rich N-terminus and a conserved C-terminal domain known as the simple-like domain. Mutations in LITAF have been identified in Charcot-Marie tooth disease, a disease characterized by protein aggregates. Cells transfected with cellular LITAF reveal that LITAF is localized to late endosomes/lysosomes. Here we investigated the intracellular localization of endogenous LITAF. We demonstrated that endogenous LITAF accumulates at a discrete cytoplasmic site in BGMK cells that we identify as the aggresome. To determine the domain within LITAF that is responsible for the localization of LITAF to aggresomes, we created a construct that contained the C-terminal simple-like domain of LITAF and found that this construct also localizes to aggresomes. These data suggest the simple-like domain is responsible for targeting endogenous LITAF to the aggresome

Age- and season-dependent pattern of flavonol glycosides in Cabernet Sauvignon grapevine leaves

Flavonols play key roles in many plant defense mechanisms, consequently they are frequently investigated as stress sensitive factors in relation to several oxidative processes. It is well known that grapevine (Vitis vinifera L.) can synthesize various flavonol glycosides in the leaves, however, very little information is available regarding their distribution along the cane at different leaf levels. In this work, taking into consideration of leaf position, the main flavonol glycosides of a red grapevine cultivar (Cabernet Sauvignon) were profiled and quantified by HPLC–DAD analysis. It was found that amount of four flavonol glycosides, namely, quercetin-3-O-galactoside, quercetin-3-O-glucoside, kaempferol-3-O-glucoside and kaempferol-3-O-glucuronide decreased towards the shoot tip. Since leaf age also decreases towards the shoot tip, the obtained results suggest that these compounds continuously formed by leaf aging, resulting in their accumulation in the older leaves. In contrast, quercetin-3-O-glucuronide (predominant form) and quercetin-3-O-rutinoside were not accumulated significantly by aging. We also pointed out that grapevine boosted the flavonol biosynthesis in September, and flavonol profile differed significantly in the two seasons. Our results contribute to the better understanding of the role of flavonols in the antioxidant defense system of grapevine

BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1

<p>Abstract</p> <p>Background</p> <p>Microdeletion of the chromosome 22q11.2 region is the most common genetic aberration among patients with velocardiofacial syndrome (VCFS) but a subset of subjects do not show alterations of this chromosome region.</p> <p>Methods</p> <p>We analyzed 18 patients with VCFS-like features by comparative genomic hybridisation (aCGH) array and performed a face-to-face slide hybridization with two different arrays: a whole genome and a chromosome 22-specific BAC array. Putative rearrangements were confirmed by FISH and MLPA assays.</p> <p>Results</p> <p>One patient carried a combination of rearrangements on 1q21.1, consisting in a microduplication of 212 kb and a close microdeletion of 1.15 Mb, previously reported in patients with variable phenotypes, including mental retardation, congenital heart defects (CHD) and schizophrenia. While 326 control samples were negative for both 1q21.1 rearrangements, one of 73 patients carried the same 212-kb microduplication, reciprocal to TAR microdeletion syndrome. Also, we detected four copy number variants (CNVs) inherited from one parent (a 744-kb duplication on 10q11.22; a 160 kb duplication and deletion on 22q11.21 in two cases; and a gain of 140 kb on 22q13.2), not present in control subjects, raising the potential role of these CNVs in the VCFS-like phenotype.</p> <p>Conclusions</p> <p>Our results confirmed aCGH as a successful strategy in order to characterize additional submicroscopic aberrations in patients with VCF-like features that fail to show alterations in 22q11.2 region. We report a 212-kb microduplication on 1q21.1, detected in two patients, which may contribute to CHD.</p