Effects of antimicrobial use in agricultural animals on drug-resistant foodborne salmonellosis in humans: A systematic literature review

Controversy continues concerning antimicrobial use in food animals and its relationship to drug-resistant infections in humans. We systematically reviewed published literature for evidence of a relationship between antimicrobial use in agricultural animals and drug-resistant meat or dairy-borne non-typhoidal salmonellosis in humans. Based on publications from the United States (U.S.), Canada, and Denmark from January 2010 to July 2014, 858 articles received title and abstract review, 104 met study criteria for full article review with 68 retained for which data are presented. Antibiotic exposure in both cattle and humans found an increased likelihood of Salmonella colonization, whereas in chickens, animals not exposed to antibiotics (organic) were more likely to be Salmonella positive and those that had antibiotic exposure were more likely to harbor antimicrobial resistant Salmonella organisms. In swine literature, only tylosin exposure was examined and no correlation was found among exposure, Salmonella colonization, or antimicrobial resistance. No studies that identified farm antimicrobial use also traced antimicrobial-resistant Salmonella from farm to fork.     

Divergent Synthesis of Novel Cylindrocyclophanes that Inhibit Methicillin-Resistant Staphylococcus aureus (MRSA)

The cylindrocyclophanes are a family of macrocyclic natural products reported to exhibit antibacterial activity. Little is known about the structural basis of this activity due to the challenges associated with their synthesis or isolation. We hypothesised that structural modification of the cylindrocyclophane scaffold could streamline their synthesis without significant loss of activity. Herein, we report a divergent synthesis of the cylindrocyclophane core enabling access to symmetrical macrocycles by means of a catalytic, domino cross-metathesis-ring-closing metathesis cascade, followed by late-stage diversification. Phenotypic screening identified several novel inhibitors of methicillin-resistant Staphylococcus aureus. The most potent inhibitor has a unique tetrabrominated [7,7]paracyclophane core with no known counterpart in nature. Together these illustrate the potential of divergent synthesis using catalysis and unbiased screening methods in modern antibacterial discovery.     

TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation

TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation.     

The Australian brushtail possum (Trichosurus vulpecula) gonadotrophin alpha-subunit: analysis of cDNA sequence and pattern of expression

Substantial evidence has accumulated to suggest that in the near future implementation of the veto-cell-suppressor concept in the treatment of kidney allograft recipients might lead to the establishment of life-long specific allograft tolerance in the absence of further immunosuppressive therapy. Veto suppression prevents the generation of antigen-specific T-helper and cytotoxic T lymphocytes in vitro provided that the T-lymphocyte precursors specifically recognize antigenic peptides associated with the major histocompatibility complex molecules class II and class I, respectively, expressed on the surface of the veto-active cell. Data from a large number of experimental and clinical studies strongly indicate that veto-active cells function in vivo and are capable of preventing allograft rejection. Thus, donor-cell-mediated veto activity is the most likely explanation for the well-known graft tolerizing effect of pretransplant donor blood transfusions in kidney graft recipients. A prerequisite for a veto-active environment in vivo is the establishment of lymphoid microchimerism, in which veto-active donor and recipient cells mutually downregulate potential alloaggression.     

Transient blindness associated with reversible occipital white matter abnormalities: two patients studied by MR, CT, and 18F-FDG PET imaging

We report the case of a patient with mycosis fungoides, stage II B with generalized plaques and ulcerated tumors in a severely reduced general condition, with anemia and extremely poor compliance, who was successfully treated with total-skin electron-beam radiotherapy with a less severe relapse after more than three years.     

Intracellular localisation of urea-cycle enzymes in liver (author's transl)

Enzymes of the Krebs-Henseleit urea-cycle were localized by means of differential centrifugation and fractional tissue extraction in rat liver and in human liver. Argininosuccinatlyase (ASAL) and Argininosuccinatsynthetase (ASAS) represent enzymes of the soluble cytoplasmic fraction. Ornithine-ketoacid-transaminase(OKT), carbamyl-phosphate-synthetase (CPS) and ornithine-carbamyl-transferase (OCT) are localized in the mitochondrial and nuclei fractions of the liver cell. Most of the arginase activity is bound to subcellular structures (probably to nuclei). A small portion of arginase-activity was found in the soluble cytoplasmatic fraction. The enzymes of the Krebs-Henseleit urea-cycle are equally distributed in rat liver and in human liver. Differences in the subcellular localisation of (mitochondrial) enzymes in human liver could be attributed to mitochondrial breakage during tissue preparation and do not represent in-vivo conditions.     

Are brook trout streams in western Virginia and Shenandoah National Park recovering from acidification?

Streamwater composition data obtained through periodic sampling of streams that support brook trout (Salvelinus fontinalis) in the mountains of western Virginia were examined for evidence of recovery from acidification during the 1988-2001 period. Measurements of sulfate deposition in precipitation indicate that sulfate deposition in the region declined approximately 40% between 1985 and 2000. While no significant regional trends in acid-base constituents were observed for the set (n = 65) of western Virginia study streams, significant regional trends were observed for a subset (n = 14) of streams in Shenandoah National Park (SNP). For the subset of SNP streams, the median increase in acid-neutralizing capacity (ANC) was 0.168 microequiv L(-1) year(-1) and the median decrease in sulfate concentration was -0.229 microequiv L(-1) year(-1). Although these trends are consistent with recovery from acidification, the degree of apparent recovery is small compared to estimates of historic acidification in SNP streams and much less than observed in other, more northern regions in the United States. Correlation between sulfate concentration trends and current sulfate concentrations in streamwater suggests that recovery from stream acidification in the western Virginia region is determined by sulfur retention processes in watershed soils. A transient increase in nitrate concentrations that occurred among some western Virginia streams following forest defoliation by the gypsy moth (Lymantria dispar) complicates interpretation of the observed patterns of change in acid-base status.