Cell-autonomous timing drives the vertebrate segmentation clock's wave pattern.

Rhythmic and sequential segmentation of the growing vertebrate body relies on the segmentation clock, a multi-cellular oscillating genetic network. The clock is visible as tissue-level kinematic waves of gene expression that travel through the presomitic mesoderm (PSM) and arrest at the position of each forming segment. Here, we test how this hallmark wave pattern is driven by culturing single maturing PSM cells.

Impact of cost on prescribing diabetes medications for older adults with type 2 diabetes in the outpatient setting.

Background: Newer diabetes medications have cardiorenal benefits beyond blood sugar lowering that make them a preferred treatment option in many patients. Despite this, studies have shown that prescribing of these medications remains suboptimal with medication costs being hypothesized as a reason for underutilization.

Objective: To understand clinicians' decision-making processes for prescribing diabetes medications in older adults, focusing on higher cost medications.

Sonographic Assessment of Hand Injuries: Diagnostic Accuracy and Review of Pathology.

: The high soft-tissue contrast of magnetic resonance imaging (MRI) makes it useful for evaluation of hand injuries, but its limitations include cost, imaging artifacts, and patient claustrophobia. Ultrasound is readily available, fast, noninvasive, and radiation free, but its utility for the evaluation of hand soft-tissue injury and pathology is less well known. : We sought to examine the accuracy of ultrasound for the evaluation of hand injury at a single institution.

Kidney Damage and Stress Biomarkers for Early Identification of Drug-Induced Kidney Injury: A Systematic Review.

Introduction: Acute kidney injury (AKI) resulting from nephrotoxic medication use is prominent in hospitalized patients and is attributable to overall increases in mortality and costs of care. Serum creatinine (SCr), the current standard for identifying drug-induced AKI (DIAKI) is often delayed in its response to kidney insult by 26-36 h.

Objective: This systematic review seeks to evaluate the clinical utility of several novel kidney damage and stress biomarkers for the prediction/timely detection of DIAKI, in comparison with traditional methods.

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates.

A number of studies have recently shown how surface topography can alter the behavior and differentiation patterns of different types of stem cells. Although the exact mechanisms and molecular pathways involved remain unclear, a consistent portion of the literature points to epigenetic changes induced by nuclear remodeling. In this study, we investigate the behavior of clinically relevant neural populations derived from human pluripotent stem cells when cultured on polydimethylsiloxane microgrooves (3 and 10 μm depth grooves) to investigate what mechanisms are responsible for their differentiation capacity and functional behavior.

Loperamide-Induced Cardiac Events: Case Reports and Review.

Reports of cardiac arrhythmia secondary to loperamide toxicity have become increasingly common in the literature. We present two patients in their mid-20s, each having overdosed on loperamide and subsequently manifesting life-threatening cardiac arrhythmias not otherwise explained by known pathology. An analysis of the limited research available indicates that loperamide's capacity to block ion channels may be responsible for these events.

Brahma safeguards canalization of cardiac mesoderm differentiation.

Differentiation proceeds along a continuum of increasingly fate-restricted intermediates, referred to as canalization. Canalization is essential for stabilizing cell fate, but the mechanisms that underlie robust canalization are unclear. Here we show that the BRG1/BRM-associated factor (BAF) chromatin-remodelling complex ATPase gene Brm safeguards cell identity during directed cardiogenesis of mouse embryonic stem cells.

A DNA repair pathway can regulate transcriptional noise to promote cell fate transitions.

Stochastic fluctuations in gene expression ("noise") are often considered detrimental, but fluctuations can also be exploited for benefit (e.g., dither).

Dual-view light-sheet imaging through a tilted glass interface using a deformable mirror.

Light-sheet microscopy has become indispensable for imaging developing organisms, and imaging from multiple directions (views) is essential to improve its spatial resolution. We combine multi-view light-sheet microscopy with microfluidics using adaptive optics (deformable mirror) which corrects aberrations introduced by the 45-tilted glass coverslip. The optimal shape of the deformable mirror is computed by an iterative algorithm that optimizes the point-spread function in two orthogonal views.

Noise-driven cellular heterogeneity in circadian periodicity.

Nongenetic cellular heterogeneity is associated with aging and disease. However, the origins of cell-to-cell variability are complex and the individual contributions of different factors to total phenotypic variance are still unclear. Here, we took advantage of clear phenotypic heterogeneity of circadian oscillations in clonal cell populations to investigate the underlying mechanisms of cell-to-cell variability.

Quantification of pulmonary/systemic shunt ratio by single-acquisition phase-contrast cardiovascular magnetic resonance.

Purpose: Phase-contrast cardiovascular magnetic resonance (PC-CMR) quantification of intracardiac shunt (measuring the pulmonary to systemic flow ratio, Qp/Qs) is typically determined by measuring flow through planes perpendicular the pulmonary trunk (PA) and ascending aorta (Ao). This method is subject to error from presence of background velocity offsets and requires two scan acquisitions. We evaluated an alternate PC-CMR technique for quantifying Qp/Qs using a single modified plane that encompasses both the PA and Ao.

Cytoplasmic Amplification of Transcriptional Noise Generates Substantial Cell-to-Cell Variability.

Transcription is an episodic process characterized by probabilistic bursts, but how the transcriptional noise from these bursts is modulated by cellular physiology remains unclear. Using simulations and single-molecule RNA counting, we examined how cellular processes influence cell-to-cell variability (noise). The results show that RNA noise is higher in the cytoplasm than the nucleus in ∼85% of genes across diverse promoters, genomic loci, and cell types (human and mouse).

Perioperative Pain Control in the Ambulatory Setting.

Across the USA and various parts of the world, ambulatory surgery centers have transitioned to accepting patients with advanced ASA statuses, leading to a larger volume and higher complexity of surgeries performed, while still urging for same-day patient discharges. Inadequate postoperative pain management and opioid analgesia side effects, such as sedation, respiratory depression, and postoperative nausea and vomiting, are the most common complications and most common reasons for readmission after ambulatory surgery. The trend to limiting these complications and achieve a more rapid patient discharge currently emphasizes a multifactorial, balanced analgesia strategy.

Is Platelet-Rich Plasma a Future Therapy in Pain Management?

Platelet-rich plasma (PRP) has the potential to regenerate tissues and decrease pain through the effects of bioactive molecules and growth factors present in alpha granules. Several PRP preparation systems are available with varying end products, doses of growth factors, and bioactive molecules. This article presents the biology of PRP, the preparation of PRP, and the effects PRP-related growth factors have on tissue healing and repair.

Risk of Heart Failure and Death After Prolonged Smoking Cessation: Role of Amount and Duration of Prior Smoking.

Background: According to the 2004 Surgeon General's Report on Health Consequences of Smoking, after >15 years of abstinence, the cardiovascular risk of former smokers becomes similar to that of never-smokers. Whether this health benefit of smoking cessation varies by amount and duration of prior smoking remains unclear.

Methods And Results: Of the 4482 adults ≥65 years without prevalent heart failure (HF) in the Cardiovascular Health Study, 2556 were never-smokers, 629 current smokers, and 1297 former smokers with >15 years of cessation, of whom 312 were heavy smokers (highest quartile; ≥32 pack-years).

Force transmission during adhesion-independent migration.

When cells move using integrin-based focal adhesions, they pull in the direction of motion with large, ∼100 Pa, stresses that contract the substrate. Integrin-mediated adhesions, however, are not required for in vivo confined migration. During focal adhesion-free migration, the transmission of propelling forces, and their magnitude and orientation, are not understood.

Myosin II controls cellular branching morphogenesis and migration in three dimensions by minimizing cell-surface curvature.

In many cases, cell function is intimately linked to cell shape control. We used endothelial cell branching morphogenesis as a model to understand the role of myosin II in shape control of invasive cells migrating in 3D collagen gels. We applied principles of differential geometry and mathematical morphology to 3D image sets to parameterize cell branch structure and local cell-surface curvature.

Left ventricular torsion shear angle volume analysis in patients with hypertension: a global approach for LV diastolic function.

Background: Torsion shear angle φ is an important measure of left ventricular (LV) systolic and diastolic functions. Here we provide a novel index utilizing LV normalized torsion shear angle φ ^ volume V ^ loop to assess LV diastolic functional properties. We defined the area within φ ^ V ^ loop as torsion hysteresis area, and hypothesized that it may be an important global parameter of diastolic function.

Multifunctional RNA nanoparticles.

Our recent advancements in RNA nanotechnology introduced novel nanoscaffolds (nanorings); however, the potential of their use for biomedical applications was never fully revealed. As presented here, besides functionalization with multiple different short interfering RNAs for combinatorial RNA interference (e.g.

Effects of right ventricular morphology and function on outcomes of patients with degenerative mitral valve disease.

Objective: The study objective was to investigate whether, in patients undergoing surgery for degenerative mitral valve disease, associated right ventricular remodeling and dysfunction are stronger determinants of preoperative organ dysfunction and prognosis than functional tricuspid regurgitation.

Methods: From January 2001 to January 2011, 4197 patients underwent primary mitral valve surgery for degenerative valve disease at Cleveland Clinic. Using a quasi-experimental enriched study design, 781 patients were randomly selected within each grade of functional tricuspid regurgitation.

Substrates with engineered step changes in rigidity induce traction force polarity and durotaxis.

Rigidity sensing plays a fundamental role in multiple cell functions ranging from migration, to proliferation and differentiation. During migration, single cells have been reported to preferentially move toward more rigid regions of a substrate in a process termed . could contribute to cell migration in wound healing and gastrulation, where local gradients in tissue rigidity have been described.

"Stamp-off" to micropattern sparse, multicomponent features.

Spatially patterned subtractive de-inking, a process we term "stamp-off," provides a simple method to generate sparse, multicomponent protein micropatterns. It has been applied to control cell adhesion, study adhesion biology, as well as to micropattern fragile surfaces. This technique can also readily be applied to study nanoscale interactions between cell membrane receptors and surface-immobilized ligands.