Depletion of penicillin G residues in sows after intramuscular injection

A penicillin G procaine residue depletion study was conducted in heavy sows to estimate the pre-slaughter withdrawal periods necessary to clear penicillin from kidney and muscle. Heavy sows (n=126) were treated with penicillin G procaine at a 5x dose (33,000 IU/kg) for 3 consecutive days by intramuscular (IM) injection using 3 separate patterns of drug administration. Treatments differed by pattern and volume of penicillin G procaine administration. Sets of 6 animals per treatment were each slaughtered with 5, 10, 15, 20, 25, 32, and 39 day withdrawal periods; skeletal muscle and kidney were collected for penicillin G analysis by LC-MS/MS. Penicillin residues in skeletal muscle averaged 23.5 ± 10.5 ng/g at withdrawal day 5 for all treatments, but averaged 3,760 ± 1,930 ppb in kidney

Evaluation of penicillin G residues by kidney inhibition swab tests in sow body fluids and tissues following intramuscular injection

In 2011, the USDA-Food Safety and Inspection Service (FSIS) changed the method used for screening swine tissues for antimicrobial residues from the Fast Antimicrobial Screen Test to the Kidney Inhibition Swab (KIS™). Here, we describe the use of KIS™ test for the detection of penicillin G residues in kidney, liver, plasma, urine, and skeletal muscle of heavy sows following the administration of a 5x label dose of penicillin G procaine. Such off-label use is legal in the United States under the Animal Medicinal Drug Use Clarification Act (AMDUCA) when label routes or doses are ineffective at treating disease and is commonly used to treat bacterial infections in heavy sows

Random Spiking and Systematic Evaluation of Defenses Against Adversarial Examples

Image classifiers often suffer from adversarial examples, which are generated by strategically adding a small amount of noise to input images to trick classifiers into misclassification. Over the years, many defense mechanisms have been proposed, and different researchers have made seemingly contradictory claims on their effectiveness. We present an analysis of possible adversarial models, and propose an evaluation framework for comparing different defense mechanisms. As part of the framework, we introduce a more powerful and realistic adversary strategy. Furthermore, we propose a new defense mechanism called Random Spiking (RS), which generalizes dropout and introduces random noises in the training process in a controlled manner. Evaluations under our proposed framework suggest RS delivers better protection against adversarial examples than many existing schemes.Comment: To be appear in ACM CODESPY 202

Selective Sweep Analysis in the Genomes of the 91-R and 91-C Drosophila melanogaster Strains Reveals Few of the ‘Usual Suspects’ in Dichlorodiphenyltrichloroethane (DDT) Resistance

Adaptation of insect phenotypes for survival after exposure to xenobiotics can result from selection at multiple loci with additive genetic effects. To the authors’ knowledge, no selective sweep analysis has been performed to identify such loci in highly dichlorodiphenyltrichloroethane (DDT) resistant insects. Here we compared a highly DDT resistant phenotype in the Drosophila melanogaster (Drosophila) 91-R strain to the DDT susceptible 91-C strain, both of common origin. Whole genome re-sequencing data from pools of individuals was generated separately for 91-R and 91-C, and mapped to the reference Drosophila genome assembly (v. 5.72). Thirteen major and three minor effect chromosome intervals with reduced nucleotide diversity (π) were identified only in the 91-R population. Estimates of Tajima\u27s D (D) showed corresponding evidence of directional selection in these same genome regions of 91-R, however, no similar reductions in π or D estimates were detected in 91-C. An overabundance of non-synonymous proteins coding to synonymous changes were identified in putative open reading frames associated with 91-R. Except for NinaC and Cyp4g1, none of the identified genes were the ‘usual suspects’ previously observed to be associated with DDT resistance. Additionally, up-regulated ATP-binding cassette transporters have been previously associated with DDT resistance; however, here we identified a structurally altered MDR49 candidate resistance gene. The remaining fourteen genes have not previously been shown to be associated with DDT resistance. These results suggest hitherto unknown mechanisms of DDT resistance, most of which have been overlooked in previous transcriptional studies, with some genes having orthologs in mammals

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Clinical Usefulness of Measuring Red Blood Cell Distribution Width in Patients with Hepatitis B

BACKGROUND: Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity (e.g., anisocytosis) that is largely overlooked, is a newly recognized risk marker in patients with cardiovascular diseases, but its role in persistent viral infection has not been well-defined. The present study was designed to investigate the association between RDW values and different disease states in hepatitis B virus (HBV)-infected patients. In addition, we analyzed whether RDW is associated with mortality in the HBV-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and twenty-three patients, including 16 with acute hepatitis B (AHB), 61 with chronic hepatitis B (CHB), and 46 with chronic severe hepatitis B (CSHB), and 48 healthy controls were enrolled. In all subjects, a blood sample was collected at admission to examine liver function, renal function, international normalized ratio and routine hematological testing. All patients were followed up for at least 4 months. A total of 10 clinical chemistry, hematology, and biochemical variables were analyzed for possible association with outcomes by using Cox proportional hazards and multiple regression models. RDW values at admission in patients with CSHB (18.30±3.11%, P<0.001), CHB (16.37±2.43%, P<0.001) and AHB (14.38±1.72%, P<0.05) were significantly higher than those in healthy controls (13.03±1.33%). Increased RDW values were clinically associated with severe liver disease and increased 3-month mortality rate. Multivariate analysis demonstrated that RDW values and the model for end-stage liver disease score were independent predictors for mortality (both P<0.001). CONCLUSION: RDW values are significantly increased in patients with hepatitis B and associated with its severity. Moreover, RDW values are an independent predicting factor for the 3-month mortality rate in patients with hepatitis B

Transcriptional Responses of Leptospira interrogans to Host Innate Immunity: Significant Changes in Metabolism, Oxygen Tolerance, and Outer Membrane

Leptospirosis is an important tropical disease around the world, particularly in humid tropical and subtropical countries. As a major pathogen of this disease, Leptospira interrogans can be shed from the urine of reservoir hosts, survive in soil and water, and infect humans through broken skin or mucous membranes. Recently, host adaptability and immune evasion of L. interrogans to host innate immunity was partially elucidated in infection or animal models. A better understanding of the molecular mechanisms of L. interrogans in response to host innate immunity is required to learn the nature of early leptospirosis. This study focused on the transcriptome of L. interrogans during host immune cells interaction. Significant changes in energy metabolism, oxygen tolerance and outer membrane protein profile were identified as potential immune evasion strategies by pathogenic Leptospira during the early stage of infection. The major outer membrane proteins (OMPs) of L. interrogans may be regulated by the major OmpR specific transcription factor (LB333). These results provide a foundation for further studying the pathogenesis of leptospirosis, as well as identifying gene regulatory networks in Leptospira spp

Beyond the leftward limit of the perceptual span: Parafoveal processing to the left of fixation in Chinese reading.

During reading, Chinese readers have been found to obtain useful visual information from one character to the left to three characters to the right of fixation. The perceptual span is asymmetrical, and its leftward extent seems to be limited compared with the rightward extent. We conducted an experiment to investigate whether Chinese readers could process written information beyond the leftward extent of the perceptual span. We did this by using a variation of the gaze-contingent display change paradigm (Rayner, Cognitive Psychology, 81, 65-81, 1975) in order to manipulate the parafoveal "postview" that was available to the left of where readers were fixating. Each sentence contained an invisible boundary. Once the readers' eyes crossed the boundary, all of the characters to the left of the boundary except for one, two, or three characters directly to the left of the boundary were replaced with visually similar characters. The change lasted for only one single fixation, resulting in four different "postview" conditions including a control condition (n - 1, n - 2, n - 3, control). The results showed that, compared with the control condition, there were more regressions to the display change area immediately after readers' eyes crossed the boundary in the n - 1, n - 2, and n - 3 conditions, demonstrating that readers can acquire information from the three characters to the left of fixation at least