Quantitative sensory testing in children with sickle cell disease: additional insights and future possibilities.

Quantitative sensory testing (QST) is used in a variety of pain disorders to characterize pain and predict prognosis and response to specific therapies. In this study, we aimed to confirm results in the literature documenting altered QST thresholds in sickle cell disease (SCD) and assess the test-retest reliability of results over time. Fifty-seven SCD and 60 control subjects aged 8-20 years underwent heat and cold detection and pain threshold testing using a Medoc TSAII. Participants were tested at baseline and 3 months; SCD subjects were additionally tested at 6 months. An important facet of our study was the development and use of a novel QST modelling approach, allowing us to model all data together across modalities. We have not demonstrated significant differences in thermal thresholds between subjects with SCD and controls. Thermal thresholds were consistent over a 3- to 6-month period. Subjects on whom hydroxycarbamide (HC) was initiated shortly before or after baseline testing (new HC users) exhibited progressive decreases in thermal sensitivity from baseline to 6 months, suggesting that thermal testing may be sensitive to effective therapy to prevent vasoocclusive pain. These findings inform the use of QST as an endpoint in the evaluation of preventative pain therapies

Comparison of human uterine cervical electrical impedance measurements derived using two tetrapolar probes of different sizes

BACKGROUND We sought to compare uterine cervical electrical impedance spectroscopy measurements employing two probes of different sizes, and to employ a finite element model to predict and compare the fraction of electrical current derived from subepithelial stromal tissue. METHODS Cervical impedance was measured in 12 subjects during early pregnancy using 2 different sizes of the probes on each subject. RESULTS Mean cervical resistivity was significantly higher (5.4 vs. 2.8 Ωm; p < 0.001) with the smaller probe in the frequency rage of 4–819 kHz. There was no difference in the short-term intra-observer variability between the two probes. The cervical impedance measurements derived in vivo followed the pattern predicted by the finite element model. CONCLUSION Inter-electrode distance on the probes for measuring cervical impedance influences the tissue resistivity values obtained. Determining the appropriate probe size is necessary when conducting clinical studies of resistivity of the cervix and other human tissues

Predictors of drinking and functional outcomes for men and women following inpatient alcohol treatment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106952/1/ajad12098.pd

The Ursinus Weekly, November 16, 1906

Football • Personals • Society notes • Meeting of the Directors of Ursinus College • Alumni notes • School of Theology • Ursinus Union • Literary Supplement: The garden of the Lord; Wanted: An instructor; Socialism; Our poet traveler; The little red school house on the hill; Just a modest Irish maid • Exchangeshttps://digitalcommons.ursinus.edu/weekly/2921/thumbnail.jp

Rigorous Computational and Experimental Investigations on MDM2/MDMX-Targeted Linear and Macrocyclic Peptides

There is interest in peptide drug design, especially for targeting intracellular protein–protein interactions. Therefore, the experimental validation of a computational platform for enabling peptide drug design is of interest. Here, we describe our peptide drug design platform (CMDInventus) and demonstrate its use in modeling and predicting the structural and binding aspects of diverse peptides that interact with oncology targets MDM2/MDMX in comparison to both retrospective (pre-prediction) and prospective (post-prediction) data. In the retrospective study, CMDInventus modules (CMDpeptide, CMDboltzmann, CMDescore and CMDyscore) were used to accurately reproduce structural and binding data across multiple MDM2/MDMX data sets. In the prospective study, CMDescore, CMDyscore and CMDboltzmann were used to accurately predict binding affinities for an Ala-scan of the stapled α-helical peptide ATSP-7041. Remarkably, CMDboltzmann was used to accurately predict the results of a novel D-amino acid scan of ATSP-7041. Our investigations rigorously validate CMDInventus and support its utility for enabling peptide drug design

The Palomar Transient Factory Orion Project: Eclipsing Binaries and Young Stellar Objects

The Palomar Transient Factory (PTF) Orion project is an experiment within the broader PTF survey, a systematic automated exploration of the sky for optical transients. Taking advantage of the wide field of view available using the PTF camera at the Palomar 48" telescope, 40 nights were dedicated in December 2009-January 2010 to perform continuous high-cadence differential photometry on a single field containing the young (7-10Myr) 25 Ori association. The primary motivation for the project is to search for planets around young stars in this region. The unique data set also provides for much ancillary science. In this first paper we describe the survey and data reduction pipeline, and present initial results from an inspection of the most clearly varying stars relating to two of the ancillary science objectives: detection of eclipsing binaries and young stellar objects. We find 82 new eclipsing binary systems, 9 of which we are candidate 25 Ori- or Orion OB1a-association members. Of these, 2 are potential young W UMa type systems. We report on the possible low-mass (M-dwarf primary) eclipsing systems in the sample, which include 6 of the candidate young systems. 45 of the binary systems are close (mainly contact) systems; one shows an orbital period among the shortest known for W UMa binaries, at 0.2156509 \pm 0.0000071d, with flat-bottomed primary eclipses, and a derived distance consistent with membership in the general Orion association. One of the candidate young systems presents an unusual light curve, perhaps representing a semi-detached binary system with an inflated low-mass primary or a star with a warped disk, and may represent an additional young Orion member. Finally, we identify 14 probable new classical T-Tauri stars in our data, along with one previously known (CVSO 35) and one previously reported as a candidate weak-line T-Tauri star (SDSS J052700.12+010136.8).Comment: 66 pages, 27 figures, accepted to Astronomical Journal. Minor typographical corrections and update to author affiliation

The PTF Orion Project: a Possible Planet Transiting a T-Tauri Star

We report observations of a possible young transiting planet orbiting a previously known weak-lined T-Tauri star in the 7-10 Myr old Orion-OB1a/25-Ori region. The candidate was found as part of the Palomar Transient Factory (PTF) Orion project. It has a photometric transit period of 0.448413 +- 0.000040 days, and appears in both 2009 and 2010 PTF data. Follow-up low-precision radial velocity (RV) observations and adaptive optics imaging suggest that the star is not an eclipsing binary, and that it is unlikely that a background source is blended with the target and mimicking the observed transit. RV observations with the Hobby-Eberly and Keck telescopes yield an RV that has the same period as the photometric event, but is offset in phase from the transit center by approximately -0.22 periods. The amplitude (half range) of the RV variations is 2.4 km/s and is comparable with the expected RV amplitude that stellar spots could induce. The RV curve is likely dominated by stellar spot modulation and provides an upper limit to the projected companion mass of M_p sin i_orb < 4.8 +- 1.2 M_Jup; when combined with the orbital inclination, i orb, of the candidate planet from modeling of the transit light curve, we find an upper limit on the mass of the planetary candidate of M_p < 5.5 +- 1.4 M_Jup. This limit implies that the planet is orbiting close to, if not inside, its Roche limiting orbital radius, so that it may be undergoing active mass loss and evaporation.Comment: Corrected typos, minor clarifications; minor updates/corrections to affiliations and bibliography. 35 pages, 10 figures, 3 tables. Accepted to Ap

Primary care incidence and treatment of four neuropathic pain conditions: A descriptive study, 2002–2005

<p>Abstract</p> <p>Background</p> <p>Between 1992 and 2001 the UK general practice incidence of post-herpetic neuralgia and trigeminal neuralgia declined, whilst the incidence of painful diabetic neuropathy increased. The most common first line treatments were compound analgesics. As therapeutic options have subsequently changed, this study presents updated data on incidence and prescribing patterns in neuropathic pain.</p> <p>Methods</p> <p>A descriptive analysis of the epidemiology and prescription treatment at diagnosis of incident post-herpetic neuralgia (n = 1,923); trigeminal neuralgia (1,862); phantom limb pain (57) and painful diabetic neuropathy (1,444) using computerised UK general practice records (THIN): May 2002 to July 2005.</p> <p>Results</p> <p>Primary care incidences per 100,000 person years observation of 28 (95% confidence interval (CI) 27–30) for post-herpetic neuralgia, 27 (95%CI 26–29) for trigeminal neuralgia, 0.8 (95%CI 0.6–1.1) for phantom limb pain and 21 (95%CI 20–22) for painful diabetic neuropathy are reported. The most common initial treatments were tricyclic antidepressants (post-herpetic neuralgia) or antiepileptics (trigeminal neuralgia and painful diabetic neuropathy) and opioid analgesics (phantom limb pain). The mean number of changes before a stable drug regimen was 1.2 to 1.5 for trigeminal neuralgia, painful diabetic neuropathy and post-herpetic neuralgia, and 2.4 for phantom limb pain.</p> <p>Conclusion</p> <p>The incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant. Despite more frequent use of antidepressants and antiepileptics for first line treatment, as opposed to conventional non-opioid analgesics, changes to therapy are common before a stable regimen is reached.</p

Genome-scale resources for Thermoanaerobacterium saccharolyticum

Background Thermoanaerobacterium saccharolyticum is a hemicellulose-degrading thermophilic anaerobe that was previously engineered to produce ethanol at high yield. A major project was undertaken to develop this organism into an industrial biocatalyst, but the lack of genome information and resources were recognized early on as a key limitation. Results Here we present a set of genome-scale resources to enable the systems level investigation and development of this potentially important industrial organism. Resources include a complete genome sequence for strain JW/SL-YS485, a genome-scale reconstruction of metabolism, tiled microarray data showing transcription units, mRNA expression data from 71 different growth conditions or timepoints and GC/MS-based metabolite analysis data from 42 different conditions or timepoints. Growth conditions include hemicellulose hydrolysate, the inhibitors HMF, furfural, diamide, and ethanol, as well as high levels of cellulose, xylose, cellobiose or maltodextrin. The genome consists of a 2.7 Mbp chromosome and a 110 Kbp megaplasmid. An active prophage was also detected, and the expression levels of CRISPR genes were observed to increase in association with those of the phage. Hemicellulose hydrolysate elicited a response of carbohydrate transport and catabolism genes, as well as poorly characterized genes suggesting a redox challenge. In some conditions, a time series of combined transcription and metabolite measurements were made to allow careful study of microbial physiology under process conditions. As a demonstration of the potential utility of the metabolic reconstruction, the OptKnock algorithm was used to predict a set of gene knockouts that maximize growth-coupled ethanol production. The predictions validated intuitive strain designs and matched previous experimental results. Conclusion These data will be a useful asset for efforts to develop T. saccharolyticum for efficient industrial production of biofuels. The resources presented herein may also be useful on a comparative basis for development of other lignocellulose degrading microbes, such as Clostridium thermocellum. Electronic supplementary material The online version of this article (doi:10.1186/s12918-015-0159-x) contains supplementary material, which is available to authorized users