Immunoaffinity proteomics for kidney injury biomarkers in male beagle dogs.

Drug-induced kidney injury (DIKI) is a cause of drug development failure. Dogs represent a common non-rodent animal model in pre-clinical safety studies; however, biomarker assays for detecting nephrotoxicity in dogs are limited. To identify novel proteins and gain insight into the molecular mechanisms involved in DIKI, we developed an assay to evaluate proteomic changes associated with DIKI in male beagle dogs that received nephrotoxic doses of tobramycin for 10 consecutive days.

Evaluation of Novel Urinary Biomarkers in Beagle Dogs With Amphotericin B-Induced Kidney Injury.

Next-generation urinary protein biomarkers have been qualified to enable monitoring for drug-induced kidney injury in toxicology studies conducted in rats. However, there is limited literature on the utility of these biomarkers in dogs. To add to the existing body of knowledge on the utility of the next-generation drug-induced kidney injury (DIKI) biomarkers, we evaluated the value of these biomarkers for the early detection of DIKI in Beagle dogs using a differentiated nephrotoxicant, Amphotericin B (AmpB).

Microaggressions: Mega problems or micro issues? A meta-analysis.

While research on microaggressions has accumulated in recent decades, doubts have arisen over their impact on individuals. Hence, the purpose of this study was to analyze the relations between microaggressions and psychological well-being, physical health, job outcomes, and positive and negative coping. Potential moderators (i.

Increasing Rate of Pulmonary Embolism in Trauma Patients at a Level One Trauma Center: An Opportunity for Quality Improvement?

Introduction Pulmonary embolism (PE) is the most common cause of preventable hospital death in trauma patients, with 100,000 patients dying from PE annually. A steadily increasing PE rate was observed over seven years in the trauma population at a single level one trauma center. Our study seeks to analyze this trend by examining risk factors and searching for targets for improvement.

How Should We Measure Social Deprivation in Orthopaedic Patients?

Background: Social deprivation negatively affects a myriad of physical and behavioral health outcomes. Several measures of social deprivation exist, but it is unclear which measure is best suited to describe patients with orthopaedic conditions.

Questions/purposes: (1) Which measure of social deprivation, defined as "limited access to society's resources due to poverty, discrimination, or other disadvantage," is most strongly and consistently correlated with patient-reported physical and behavioral health in patients with orthopaedic conditions? (2) Compared with the use of a single measure alone, how much more variability in patient-reported health does the simultaneous use of multiple social deprivation measures capture?

Methods: Between 2015 and 2017, a total of 79,818 new patient evaluations occurred within the orthopaedic department of a single, large, urban, tertiary-care academic center.

Methodological considerations for measuring biofluid-based microRNA biomarkers.

MicroRNAs (miRNAs) are small non-coding RNA that regulate the expression of messenger RNA and are implicated in almost all cellular processes. Importantly, miRNAs can be released extracellularly and are stable in these matrices where they may serve as indicators of organ or cell-specific toxicity, disease, and biological status. There has thus been great enthusiasm for developing miRNAs as biomarkers of adverse outcomes for scientific, regulatory, and clinical purposes.

Quantitative Mass Spectrometry Imaging to Study Drug Distribution in the Intestine Following Oral Dosing.

Local delivery to the lower gut to treat diseases of the colon has become a topic of special attention. Tissue exposure of locally acting agents is not represented by plasma concentrations. Therefore, reliable methods to measure tissue uptake at the primary site of action (e.

Urinary miRNA Biomarkers of Drug-Induced Kidney Injury and Their Site Specificity Within the Nephron.

Drug-induced kidney injury (DIKI) is a major concern in both drug development and clinical practice. There is an unmet need for biomarkers of glomerular damage and more distal renal injury in the loop of Henle and the collecting duct (CD). A cross-laboratory program to identify and characterize urinary microRNA (miRNA) patterns reflecting tissue- or pathology-specific DIKI was conducted.

The Utility of Novel Urinary Biomarkers in Mice for Drug Development Studies.

Novel urinary protein biomarkers have recently been identified and qualified in rats for the early detection of renal injury in drug development studies. However, there are few reports on the utility of these renal biomarkers in mice, another important and widely used preclinical animal species for drug development studies. The purpose of this study was to assess the value of these recently qualified biomarkers for the early detection of drug-induced kidney injury (DIKI) in different strains of mice using multiple assay panels.

Investigating the Value of Urine Volume, Creatinine, and Cystatin C for Urinary Biomarkers Normalization for Drug Development Studies.

Novel urinary protein biomarkers have recently been identified and qualified in rats for the early detection of renal injury in drug development studies. However, there seems to be no standardized normalization method for analyzing these urinary biomarkers, as some users normalize with urinary creatinine (uCr), urine volume (uVol), or leave biomarker un-normalized. More recently, urinary cystatin C is also emerging as a urinary biomarker normalizer, given some of its characteristics as a glomerular filtration marker.

Integrated outpatient palliative care for patients with advanced cancer: A systematic review and meta-analysis.

Background:: Despite increasing emphasis on integration of palliative care with disease-directed care for advanced cancer, the nature of this integration and its effects on patient and caregiver outcomes are not well-understood.

Aim:: We evaluated the effects of integrated outpatient palliative and oncology care for advanced cancer on patient and caregiver outcomes.

Design:: Following a standard protocol (PROSPERO: CRD42017057541), investigators independently screened reports to identify randomized controlled trials or quasi-experimental studies that evaluated the effect of integrated outpatient palliative and oncology care interventions on quality of life, survival, and healthcare utilization among adults with advanced cancer.

Brief Overview: Assessment of Compound-induced Acute Kidney Injury Using Animal Models, Biomarkers, and In Vitro Platforms.

The inability to unequivocally predict translatable drug-induced kidney injury in nonclinical studies during pharmacological development is evidenced by drug attrition in human clinical trials. Eight urinary proteins have been qualified as renal safety biomarkers for limited context of use in nonclinical drug development studies in rats. Formal qualification of human renal safety biomarkers is pending the submission of data from prospective clinical trials and analyses of biomarker performance to the Food and Drug Administration and European Medicines Agency by the Foundation for the National Institutes of Health and Predictive Safety Testing Consortium's Nephrotoxicity Working Group.

Interventions That Support or Involve Caregivers or Families of Patients with Traumatic Injury: a Systematic Review.

Background: Almost 40 million family caregivers care for a loved one with severe physical or cognitive impairments. The purpose of this review is to summarize evidence about the benefits of interventions to support or involve family members/caregivers of patients with trauma-related injury on caregiver, patient, and household outcomes.

Methods: English-language peer-reviewed publications in MEDLINE, CINAHL, and PsycINFO from 1995 through December 2016 were identified.

Management of Menopause Symptoms with Acupuncture: An Umbrella Systematic Review and Meta-Analysis.

Objectives: Vasomotor symptoms (VMSs) are the most common symptoms reported during menopause. Although hormone therapy is effective for reducing VMSs, its use is restricted in some women. Many women with VMSs thus seek nonhormonal, nonpharmacologic treatment options such as acupuncture.

Improving vasomotor symptoms; psychological symptoms; and health-related quality of life in peri- or post-menopausal women through yoga: An umbrella systematic review and meta-analysis.

Objectives: Vasomotor symptoms (VMS), commonly reported during menopausal transition, negatively affect psychological health and health-related quality of life (HRQoL). While hormone therapy is an effective treatment, its use is limited by concerns about possible harms. Thus, many women with VMS seek nonhormonal, nonpharmacologic treatment options.

Evaluation of Temporal Changes in Urine-based Metabolomic and Kidney Injury Markers to Detect Compound Induced Acute Kidney Tubular Toxicity in Beagle Dogs.

Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin- induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urinebased metabolomic fingerprint.

LC/MS/MS Profiling of Tissue Oxysterols and its Application in Dextran Sodium Sulphate Induced Mouse Colitis Models.

We have developed a workflow to extract, separate, and semi-quantify bioactive oxysterols from mouse colon tissues and fecal matters using solid- and liquid-phase extractions, enzymatic and chemical modifications, and stable-isotope dilution LC/MS/MS. The method was applied to a dextran sodium sulphate (DSS)-induced mouse colitis model, which revealed that one particular dihydroxycholesterol (diOHC), 7α,25-diOHC, was significantly elevated in both colon tissue and fecal matters of mice with colitis compared to that in naïve mice. The extent of 7α,25-diOHC elevation was positively correlated with colitis severity.