Evaluating the Sensitivity and Specificity of Promising Circulating Biomarkers to Diagnose Liver Injury in Humans.

Early diagnosis of drug-induced liver injury (DILI) continues to be a major hurdle during drug development and postmarketing. The objective of this study was to evaluate the diagnostic performance of promising biomarkers of liver injury-glutamate dehydrogenase (GLDH), cytokeratin-18 (K18), caspase-cleaved K18 (ccK18), osteopontin (OPN), macrophage colony-stimulating factor (MCSF), MCSF receptor (MCSFR), and microRNA-122 (miR-122) in comparison to the traditional biomarker alanine aminotransferase (ALT). Biomarkers were evaluated individually and as a multivariate model in a cohort of acetaminophen overdose (n = 175) subjects and were further tested in cohorts of healthy adults (n = 135), patients with liver damage from various causes (n = 104), and patients with damage to the muscle (n = 74), kidney (n = 40), gastrointestinal tract (n = 37), and pancreas (n = 34).

S043 mythbuster: truncal vagotomy and gastric drainage procedures.

Introduction: You are sitting for your oral surgery board exam and the examiner asks what you do when you realize that you have accidentally cut the posterior vagus nerve during a hiatal hernia repair. Is the answer to proceed with a gastric drainage procedure correct? The prevailing dogma seems to be that inadvertent vagotomy will produce gastric stasis/paresis and the stomach will not empty and hence should be accompanied by a gastric drainage procedure. This report presents clinical outcomes of 49 patients who underwent truncal vagotomy without a drainage procedure (pyloroplasty or gastrojejunostomy).

Limited Chemical Structural Diversity Found to Modulate Thyroid Hormone Receptor in the Tox21 Chemical Library.

Background: Thyroid hormone receptors (TRs) are critical endocrine receptors that regulate a multitude of processes in adult and developing organisms, and thyroid hormone disruption is of high concern for neurodevelopmental and reproductive toxicities in particular. To date, only a small number of chemical classes have been identified as possible TR modulators, and the receptors appear highly selective with respect to the ligand structural diversity. Thus, the question of whether TRs are an important screening target for protection of human and wildlife health remains.

Essential Skills for Family Medicine Residents Practicing Integrated Behavioral Health A Delphi Study.

Background And Objectives: There are several trends compelling physicians to acquire team-based skills for interprofessional care. One underdeveloped area of team-based skills for physicians is integrated behavioral health (IBH) in primary care. We used a Delphi method to explore what skills were needed for residents to practice integrated behavioral health.

Quality Control and Basics of Sterile Compounding: Attempting to Avoid Out-of-Specification Results and Patient Harm in Sterile Compounding.

What do you do when something goes wrong in your cleanroom? What do you do when a sterility test fails and what are the implications of such a failure? What should you do when your environmental monitoring or personnel monitoring provides results that exceed your action levels? A root cause analysis is needed in any situation where action levels are exceeded or tests are out of specification. However, should the questions be what can be done to prevent these occurrences, and how can the development be noticed before they occur? In this article, we will discuss going beyond the recommendations of United States Pharmacopeia Chapter <797> to attempt to build a program that limits the possibility of contamination through monitoring of the facility, personnel, and procedures in aseptic processing. We will also discuss other resources published by the U.

Basics of Sterile Compounding. Quality Assurance and Quality Control: Being Prepared for U.S. Food and Drug Administration Inspections and Staying in Compliance with United States Pharmacopeia Chapter <797>: Part 2.

Compounders engaged in making sterile preparations need to employ a quality-assurance system of documented policies and procedures to attempt to reduce the possibility of contamination. The quality-assurance program will be monitored through the facility's quality-control system. Compounders should be aware of the requirements of each state they are licensed in as well as the inspection observations commonly noted in 483s issued by the U.

Quality Assurance and Quality Control: Being Prepared for U.S. Food and Drug Administration Inspections and Staying in Compliance with United States Pharmacopeia Chapter <797>: Part 1.

Compounders engaged in making sterile preparations need to employ a quality assurance system of documented policies and procedures to attempt to reduce the possibility of contamination. The quality-assurance program will be monitored through the facility's quality control system. Compounders should be aware of the requirements of each state they are licensed in as well as the inspection observations commonly noted in 483s issued by the U.

Physician Well-Being: Physician Burnout.

Physician burnout affects patients and physicians. Recent studies estimate that more than half of all physicians in the United States currently are experiencing burnout. Burnout can include symptoms of emotional exhaustion, depersonalization, cognitive weariness, physical fatigue, and disengagement.

Basics of Sterile Compounding: Criteria for Determining Beyond-use Dating.

Compounding pharmacists must separately and collectively evaluate multiple aspects of a compounded sterile preparation when determining their beyond-use date. Considerations include the microbiological risk level, storage temperature, chemical stability, batch size, and whether or not a sterility test will be performed. The United States Pharmacopeia Chapter <797> provides guidance on the maximum beyond-use date allowed solely based on the microbiological risk level associated with the compounding of a sterile preparation.

Comparison of rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects.

Regulatory non-clinical safety testing of human pharmaceuticals typically requires embryo-fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings.

Editor's Highlight: Analysis of the Effects of Cell Stress and Cytotoxicity on In Vitro Assay Activity Across a Diverse Chemical and Assay Space.

Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Here, responses of 1060 chemicals including pharmaceuticals, natural products, pesticidals, consumer, and industrial chemicals across a battery of 815 in vitro assay endpoints from 7 high-throughput assay technology platforms were analyzed in order to distinguish between these types of activities. Both cell-based and cell-free assays showed a rapid increase in the frequency of responses at concentrations where cell stress/cytotoxicity responses were observed in cell-based assays.

Molecular Characterization and Phylogenetic Relationships of Plant-Parasitic Nematodes Associated with Turfgrasses in North Carolina and South Carolina, United States.

The near-full-length 18S ribosomal DNA (rDNA) gene and internal transcribed spacer 1 region were amplified and sequenced from 52 nematode populations belonging to 28 representative species in 13 families recovered from turfgrasses in North Carolina (38 populations) and South Carolina (14 populations). This study also included 13 nematode populations from eight other plant hosts from North Carolina for comparison. Nematodes were molecularly characterized and the phylogenetic relationships were explored based on 18S rDNA sequences.

Truncal vagotomy without drainage: Are there long-term concerns?

Introduction: Panelists at SAGES 2013 suggested that inadvertent vagotomy was the cause of the bloating, diarrhea, and delayed gastric emptying that is sometimes seen after complex foregut reconstructions that require extensive esophageal dissection. Is it correct to ascribe these symptoms to vagotomy and imply that a drainage procedure should always accompany truncal vagotomy? To examine the long-term sequelae of truncal vagotomy alone, the present report examines clinical outcomes of 49 patients who had truncal vagotomy without drainage at the time of placement of an adjustable gastric band.

Methods: Forty-nine patients underwent truncal vagotomy with laparoscopic adjustable gastric banding in an Investigational Review Board approved clinical trial to determine whether the addition of a vagotomy would increase weight loss when compared to gastric banding alone.

Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway.

The U.S. Tox21 program has screened a library of approximately 10,000 (10K) environmental chemicals and drugs in three independent runs for estrogen receptor alpha (ERα) agonist and antagonist activity using two types of ER reporter gene cell lines, one with an endogenous full length ERα (ER-luc; BG1 cell line) and the other with a transfected partial receptor consisting of the ligand binding domain (ER-bla; ERα β-lactamase cell line), in a quantitative high-throughput screening (qHTS) format.

Multi-well microelectrode array recordings detect neuroactivity of ToxCast compounds.

Spontaneous activity in neuronal cultures on microelectrode arrays (MEAs) is sensitive to effects of drugs, chemicals, and particles. Multi-well MEA (mwMEA) systems have increased throughput of MEAs, enabling their use for chemical screening. The present experiments examined a subset of EPA's ToxCast compounds for effects on spontaneous neuronal activity in primary cortical cultures using 48-well MEA plates.

Predictive endocrine testing in the 21st century using in vitro assays of estrogen receptor signaling responses.

Thousands of environmental chemicals are subject to regulatory review for their potential to be endocrine disruptors (ED). In vitro high-throughput screening (HTS) assays have emerged as a potential tool for prioritizing chemicals for ED-related whole-animal tests. In this study, 1814 chemicals including pesticide active and inert ingredients, industrial chemicals, food additives, and pharmaceuticals were evaluated in a panel of 13 in vitro HTS assays.

In vitro and modelling approaches to risk assessment from the U.S. Environmental Protection Agency ToxCast programme.

A significant challenge in toxicology is the 'too many chemicals' problem. Human beings and environmental species are exposed to tens of thousands of chemicals, only a small percentage of which have been tested thoroughly using standard in vivo test methods. This study reviews several approaches that are being developed to deal with this problem by the U.

Description of Hemicaloosia graminis n. sp. (Nematoda: Caloosiidae) Associated with Turfgrasses in North and South Carolina, USA.

A new nematode species was discovered during a diversity survey of plant-parasitic nematodes on turfgrass conducted in North and South Carolina in 2010 and 2011. It is described herein as Hemicaloosia graminis n. sp.

Diversity and Occurrence of Plant-parasitic Nematodes Associated with Golf Course Turfgrasses in North and South Carolina, USA.

One hundred and eleven golf courses from 39 counties in the Carolinas were surveyed for plant-parasitic nematodes. Species diversity within habitats was analyzed with five diversity indices including Diversity index (H'), Evenness (J'), Richness (SR), Dominance (λ) and Diversity (H2 ). The results revealed a remarkably high diversity of 24 nematode species belonging to 19 genera and 11 families.

Update on EPA's ToxCast program: providing high throughput decision support tools for chemical risk management.

The field of toxicology is on the cusp of a major transformation in how the safety and hazard of chemicals are evaluated for potential effects on human health and the environment. Brought on by the recognition of the limitations of the current paradigm in terms of cost, time, and throughput, combined with the ever increasing power of modern biological tools to probe mechanisms of chemical-biological interactions at finer and finer resolutions, 21st century toxicology is rapidly taking shape. A key element of the new approach is a focus on the molecular and cellular pathways that are the targets of chemical interactions.

Laparoscopic adjustable gastric banding with truncal vagotomy: any increased weight loss?

Background: Laparoscopic adjustable gastric banding (LAGB) causes weight loss primarily through a mechanical restrictive mechanism. The vagus nerve provides connections between the brain and the gut through afferent and hormonal signals that regulate fullness and satiety. Published studies demonstrate clinically significant weight loss by subjects undergoing open surgical truncal vagotomy for ulcer disease and morbid obesity.