Normative and critical criteria for iliotibial band and iliopsoas muscle flexibility

Context: The Ober and Thomas tests are subjective and involve a "negative" or "positive" assessment, making them difficult to apply within the paradigm of evidence-based medicine. No authors have combined the subjective clinical assessment with an objective measurement for these special tests. Objective: To compare the subjective assessment of iliotibial band and iliopsoas flexibility with the objective measurement of a digital inclinometer, to establish normative values, and to provide an evidence-based critical criterion for determining tissue tightness. Design: Cross-sectional study. Setting: Clinical research laboratory. Patients or Other Participants: Three hundred recreational athletes (125 men, 175 women; 250 in injured group, 50 in control group). Main Outcome Measure(s): Iliotibial band and iliopsoas muscle flexibility were determined subjectively using the modified Ober and Thomas tests, respectively. Using a digital inclinometer, we objectively measured limb position. lnterrater reliability for the subjective assessment was compared between 2 clinicians for a random sample of 100 injured participants, who were classified subjectively as either negative or positive for iliotibial band and iliopsoas tightness. Percentage of agreement indicated interrater reliability for the subjective assessment. Results: For iliotibial band flexibility, the average inclinometer angle was -24.59 degrees +/- 7.27 degrees. A total of 432 limbs were subjectively assessed as negative (-27.13 degrees +/- 5.53 degrees) and 168 as positive (-16.29 degrees +/- 6.87 degrees). For iliopsoas flexibility, the average inclinometer angle was -10.60 degrees +/- 9.61 degrees. A total of 392 limbs were subjectively assessed as negative (-15.51 degrees +/- 5.82 degrees) and 208 as positive (0.34 degrees +/- 7.00 degrees). The critical criteria for iliotibial band and iliopsoas flexibility were determined to be -23.16 degrees and -9.69 degrees, respectively. Between-clinicians agreement was very good, ranging from 95.0% to 97.6% for the Thomas and Ober tests, respectively. Conclusions: Subjective assessments and instrumented measurements were combined to establish normative values and critical criterions for tissue flexibility for the modified Ober and Thomas tests

Reflective Dialogue across Differences in Libraries

Chapter from "Libraries Promoting Reflective Dialogue in a Time of Political Polarization," edited by Andrea Baer, Ellysa Cahoy, and Bob Schroeder

Human olfactory mesenchymal stromal cell transplantation ameliorates experimental autoimmune encephalomyelitis revealing an inhibitory role for IL16 on myelination

One of the therapeutic approaches for the treatment of the autoimmune demyelinating disease, multiple sclerosis (MS) is bone marrow mesenchymal stromal cell (hBM-MSCs) transplantation. However, given their capacity to enhance myelination in vitro, we hypothesised that human olfactory mucosa-derived MSCs (hOM-MSCs) may possess additional properties suitable for CNS repair. Herein, we have examined the efficacy of hOM-MSCs versus hBM-MSCs using the experimental autoimmune encephalomyelitis (EAE) model. Both MSC types ameliorated disease, if delivered during the initial onset of symptomatic disease. Yet, only hOM-MSCs improved disease outcome if administered during established disease when animals had severe neurological deficits. Histological analysis of spinal cord lesions revealed hOM-MSC transplantation reduced blood–brain barrier disruption and inflammatory cell recruitment and enhanced axonal survival. At early time points post-hOM-MSC treatment, animals had reduced levels of circulating IL-16, which was reflected in both the ability of immune cells to secrete IL-16 and the level of IL-16 in spinal cord inflammatory lesions. Further in vitro investigation revealed an inhibitory role for IL-16 on oligodendrocyte differentiation and myelination. Moreover, the availability of bioactive IL-16 after demyelination was reduced in the presence of hOM-MSCs. Combined, our data suggests that human hOM-MSCs may have therapeutic benefit in the treatment of MS via an IL-16-mediated pathway, especially if administered during active demyelination and inflammation

Identification of A Novel Class of Benzofuran Oxoacetic Acid-Derived Ligands that Selectively Activate Cellular EPAC1

Cyclic AMP promotes EPAC1 and EPAC2 activation through direct binding to a specific cyclic nucleotide-binding domain (CNBD) within each protein, leading to activation of Rap GTPases, which control multiple cell responses, including cell proliferation, adhesion, morphology, exocytosis, and gene expression. As a result, it has become apparent that directed activation of EPAC1 and EPAC2 with synthetic agonists may also be useful for the future treatment of diabetes and cardiovascular diseases. To identify new EPAC agonists we have developed a fluorescent-based, ultra-high-throughput screening (uHTS) assay that measures the displacement of binding of the fluorescent cAMP analogue, 8-NBD-cAMP to the EPAC1 CNBD. Triage of the output of an approximately 350,000 compound screens using this assay identified a benzofuran oxaloacetic acid EPAC1 binder (SY000) that displayed moderate potency using orthogonal assays (competition binding and microscale thermophoresis). We next generated a limited library of 91 analogues of SY000 and identified SY009, with modifications to the benzofuran ring associated with a 10-fold increase in potency towards EPAC1 over SY000 in binding assays. In vitro EPAC1 activity assays confirmed the agonist potential of these molecules in comparison with the known EPAC1 non-cyclic nucleotide (NCN) partial agonist, I942. Rap1 GTPase activation assays further demonstrated that SY009 selectively activates EPAC1 over EPAC2 in cells. SY009 therefore represents a novel class of NCN EPAC1 activators that selectively activate EPAC1 in cellulae

The worldwide marine radiocarbon reservoir effect: definitions, mechanisms, and prospects

When a carbon reservoir has a lower radiocarbon content than the atmosphere, this is referred to as a reservoir effect. This is expressed as an offset between the radiocarbon ages of samples from the two reservoirs at a single point in time. The marine reservoir effect (MRE) has been a major concern in the radiocarbon community, as it introduces an additional source of error that is often difficult to accurately quantify. For this reason, researchers are often reluctant to date marine material where they have another option. The influence of this phenomenon makes the study of the MRE important for a broad range of applications. The advent of Accelerator Mass Spectrometry (AMS) has reduced sample size requirements and increased measurement precision, in turn increasing the number of studies seeking to measure marine samples. These studies rely on overcoming the influence of the MRE on marine radiocarbon dates through the worldwide quantification of the local parameter ΔR, that is, the local variation from the global average MRE. Furthermore, the strong dependence on ocean dynamics makes the MRE a useful indicator for changes in oceanic circulation, carbon exchange between reservoirs, and the fate of atmospheric CO2, all of which impact Earth's climate. This article explores data from the Marine Reservoir Database and reviews the place of natural radiocarbon in oceanic records, focusing on key questions (e.g., changes in ocean dynamics) that have been answered by MRE studies and on their application to different subjects

Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors

Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-beta-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential beta-lactamase stable beta-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.Peer reviewe

Reading and Ownership

First paragraph: ‘It is as easy to make sweeping statements about reading tastes as to indict a nation, and as pointless.’ This jocular remark by a librarian made in the Times in 1952 sums up the dangers and difficulties of writing the history of reading. As a field of study in the humanities it is still in its infancy and encompasses a range of different methodologies and theoretical approaches. Historians of reading are not solely interested in what people read, but also turn their attention to the why, where and how of the reading experience. Reading can be solitary, silent, secret, surreptitious; it can be oral, educative, enforced, or assertive of a collective identity. For what purposes are individuals reading? How do they actually use books and other textual material? What are the physical environments and spaces of reading? What social, educational, technological, commercial, legal, or ideological contexts underpin reading practices? Finding answers to these questions is compounded by the difficulty of locating and interpreting evidence. As Mary Hammond points out, ‘most reading acts in history remain unrecorded, unmarked or forgotten’. Available sources are wide but inchoate: diaries, letters and autobiographies; personal and oral testimonies; marginalia; and records of societies and reading groups all lend themselves more to the case-study approach than the historical survey. Statistics offer analysable data but have the effect of producing identikits rather than actual human beings. The twenty-first century affords further possibilities, and challenges, with its traces of digital reader activity, but the map is ever-changing

Schoolbooks and textbook publishing.

In this chapter the author looks at the history of schoolbooks and textbook publishing. The nineteenth century saw a rise in the school book market in Britain due to the rise of formal schooling and public examinations. Although the 1870 Education and 1872 (Scotland) Education Acts made elementary education compulsory for childern between 5-13 years old, it was not until the end of the First World War that some sort form of secondary education became compulsory for all children