175 years of bilirubin testing : ready for point-of-care?

Bilirubin was first detected in blood in 1847 and since then has become one of the most widely used biomarkers for liver disease. Clinical routine bilirubin testing is performed at the hospital laboratory, and the gold standard colorimetric test is prone to interferences. The absence of a bedside test for bilirubin delays critical clinical decisions for patients with liver disease. This clinical care gap has motivated the development of a new generation of bioengineered point-of-care bilirubin assays. In this Perspective, recently developed bilirubin assays are critically discussed, and their translational potential evaluated

Telomeres and replicative cellular aging of the human placenta and chorioamniotic membranes

Recent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births

Comparison of gadolinium-based contrast agents for MR cholangiography in saline, blood and bile: a phantom study

Abstract Background We compared T1- and T2-weighted signal intensities of liver-specific (gadoxetate, gadobenate) and non-specific (gadoterate) gadolinium contrast agents (CAs) in a bile phantom. Methods In a phantom study, gadoxetate, gadobenate, and gadoterate were diluted in saline, blood, and bile at different concentrations (0, 0.25, 0.5. 1, 2.5, 5, 10, and 25 mM) and imaged in a 3-T magnetic resonance imaging (MRI) system using T1- and T2-weighted sequences. The maximum signal intensities of CAs were compared for each sequence separately and across all T1-weighted sequences using one-way ANOVA. Results Using T1-weighted sequences, CA concentration-dependent signal intensity increase was followed by decrease due to T2* effects. Comparing CAs for each sequence in bile yielded higher maximum signal intensities with gadobenate than gadoxetate and gadoterate using T1-weighted spin-echo (p  0.141). Signal reduction with CA concentration-dependent decrease was observed on T2-weighted images. Conclusion In this bile phantom study of gadolinium-based CA, gadobenate and gadoxetate showed high signal intensity with T1-weighted TFE and 3D-mFFE sequences, which supports their potential utility for contrast-enhanced hepatobiliary MRI. Key points • Contrast-enhanced magnetic resonance (MR) cholangiography depends on contrast agent type, kinetics, and concentration in bile, • We compared signal intensities of three contrast agents in a bile phantom study. • Gadobenate, gadoxetate, and gadoterate demonstrated different signal intensities at identical concentrations. • Gadoxetate and gadobenate showed high signal intensities on T1-weighted MR sequences

Pharmacists as Personalized Medicine Experts (PRIME): Experiences Implementing Pharmacist-Led Pharmacogenomic Testing in Primary Care Practices

Research exploring the integration of pharmacogenomics (PGx) testing by pharmacists into their primary care practices (including community pharmacies) has focused on the “external” factors that impact practice implementation. In this study, additional “internal” factors, related to the capabilities, opportunities, and motivations of pharmacists that influence their ability to implement PGx testing, were analyzed. Semi-structured interview data from the Pharmacists as Personalized Medicine Experts (PRIME) study, which examined the barriers and facilitators to implementing PGx testing by pharmacists into primary care practice, were analyzed. Through thematic analysis, using the theoretical domains framework (TDF) domains as deductive codes, the authors identified the most relevant TDF domains and applied the behavioural change wheel (BCW) to generate intervention types to aid in the implementation of PGx testing. Pharmacists described how their professional identities, practice environments, self-confidence, and beliefs in the benefits of PGx impacted their ability to provide a PGx-testing service. Potential interventions to improve the implementation of the PGx service included preparing pharmacists for managing an increased patient load, helping pharmacists navigate the software and technology requirements associated with the PGx service, and streamlining workflows and documentation requirements. As interest in the wide-scale implementation of PGx testing through community pharmacies grows, additional strategies need to address the “internal” factors that influence the ability of pharmacists to integrate testing into their practices

Telomere length dynamics in early life: the blood‐and‐muscle model

International audienceTelomere length (TL) trajectories in somatic tissues during human growth and development are poorly understood. We examined a blood-and-muscle model during early life, focusing on TL trajectories in leukocytes, representing the highly proliferative hematopoietic system, and skeletal muscle, a minimally proliferative tissue. Leukocyte TL (LTL) and skeletal muscle TL (MTL) were measured in 28 fetuses and 73 children. LTL and MTL were highly variable across individuals (sd: fetal LTL = 0.72 kb, MTL = 0.72 kb; children LTL = 0.81 kb, MTL = 0.82 kb) but were highly correlated within individuals (fetuses, r = 0.76, P < 0.0001; children, r = 0.87, P < 0.0001). LTL was shorter than MTL in fetuses (10.63 vs. 11.01 kb; P = 0.0004) and children (8.46 vs. 9.40 kb; <0.0001). The LTL-MTL gap was smaller in fetuses than children. TL in children was inversely correlated with body mass index (BMI) (LTL: -0.047 ± 0.016 kb/BMI, P < 0.005; MTL: -0.037 ± 0.017 kb/BMI, P = 0.03). We conclude that variations in TL across adults and differences in TL between somatic tissues are largely established in early life. Because TL plays a significant role in aging-related diseases, insight into the factors that fashion TL in somatic tissues during early development should contribute to an understanding of the relationship of TL with these disease and longevity in humans.-Sabharwal, S., Verhulst, S., Guirguis, G., Kark, J. D., Labat, C., Roche, N. E., Martimucci, K., Patel, K., Heller, D. S., Kimura, M., Chuang, D., Chuang, A., Benetos, A., Aviv, A. Telomere length dynamics in early life: the blood-and-muscle model

Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation: A Proposal for Standardization in Fellowship and Training Programs.

The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation

Discovery-based science education: functional genomic dissection in Drosophila by undergraduate researchers.

How can you combine professional-quality research with discovery-based undergraduate education? The UCLA Undergraduate Consortium for Functional Genomics provides the answe