Resident Feedback on Incorporating Reflection Rounds Into a Family Medicine Residency Wellness Curriculum: A Brief Report.

Background: We sought to understand well-being from the perspectives of residents in a family medicine residency program and to assess the residents' opinions on implementing "Reflection Rounds" (RR) to promote wellness and combat burnout through self-reflection. These aims were achieved through descriptive qualitative analysis of a focus group of family medicine residents.

Methods: Participation was voluntary and open to all 45 residents in the program.

Cell Membrane Transporters Facilitate the Accumulation of Hepatocellular Flucloxacillin Protein Adducts: Implication in Flucloxacillin-Induced Liver Injury.

Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver reactions. Although expression of HLA-B*57:01 increases susceptibility, little is known about the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the presentation of flucloxacillin-modified peptides by the risk allele.

CDDO-imidazolide Targets Multiple Amino Acid Residues on the Nrf2 Adaptor, Keap1.

Synthetic triterpenoids including CDDO, its methyl ester (CDDO-Me, bardoxolone methyl), and its imidazolide (CDDO-Im) enhance Nrf2-mediated antioxidant and anti-inflammatory activity in many diseases by reacting with thiols on the adaptor protein, Keap1. Unlike monofunctional CDDO-Me, the bifunctional analog, CDDO-Im, has a second reactive site (imidazolide) and can covalently bind to amino acids other than cysteine on target proteins such as glutathione S-transferase pi (GSTP), serum albumin, or Keap1. Here we show for the first time that bifunctional CDDO-Im (in contrast to CDDO-Me), as low as 50 nM, can covalently transacylate arginine and serine residues in GSTP and cross-link them to adjacent cysteine residues.

Identification of Flucloxacillin-Haptenated HLA-B*57:01 Ligands: Evidence of Antigen Processing and Presentation.

Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver reactions. Although expression of human leukocyte antigen (HLA)-B*57:01 increases susceptibility, little is known of the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the modification of peptides that are presented by the risk allele.

Definition of Haptens Derived from Sulfamethoxazole: In Vitro and in Vivo.

Hypersensitivity reactions occur frequently in patients upon treatment with sulfamethoxazole (SMX). These adverse effects have been attributed to nitroso sulfamethoxazole (SMX-NO), the reactive product formed from auto-oxidation of the metabolite SMX hydroxylamine. The ability of SMX-NO to prime naïve T-cells in vitro and also activate T-cells derived from hypersensitive patients has illustrated that T-cell activation may occur through the binding of SMX-NO to proteins or through the direct modification of MHC-bound peptides.

Agricultural costs of the Chesapeake Bay total maximum daily load.

This study estimates costs to agricultural producers of the Watershed Implementation Plans (WIPs) developed by states in the Chesapeake Bay Watershed to comply with the Chesapeake Bay total maximum daily load (TMDL) and potential cost savings that could be realized by a more efficient selection of agricultural Best Management Practices (BMPs) and spatial targeting of BMP implementation. The cost of implementing the WIPs between 2011 and 2025 is estimated to be about $3.6 billion (in 2010 dollars).

Hepatic activation of irinotecan predicts tumour response in patients with colorectal liver metastases treated with DEBIRI: exploratory findings from a phase II study.

Purpose: The response of colorectal liver metastases to the cytotoxic agent irinotecan varies widely. Attempts to correlate tumour metabolism with response have been mixed. This study investigated the hepatic metabolism of irinotecan as a potential predictor of tumour response to irinotecan-eluting beads (DEBIRI).

β-Lactam antibiotics form distinct haptenic structures on albumin and activate drug-specific T-lymphocyte responses in multiallergic patients with cystic fibrosis.

β-Lactam antibiotics provide the cornerstone of treatment for respiratory exacerbations in patients with cystic fibrosis. Unfortunately, approximately 20% of patients develop multiple nonimmediate allergic reactions that restrict therapeutic options. The purpose of this study was to explore the chemical and immunological basis of multiple β-lactam allergy through the analysis of human serum albumin (HSA) covalent binding profiles and T-cell responses against 3 commonly prescribed drugs; piperacillin, meropenem, and aztreonam.

Integrated watershed- and farm-scale modeling framework for targeting critical source areas while maintaining farm economic viability.

Quantitative risk assessments of pollution and data related to the effectiveness of mitigating best management practices (BMPs) are important aspects of nonpoint source pollution control efforts, particularly those driven by specific water quality objectives and by measurable improvement goals, such as the total maximum daily load (TMDL) requirements. Targeting critical source areas (CSAs) that generate disproportionately high pollutant loads within a watershed is a crucial step in successfully controlling nonpoint source pollution. The importance of watershed simulation models in assisting with the quantitative assessments of CSAs of pollution (relative to their magnitudes and extents) and of the effectiveness of associated BMPs has been well recognized.

Living above the shop: home, business, and family in the English "Industrial Revolution".

This article explores the living arrangements and familial relations of small business households in northwest English towns between 1760 and 1820. Focusing on evidence from inventories and personal writing, it examines the homes that such households lived and worked in and the ways in which space was ordered and used: indicating that access to particular spaces was determined by status. This study suggests both the continuance of the "household family" into the nineteenth century (rather than its more modern, "nuclear" variant) and the existence of keenly felt gradations of status within households making it likely that the constitution of "the family" differed according to one's place in the domestic hierarchy.

Glutathione-S-transferase pi as a model protein for the characterisation of chemically reactive metabolites.

Chemically reactive metabolites (CRMs) are thought to be responsible for a number of adverse drug reactions through modification of critical proteins. Methods that defined the chemistry of protein modification at an early stage would provide invaluable tools for drug safety assessment. Here, human GST pi (GSTP) was exploited as a model target protein to determine the chemical, biochemical and functional consequences of exposure to the hepatotoxic CRM of paracetamol (APAP), N-acetyl-p-benzoquinoneimine (NAPQI).

Economic and phosphorus-related effects of precision feeding and forage management at a farm scale.

Structural best management practices were implemented throughout the Cannonsville Reservoir Watershed (CRW) in an effort to reduce P losses to the reservoir. Yet long-term water quality control efforts within CRW are hindered by continuous P build-up in the soils resulting from dairy farm P imports exceeding exports. Addressing the P imbalance problems and maintaining economic viability of the farms requires a system-level redesign of farm management.

The topoisomerase II-Hsp90 complex: a new chemotherapeutic target?

The modulation of DNA topology by topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and has thus become a highly attractive target for chemotherapeutic drugs. However, these drugs are highly toxic, and so new approaches are required. One such strategy is to target topoisomerase II-interacting proteins.

Protein phosphatase 2A, a negative regulator of the ERK signaling pathway, is activated by tyrosine phosphorylation of putative HLA class II-associated protein I (PHAPI)/pp32 in response to the antiproliferative lectin, jacalin.

Protein phosphatase 2A (PP2A) is a family of mammalian serine/threonine phosphatases that is involved in the control of many cellular functions including those mediated by extracellular signal-regulated kinase (ERK) signaling. While investigating the reversible antiproliferative effect of the dietary lectin, jacalin, which binds the Thomsen-Friedenreich antigen (galactose beta1-3 N-acetylgalactosamine alpha-), we have found that this lectin (30 microg/ml) induces rapid, transient, tyrosine phosphorylation of putative human HLA-DR-associated protein I (PHAPI, also known as the tumor suppressor pp32) in HT29 human colon cancer cells. This is accompanied by the release of PP2A from association with PHAPI, allowing increased phosphatase activity of PP2A (by 42 +/- 10% at 10 min) and consequent complete dephosphorylation of the ERK kinase, MEK1/2, by 10 min and of ERK1/2 by 60 min.

Application of laser capture microdissection combined with two-dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal of all the common malignancies and markers for early detection or targets for treatment of this disease are urgently required. The disease is characterised by a strong stromal response, with cancer cells usually representing a relatively small proportion of the cells in the tumor mass. We therefore performed laser capture microdissection (LCM) to enrich for both normal and malignant pancreatic ductal epithelial cells.

Protein expression profiling of glutathione S-transferase pi null mice as a strategy to identify potential markers of resistance to paracetamol-induced toxicity in the liver.

GST pi (GSTP) is a member of the glutathione S-transferase (EC 2.5.1.

Regulation of growth factor induced gene expression by calcium signalling: integrated mRNA and protein expression analysis.

There is considerable indirect evidence that growth factor induced changes in the intracellular concentration of calcium play an important role in the regulation of the mammalian cell cycle. However, the precise mechanism by which this may be achieved remains unclear. Here we show that SKF-96365, an inhibitor of growth factor induced capacitative calcium entry (CCE), inhibits cell cycle progression by preventing entry into S phase.

Universal newborn hearing screening with automated auditory brainstem response: a multisite investigation.

Objective: The purpose of the study was to assess the feasibility of performing universal newborn hearing screening in different clinical settings and tracking the infants who did not pass initial screening through their confirmatory testing.

Study Design: Between December 1996 and December 1997, a total of 11,711 infants were enrolled from five clinically different study sites. Universal newborn hearing screening was performed using automated auditory brainstem response (AABR) testing.

Mastoparan transiently permeabilizes Swiss 3T3 cells and induces c-fos proto-oncogene expression. Role of calcium and G protein activation.

Mastoparan, a widely used tetradecapeptide activator of Gi/Go G proteins, has been reported to be a potent co-mitogen for Swiss 3T3 fibroblasts. However, we have previously shown that the peptide promotes the release of lactate dehydrogenase from Swiss 3T3 cells and evokes only a modest and delayed increase in DNA. We suggested that the ability of the peptide to permeabilise these cells may account for its mitogenic action.

Inhibition of mitogen-induced DNA synthesis by bafilomycin A1 in Swiss 3T3 fibroblasts.

Quiescent cells (in G0) can be stimulated to enter the cell cycle and proceed to DNA synthesis in S-phase by a wide range of growth factors and mitogens. Activation of cell-surface growth factor receptors with intrinsic protein tyrosine kinase activity initiates autophosphorylation of the receptors and subsequent activation of signal transduction cascades. After activation the receptors undergo ligand-induced internalization to endosomes, which become acidified by the action of a vacuolar H(+)-ATPase (V-ATPase).

[Density of rapid eye movements during active sleep in preterm newborn infants].

Rapid eye movement (REM) density has been helpful as a reliable index of phasic eye movements activity during REM (active) sleep in adults. We evaluated this index in 28 newborns, at 34 to 39 weeks of conceptional age (CA). The 5 hours polysomnographic recording during sleep included electroencephalogram, electrooculogram, electrocardiogram, pneumogram, nasal thermistor for detecting airflow, and continuous oxygen saturation (tcPO2) monitoring.