The new issue is now available.JAPAN TAPPI JOURNAL

Vol.69 No.12

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Rosai–Dorfman Disease Harboring an Activating KRAS K117N Missense Mutation

Abstract

Rosai–Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare histiocytic proliferation that is generally considered to be reactive with a benign clinical course. The etiology of RDD is very poorly understood. Recent studies have shown frequent BRAF, NRAS, KRAS, and PIK3CA activating mutations in several histiocytic neoplasms highlighting the emerging importance of the RAF/MEK/ERK pathway in the pathogenesis of these diseases. Here we report a case of Rosai–Dorfman disease involving the submandibular salivary gland with a KRAS K117N missense mutation discovered by next-generation sequencing. These results suggest that at least a subset of RDD cases may be clonal processes. Further mutational studies on this rare histiocytic disease should be undertaken to better characterize its pathogenesis as well as open up potential avenues for therapy.

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Ivory Harvesting Pressure on the Genome of the African Elephant: A Phenotypic Shift to Tusklessness

Abstract

The unique chequered pattern of elephant ivory has made it a desired commodity for the production of various works of art. The demand however outstrips the supply and with soaring prices, illegal tusk harvesting is thriving on the African continent. Formal restrictions placed on trade in elephant products have been ineffective in reversing the rapid decline in elephant numbers. We are presently facing the reality of extinction of free roaming elephant on the African continent. This paper describes the histogenesis of the chequered pattern, the genomic impact of ivory harvesting on the phenotype of breeding herds, and the contribution of science to tracing the origin of illegal ivory.

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The impact of gestational weight gain in different trimesters of pregnancy on glucose challenge test and gestational diabetes

Purpose

Assessing the effects of excessive weight gain before pregnancy, in the first and second trimesters and in the month preceding glucose challenge test (GCT) on GCT results and gestational diabetes mellitus (GDM).

Study design

This prospective cohort study evaluated 1279 pregnant women who were referred for their first prenatal visit in 2012–2015. Mother’s body mass index (BMI) was recorded before pregnancy, during the first visit and every 4 weeks until 28 gestational weeks. All mothers underwent GCT at 28 weeks and when 1 h glucose ≥140 mg/dL (≥7.8 mmol/L), they were referred for a 100 g fasting glucose 3 h glucose tolerance test.

Results

Obesity and being overweight prior to pregnancy were associated with 2.8-fold and 1.5-fold higher rates of developing GDM (p<0.001, p=0.04) and 1.9-fold and 1.8-fold higher rates of having false-positive GCT results (p<0.001). First-trimester excessive weight gain was significantly associated with false-positive GCT in women who were lean, overweight and obese before pregnancy (all p<0.001). When these women kept gaining excessive weight during the subsequent period the risk of developing GDM was significantly increased regardless of their pre-pregnancy BMI (p=0.03). When these women adhered to the recommended weight gain during the subsequent period, the risk of developing GDM was not increased, however the risk of having false-positive GCT remained high (p<0.001).

Conclusions

Elevated pre-pregnancy BMI independently increases the risk of GDM and false-positive GCT. First trimester weight gain is the most important predictor of GCT and GDM regardless of pre-pregnancy BMI. The weight gain during the subsequent period affects the risk of developing GDM only in women with excessive first-trimester weight gain.

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Simulation-based training: the missing link to lastingly improved patient safety and health?

Introduction

Patient harm resulting from medical care is common, with 25.1 harms per 100 hospital admissions and 10.9% of harms being life threatening and causing or contributing to a patient’s death.1 One study found at least 210 000 deaths of hospitalised patients to be associated with preventable harm per year.2 Factors contributing most frequently to patient safety incidents are active failures including cognitive and technical errors as well as deviations from policies, individual factors (eg, inexperience and stress), communication, equipment and supplies, and management of staff and staffing levels.3

As factors contributing to safety incidents are manifold, a multitude of strategies—involving the continuum from individuals to healthcare systems—has to be considered when aiming at improving the quality of healthcare and patient safety. A strategy certainly at the forefront of this process is active improvement of quality and effectiveness in medical education and training.4

Medical education…

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Immunotherapy Continues to Advance in Head and Neck Cancer

Source: http://www.onclive.com Author: Megan Garlapow, PhD Concomitant administration of motolimod with cetuximab (Erbitux) increases the innate and adaptive immune response in the blood and the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC), overcoming negative prognostic biomarkers of cetuximab therapy alone, according to the biomarker data from a recent phase Ib clinical […]

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Constrained Choice and Climate Change Mitigation in US Agriculture: Structural Barriers to a Climate Change Ethic

Abstract

This paper examines structural barriers to the adoption of climate change mitigation practices and the evolution of a climate change ethic among American farmers. It examines how seed corn contracts in Michigan constrain the choices of farmers and allow farmers to rationalize the over-application of fertilizer and associated water pollution and greenhouse gas emissions. Seed corn contracts use a competitive “tournament” system where farmers are rewarded for maximizing yields. Interviews and a focus group were used to understand fertilizer over-application and barriers to participating in a climate change mitigation program. Results indicate that farmers agree that they over-apply fertilizer but would be unlikely to participate in a mitigation program due to their contracts and lack of support from seed corn companies. Because only a few companies control access to the seed corn market, farmers feel they have few choices. Farmers rationalized their practices as their only option given the competitive nature of their contracts and blamed other sources of pollution. Despite increasing efforts to educate farmers about climate change, structural barriers will continue to constrain participation in mitigation efforts and the development of a climate change ethic.

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Influenza Virus Targets Class I MHC-Educated NK Cells for Immunoevasion

journal.ppat.1005446.g001

by Ahmad Bakur Mahmoud, Megan M. Tu, Andrew Wight, Haggag S. Zein, Mir Munir A. Rahim, Seung-Hwan Lee, Harman S. Sekhon, Earl G. Brown, Andrew P. Makrigiannis

The immune response to influenza virus infection comprises both innate and adaptive defenses. NK cells play an early role in the destruction of tumors and virally-infected cells. NK cells express a variety of inhibitory receptors, including those of the Ly49 family, which are functional homologs of human killer-cell immunoglobulin-like receptors (KIR). Like human KIR, Ly49 receptors inhibit NK cell-mediated lysis by binding to major histocompatibility complex class I (MHC-I) molecules that are expressed on normal cells. During NK cell maturation, the interaction of NK cell inhibitory Ly49 receptors with their MHC-I ligands results in two types of NK cells: licensed (“functional”), or unlicensed (“hypofunctional”). Despite being completely dysfunctional with regard to rejecting MHC-I-deficient cells, unlicensed NK cells represent up to half of the mature NK cell pool in rodents and humans, suggesting an alternative role for these cells in host defense. Here, we demonstrate that after influenza infection, MHC-I expression on lung epithelial cells is upregulated, and mice bearing unlicensed NK cells (Ly49-deficient NKCKD and MHC-I-deficient B2m-/- mice) survive the infection better than WT mice. Importantly, transgenic expression of an inhibitory self-MHC-I-specific Ly49 receptor in NKCKD mice restores WT influenza susceptibility, confirming a direct role for Ly49. Conversely, F(ab’)2-mediated blockade of self-MHC-I-specific Ly49 inhibitory receptors protects WT mice from influenza virus infection. Mechanistically, perforin-deficient NKCKD mice succumb to influenza infection rapidly, indicating that direct cytotoxicity is necessary for unlicensed NK cell-mediated protection. Our findings demonstrate that Ly49:MHC-I interactions play a critical role in influenza virus pathogenesis. We suggest a similar role may be conserved in human KIR, and their blockade may be protective in humans.1LqOto9

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Correction: Structural Based Analyses of the JC Virus T-Antigen F258L Mutant Provides Evidence for DNA Dependent Conformational Changes in the C-Termini of Polyomavirus Origin Binding Domains

journal.ppat.1005482.g001

by Gretchen Meinke, Paul J. Phelan, Jong Shin, David Gagnon, Jacques Archambault, Andrew Bohm, Peter A. Bullock

1QgMRfC

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