Differential Expression of Novel Adiponectin Receptor-1 Transcripts in Skeletal Muscle of Subjects With Normal Glucose Tolerance and Type 2 Diabetes

OBJECTIVE—Adiponectin receptor-1 (AdipoR1) expression in skeletal muscle has been suggested to play an important role in insulin resistance and diabetes. We aimed at evaluating the presence of novel AdiopR1 splice variants in human muscle and their regulation under physiological and pathophysiological states. RESEARCH DESIGN AND METHODS—AdipoR1 59UTR mRNA transcripts, predicted from bioinformatics data, were eval-uated in fetal and adult human tissues. Expression and function of the identified transcripts were assessed in cultured human skeletal muscle cells and in muscle biopsies obtained from indi-viduals with normal glucose tolerance (NGT) and type 2 diabetes (n = 49). RESULTS—Screening of potential AdipoR1 59UTR splice variants revealed a novel highly abundant muscle transcript (R1T3) in ad-dition to the previously described transcript (R1T1). Unlike R1T1

Cutaneous neurofibromas Current clinical and pathologic issues

ObjectiveTo present the current terminology and natural history of neurofibromatosis 1 (NF1) cutaneous neurofibromas (cNF).MethodsNF1 experts from various research and clinical backgrounds reviewed the terms currently in use for cNF as well as the clinical, histologic, and radiographic features of these tumors using published and unpublished data.ResultsNeurofibromas develop within nerves, soft tissue, and skin. The primary distinction between cNF and other neurofibromas is that cNF are limited to the skin whereas other neurofibromas may involve the skin, but are not limited to the skin. There are important cellular, molecular, histologic, and clinical features of cNF. Each of these factors is discussed in consideration of a clinicopathologic framework for cNF.ConclusionThe development of effective therapies for cNF requires formulation of diagnostic criteria that encompass the clinical and histologic features of these tumors. However, there are several areas of overlap between cNF and other neurofibromas that make distinctions between cutaneous and other neurofibromas more difficult, requiring careful deliberation with input across the multiple disciplines that encounter these tumors and ultimately, prospective validation. The ultimate goal of this work is to facilitate accurate diagnosis and meaningful therapeutics for cNF

Anti-Neuroinflammatory effects of the extract of Achillea fragrantissima

<p>Abstract</p> <p>Background</p> <p>The neuroinflammatory process plays a central role in the initiation and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, and involves the activation of brain microglial cells. During the neuroinflammatory process, microglial cells release proinflammatory mediators such as cytokines, matrix metalloproteinases (MMP), Reactive oxygen species (ROS) and nitric oxide (NO). In the present study, extracts from 66 different desert plants were tested for their effect on lipopolysaccharide (LPS) - induced production of NO by primary microglial cells. The extract of <it>Achillea fragrantissima </it>(<it>Af</it>)<it/>, which is a desert plant that has been used for many years in traditional medicine for the treatment of various diseases, was the most efficient extract, and was further studied for additional anti-neuroinflammatory effects in these cells.</p> <p>Methods</p> <p>In the present study, the ethanolic extract prepared from <it>Af </it>was tested for its anti-inflammatory effects on lipopolysaccharide (LPS)-activated primary cultures of brain microglial cells. The levels of the proinflammatory cytokines interleukin1β (IL-1β) and tumor necrosis factor-α (TNFα) secreted by the cells were determined by reverse transcriptase-PCR and Enzyme-linked immunosorbent assay (ELISA), respectively. NO levels secreted by the activate cells were measured using Griess reagent, ROS levels were measured by 2'7'-dichlorofluorescein diacetate (DCF-DA), MMP-9 activity was measured using gel zymography, and the protein levels of the proinflammatory enzymes cyclooxygenase-2 (COX-2) and induced nitric oxide synthase (iNOS) were measured by Western blot analysis. Cell viability was assessed using Lactate dehydrogenase (LDH) activity in the media conditioned by the cells or by the crystal violet cell staining.</p> <p>Results</p> <p>We have found that out of the 66 desert plants tested, the extract of <it>Af </it>was the most efficient extract and inhibited ~70% of the NO produced by the LPS-activated microglial cells, without affecting cell viability. In addition, this extract inhibited the LPS - elicited expression of the proinflammatory mediators IL-1β, TNFα, MMP-9, COX-2 and iNOS in these cells.</p> <p>Conclusions</p> <p>Thus, phytochemicals present in the <it>Af </it>extract could be beneficial in preventing/treating neurodegenerative diseases in which neuroinflammation is part of the pathophysiology.</p

Contract’s Meaning and the Histories of Classical Contract Law

This paper argues that histories of nineteenth-century contract have been implicated in the creation of a questionable historical artifact: the story of a single meaning of contract at the decisive era for modern contract law’s development, a story intimately tied with atomistic individualism.The paper traces how the consensus has been built and kept beyond debate despite significant controversies engaging rival historical schools of nineteenth-century contract law. It does so by critically synthesizing multiple accounts of contract law, produced from the nineteenth century to our own days. It opens, however, with a brief literary excursion in order to show that there is good reason to view the consensus as unwarranted. An individualist but relational version of contract was dominant in Victorian literary realism, one of the central cultural sites of the “Age of Contract”, problematizing the story of a single meaning of contract.The consensus created by contract histories bears implications for present thought as it negotiates visions of contract, and as it explores law’s constitutive effects on social consciousness. This paper lays the consensus open so that we can let go of it.Cet article soutient que l’histoire des contrats du XIXe siècle fut impliquée dans la création d’un artefact historique discutable : le développement d’une seule et unique interprétation du contrat à une époque décisive pour le développement du droit contractuel moderne, un développement intimement liée à l’individualisme atomistique.Cet article retrace la façon dont ce consensus se développa à l’écart de réels débats, en dépit d’importantes controverses opposant plusieurs écoles de pensée historiques du droit contractuel du XIXe siècle. Pour ce faire, l’article résume de manière critique plusieurs exemples du droit des contrats du XIXe siècle à nos jours. L’article débute avec une brève excursion littéraire afin de démontrer qu’il existe de bonnes raisons de douter que le consensus soit justifié. Une version individualiste mais relationnelle du contrat était dominante dans le réalisme littéraire de l’époque victorienne, l’un des principaux sites culturels de l’« Ère du contrat », rendant problématique la théorie d’une unique signification du contrat.Le consensus créé par l’histoire des contrats influence la pensée actuelle puisqu’il concerne l’interprétation des contrats et explore les effets constitutifs du droit sur la conscience sociale. Cet article met à nu le consensus afin qu’il puisse être reconsidéré

The Realism of the Balance Sheet: Value Assessments Between the Debtors Act and The Picture of Dorian Gray

This essay examines English parliamentary debates about consumers’ financial means in the context of the 1869 Debtors Act, which oversaw working-class imprisonment for debt. Debates reveal a shift in the financial epistemology favored by participants, from a view of means based on what I term social credit, to a view of means based on a balance-sheet paradigm. The rise and naturalization of the balance-sheet paradigm was both interrogated and challenged by one of the era’s most controversial texts, Oscar Wilde’s The Picture of Dorian Gray. I rely on the novel to examine the deep implications of the shift for the history of consumption, and to recall the drama it involved

Arts and the Aesthetic in Legal History

This special issue of Critical Analysis of Law brings together a rich array of articles at the intersections of arts and legal history. In this introduction we reflect on some of the benefits and implications of this interdisciplinary juncture, which contemporary legal historians have been slow to engage. We highlight the significance of engaging with the arts for theoretical conundrums central to legal history: art as source, the philosophy of time, methodological scripts, and the relation of the descriptive to the normative. The arts, we argue, prove vital in tackling and breaching the limits of imagination imposed by our time and place—disciplinary place included

Burnout among family medicine residents: a cross-sectional nationwide study

Abstract Background In addition to pressures typical of other medical professions, family physicians face additional challenges such as building long-term relationships with patients, dealing with patients' social problems, and working at a high level of uncertainty. We aimed to assess the rate of burnout and factors associated with it among family medicine residents throughout Israel. Methods A cross sectional study based on a self-administered questionnaire. Results Ninety family medicine residents throughout Israel completed the questionnaire. The rate of clinically significant burnout, assessed by the composite Shirom-Melamed Burnout Questionnaire score, was 14.4%. In univariate analyses several personal and professional characteristics, as well as all tested psychological characteristics, showed significant associations with burnout. However, in the multivariable logistic regression only psychological work-related characteristics (work engagement, psychological flexibility (reverse scoring), and perceived work-related stress) were significantly associated with burnout at OR (95% CI) = 0.23 (0.06–0.60), 1.31 (1.10–1.71), and 1.16 (1.05–3.749), respectively. Conclusion The integration of burnout prevention programs into academic courses during residency could explain the relatively low prevalence of burnout among family medicine residents in this study. Given the strong association of burnout with psychological characteristics, further investment in burnout prevention through targeted structured courses for residents should be encouraged

Malignant Transformation of Neurofibromas in Neurofibromatosis 1 Is Associated with CDKN2A/p16 Inactivation

Patients with neurofibromatosis 1 (NF1) are predisposed to develop multiple neurofibromas (NFs) and are at risk for transformation of NFs to malignant peripheral nerve sheath tumors (MPNSTs). Little is known, however, about the biological events involved in the malignant transformation of NFs. We examined the CDKN2A/p16 gene and p16 protein in NFs and MPNSTs from patients with NF1. On immunohistochemical analysis, all NFs expressed p16 protein. The MPNSTs, however, were essentially immunonegative for p16, with striking transitions in cases that contained both benign and malignant elements. None of the benign tumors had CDKN2A/p16 deletions, whereas three of six MPNSTs appeared to have homozygous CDKN2A/p16 deletions. Methylation analysis and mutation analysis of CDKN2A/p16 in MPNSTs did not reveal any abnormalities. These results show that malignant transformation of NF is associated with loss of p16 expression, which is often secondary to homozygous deletion of the CDKN2A/p16 gene. The findings suggest that CDKN2A/p16 inactivation occurs during the malignant transformation of NFs in NF1 patients and raises the possibility that p16 immunohistochemistry may provide ancillary information in the distinction of NF from MPNST