Acute interstitial nephritis with acetaminophen and alcohol intoxication

Drug-induced acute interstitial nephritis (AIN) represents a growing cause of renal failure in current medical practice. While antimicrobials and non-steroidal anti-inflammatory drugs are typically associated with drug-induced AIN, few reports have been made on the involvement of other analgesics. We report our experience in managing a 17-year-old female with AIN and subsequent renal injury following an acetaminophen overdose in conjunction with acute alcohol intoxication. It is well established that acetaminophen metabolism, particularly at high doses, produces reactive metabolites that may induce renal and hepatic toxicity. It is also plausible however, that such reactive species could instead alter renal peptide immunogenicity, thereby inducing AIN. In the following report, we review a possible mechanism for the acetaminophen-induced AIN observed in our patient and also discuss the potential involvement of acute alcohol ingestion in disease onset. The objective of our report is to increase awareness of healthcare professionals to the potential involvement of these commonly used agents in AIN pathogenesis

Innate immunity: ignored for decades, but not forgotten.

The innate immune system must recognize and rapidly respond to microbial pathogens, providing a first line of host defense. This is accomplished through an array of pattern recognition receptors (PRRs) that reside in specific subcellular compartments and can bind pathogen-associated molecular patterns. PRRs also recognize self-molecules that are released after cell damage or death, known as danger-associated molecular patterns, which can be actively transported across cell membranes. The activation of PRRs leads to host defense pathways in infectious diseases, but can also contribute to tissue injury in autoimmune diseases. The identification of these pathways has provided new insight into mechanisms of vaccination and holds promise for developing better vaccines. Finally, the identification of PRRs, their ligands, and signaling pathways provides an opportunity for developing new immunotherapeutic approaches to skin conditions in which activation of the innate immune response contributes to disease pathogenesis

Language, People, Classrooms, World: Blending Disparate Theories for United Language Education Practices

With a forward‐looking and problem‐solving mindset, this article aims to combine theoretical knowledge and empirical evidence from different schools of thought in the field of second language (L2) learning and teaching—namely, instructed second language acquisition, generative linguistics, and an ecological perspective that includes multiple frameworks. Acknowledging numerous fundamental differences in our theoretical and methodological perspectives on how to conduct research, we are united on two fronts: First, we believe that researchers with differing theoretical commitments can and should work together to advance L2 research. Second, differing theoretical beliefs are potentially of limited relevance to those who will implement our pedagogical suggestions, that is, practitioners. In this article, we first present our individual perspectives regarding L2 learning and teaching (Perspective 1 by Michel and Sato, Perspective 2 by Alexopoulou, and Perspective 3 by Thorne and Hellermann). In the final section of the article, we unite our voices by prioritizing the educational practices upon which we agree, including the fact that all L2 learners bring their individual backgrounds into the classroom, the necessity of L2 use for L2 learning, and the role of L2 education for people\u27s overall quality of life

CT Diagnosis of an Abortion-Related Retroperitoneal Space Abscess

A female patient with a history of recent abortion was transferred in critically ill condition in our hospital. CT imaging on emergency basis depicted an abscess in the right retroperitoneal space that included the head of fetus, along with rupture of the right lateral wall of uterus. Spiral CT enabled prompt diagnosis and therapy of this rare abortion-related complication

Cover to Volume 3

The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 or NGFIB). The aim of the present study was to investigate the pathways through which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not block it. Moreover, we report that treatment with the NF-κB inhibitor BAY11-7082 suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was found to be localized in the cytoplasm and only a fraction was translocated to the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased the proliferation rate of NIH3T3 cells; however, it did not affect the chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by PDGF-BB, suppresses cell growth on a solid surface, it increases anchorage-independent growth

Immune and inflammatory responses in TNF alpha-deficient mice: A critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response

To investigate the role of TNF alpha in the development of in vivo immune response we have generated TNF alpha-deficient mice by gene targeting. Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNF alpha is not required for normal mouse development. In the absence of TNF alpha mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, TNF alpha knockout mice are resistant to the systemic toxicity of LPS upon D-galactosamine sensitization, yet they remain sensitive to high doses of LPS alone. Most interestingly, TNF alpha knockout mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell (FDC) networks and germinal centers. However, despite the absence of B cell follicles, Ig class-switching can still occur, yet deregulated humoral immune responses against either thymus-dependent (TD) or thymus-independent (TI) antigens are observed. Complementation of TNF alpha functioning by the expression of either human or murine TNF alpha transgenes is sufficient to reconstitute these defects, establishing a physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response

Future yields assessment of bioenergy crops in relation to climate change and technological development in Europe

Bioenergy crops are expected to play an important role in reducing CO2 emission, in energy supply and in European energy policy. However, a sustainable bioenergy supply must be resilient to climate change and the impacts on agriculture at both global and regional scale. The purpose of this study was to forecast the potential distribution of several bioenergy crops based on agronomic and environmental constrains under current conditions and future scenarios (2020 and 2030) in European Union. Potential biomass yield, according to the category end use product achievable in each environmental zone of Europe at present and in the future available land have been also studied. Future yields were assessed according to two factors: technological development and climate change: the former was based on prospect of DG-Agriculture for conventional crops and expert judgments for bioenergy crops, while the latter based on relevant research papers and literature reviews which used site-specific crop growth models. Yields are expected to increase in northern Europe due to climate change and technological development, while in southerneastern Europe the negative effect of climate change will be mitigated by the technological development. The estimated total biomass production in Europe, on the basis of future yields and surplus land made available for energy crops, may not be sufficient to meet the needs of bioenergy supply as claimed in the European directive 2009/28/EC

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pathogenic Mouse Hepatitis Virus or Poly(I:C) Induce IL-33 in Hepatocytes in Murine Models of Hepatitis.

International audienceThe IL-33/ST2 axis is known to be involved in liver pathologies. Although, the IL-33 levels increased in sera of viral hepatitis patients in human, the cellular sources of IL-33 in viral hepatitis remained obscure. Therefore, we aimed to investigate the expression of IL-33 in murine fulminant hepatitis induced by a Toll like receptor (TLR3) viral mimetic, poly(I:C) or by pathogenic mouse hepatitis virus (L2-MHV3). The administration of poly(I:C) plus D-galactosamine (D-GalN) in mice led to acute liver injury associated with the induction of IL-33 expression in liver sinusoidal endothelial cells (LSEC) and vascular endothelial cells (VEC), while the administration of poly(I:C) alone led to hepatocyte specific IL-33 expression in addition to vascular IL-33 expression. The hepatocyte-specific IL-33 expression was down-regulated in NK-depleted poly(I:C) treated mice suggesting a partial regulation of IL-33 by NK cells. The CD1d KO (NKT deficient) mice showed hepatoprotection against poly(I:C)-induced hepatitis in association with increased number of IL-33 expressing hepatocytes in CD1d KO mice than WT controls. These results suggest that hepatocyte-specific IL-33 expression in poly(I:C) induced liver injury was partially dependent of NK cells and with limited role of NKT cells. In parallel, the L2-MHV3 infection in mice induced fulminant hepatitis associated with up-regulated IL-33 expression as well as pro-inflammatory cytokine microenvironment in liver. The LSEC and VEC expressed inducible expression of IL-33 following L2-MHV3 infection but the hepatocyte-specific IL-33 expression was only evident between 24 to 32h of post infection. In conclusion, the alarmin cytokine IL-33 was over-expressed during fulminant hepatitis in mice with LSEC, VEC and hepatocytes as potential sources of IL-33