Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine.

Does the Presence of a Physical Disability Affect Classification of Sexual Assault?

The occurrence of sexual assault is common and problematic, especially among those with disabilities. While many other characteristics of the victim, perpetrator, and situation involving a sexual assault have been shown to affect perceptions, only one study has examined the impact of a hypothetical victim with a physical disability. Therefore, the purpose of this study was to explore the effect that a victim and/or perpetrator's physical disability status has on individuals' classification of encounters as sexual assault.

β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.

Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing posttranslational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in mitochondria. We showed that mice with a global loss of SIRT4 [SIRT4-knockout (KO) mice] developed an increase in glucose- and leucine-stimulated insulin secretion, and this was followed by accelerated age-induced glucose intolerance and insulin resistance.

Effect of menopausal hormone therapy on proteins associated with senescence and inflammation.

Background: Estrogen may inhibit cell senescence that contributes to age-related disorders. This study determined the effects of menopausal hormone treatments on circulating levels of markers of cell senescence.

Methods: Growth differentiation factor 15 (GDF15), tumor necrosis factor receptor 1 (TNFR1), FAS, and macrophage inflammatory protein 1α (MIP1α) were measured in serum using multiplexed bead-based assays and compared among menopausal women participating in the Kronos Early Estrogen Prevention Study randomized to either placebo (n = 38), oral conjugated equine estrogen (oCEE, n = 37), or transdermal 17β-estradiol (tE2, n = 34).

Identifying incident Parkinson's disease using administrative diagnostic codes: a validation study.

Background: Administrative databases that capture diagnostic codes are increasingly being used worldwide for research because they can save time and reduce costs. However, assessing validity is necessary before defining diseases using only diagnostic codes in research applications.

Objective: Our objective was to assess the validity of using diagnostic codes to identify incident Parkinson's disease (PD) cases in Olmsted County, Minnesota using an established standard for comparison (1976-2005).

Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β Cell Metabolism in the Absence of Overnutrition.

SIRT3 is a nicotinamide adenine dinucleotide (NAD)-dependent mitochondrial protein deacetylase purported to influence metabolism through post-translational modification of metabolic enzymes. Fuel-stimulated insulin secretion, which involves mitochondrial metabolism, could be susceptible to SIRT3-mediated effects. We used CRISPR/Cas9 technology to manipulate SIRT3 expression in β cells, resulting in widespread SIRT3-dependent changes in acetylation of key metabolic enzymes but no appreciable changes in glucose- or pyruvate-stimulated insulin secretion or metabolomic profile during glucose stimulation.

Complications of Radial Column Plating of the Distal Radius.

Distal radius fractures treated with open reduction and internal fixation are commonly stabilized with a volar locking plate; however, more complex fracture patterns may require supplemental fixation with fragment-specific implants. The objective of this study was to evaluate the outcomes of distal radius fractures treated with radial column plates. A consecutive series of 61 patients who sustained distal radius fractures underwent radial column plating alone or in conjunction with other implants between August 2006 and January 2014.

Intracardiac ablation for atrioventricular nodal reentry tachycardia using a 6 mm distal electrode cryoablation catheter: Prospective, multicenter, North American study (ICY-AVNRT STUDY).

Introduction: Radiofrequency (RF) ablation is effective for slow pathway ablation, but carries a risk of inadvertent AV block requiring permanent pacing. By comparison, cryoablation with a 4-mm distal electrode catheter has not been reported to cause permanent AV block but has been shown to be less effective than RF ablation. We sought to define the safety and efficacy of a 6-mm distal electrode cryoablation catheter for slow pathway ablation in patients with atrioventricular nodal reentry tachycardia (AVNRT).

Metabolomics applied to islet nutrient sensing mechanisms.

After multiple decades of investigation, the precise mechanisms involved in fuel-stimulated insulin secretion are still being revealed. One avenue for gaining deeper knowledge is to apply emergent tools of "metabolomics," involving mass spectrometry and nuclear magnetic resonance-based profiling of islet cells in their fuel-stimulated compared with basal states. The current article summarizes recent insights gained from application of metabolomics tools to the specific process of glucose-stimulated insulin secretion, revealing 2 new mechanisms that may provide targets for improving insulin secretion in diabetes.

Characterization of health care utilization in patients receiving implantable cardioverter-defibrillator therapies: An analysis of the managed ventricular pacing trial.

Background: Implantable cardioverter-defibrillators (ICDs) are effective in terminating lethal arrhythmias, but little is known about the degree of health care utilization (HCU) after ICD therapies.

Objective: Using data from the managed ventricular pacing trial, we sought to identify the incidence and types of HCU in ICD patients after receiving ICD therapy (shocks or antitachycardia pacing [ATP]).

Methods: We analyzed HCU events (ventricular tachyarrhythmia [VTA]-related, heart failure-related, ICD implant procedure-related, ICD system-related, or other) and their association with ICD therapies (shocked ventricular tachycardia episode, ATP-terminated ventricular tachycardia episode, and inappropriately shocked episode).

SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion.

Sirtuins are NAD-dependent protein deacylases that regulate several aspects of metabolism and aging. In contrast to the other mammalian sirtuins, the primary enzymatic activity of mitochondrial sirtuin 4 (SIRT4) and its overall role in metabolic control have remained enigmatic. Using a combination of phylogenetics, structural biology, and enzymology, we show that SIRT4 removes three acyl moieties from lysine residues: methylglutaryl (MG)-, hydroxymethylglutaryl (HMG)-, and 3-methylglutaconyl (MGc)-lysine.

Delayed apoptosis allows islet β-cells to implement an autophagic mechanism to promote cell survival.

Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets.

Robot-assisted C7 nerve root transfer from the contralateral healthy side: A preliminary cadaver study.

Patients with cerebral palsy and spastic hemiplegia may have extremely poor upper extremity function. Unfortunately, many current therapies and treatments for patients with spastic hemiplegia offer very limited improvements. One innovative technique for treating these patients is the use a contralateral C7 nerve root transfer to neurotize the C7 nerve root in the affected limb.

Erratum: Distal Radius Isoelastic Resurfacing Prosthesis: A Preliminary Report.

[This corrects the article DOI: 10.1055/s-0035-1556855.].

Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells.

Insulin secretion from β cells of the pancreatic islets of Langerhans controls metabolic homeostasis and is impaired in individuals with type 2 diabetes (T2D). Increases in blood glucose trigger insulin release by closing ATP-sensitive K+ channels, depolarizing β cells, and opening voltage-dependent Ca2+ channels to elicit insulin exocytosis. However, one or more additional pathway(s) amplify the secretory response, likely at the distal exocytotic site.

Distal Radius Isoelastic Resurfacing Prosthesis: A Preliminary Report.

Background Here we present a preliminary case series of unicompartmental isoelastic resurfacing prosthesis of the distal radius to treat comminuted articular fractures of osteoporotic elderly patients. Materials and Methods Our study included 12 patients, mean age 76 years, who presented with comminuted osteoporotic distal radius fracture. Because of the severity of injury and poor bone quality; osteosynthesis was not deemed to be a good option.

SIRT3 regulates progression and development of diseases of aging.

The mitochondrial sirtuin SIRT3 is a protein deacylase that influences almost every major aspect of mitochondrial biology, including nutrient oxidation, ATP generation, reactive oxygen species (ROS) detoxification, mitochondrial dynamics, and the mitochondrial unfolded protein response (UPR). Interestingly, mice lacking SIRT3 (SIRT3KO), either spontaneously or when crossed with mouse models of disease, develop several diseases of aging at an accelerated pace, such as cancer, metabolic syndrome, cardiovascular disease, and neurodegenerative diseases, and, thus, might be a valuable model of accelerated aging. In this review, we discuss functions of SIRT3 in pathways involved in diseases of aging and how the lack of SIRT3 might accelerate the aging process.

Feedback to providers improves evidence-based implantable cardioverter-defibrillator programming and reduces shocks.

Background: Implantable cardioverter-defibrillator (ICD) shocks are associated with increased anxiety, health care utilization, and potentially mortality.

Objective: The purpose of the Shock-Less Study was to determine if providing feedback reports to physicians on their adherence to evidence-based shock reduction programming could improve their programming behavior and reduce shocks.

Methods: Shock-Less enrolled primary prevention (PP) and secondary prevention (SP) ICD patients between 2009 and 2012 at 118 study centers worldwide and followed patients longitudinally after their ICD implant.

Lysine glutarylation is a protein posttranslational modification regulated by SIRT5.

We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (Kglu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively validated by chemical and biochemical methods. We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase.

Do baseline diastolic echocardiographic parameters predict outcome after resynchronization therapy? Results from the PROSPECT trial.

Introduction: Cardiac resynchronization therapy (CRT) can improve clinical and cardiac structural status in heart failure patients. The role of baseline diastolic echocardiographic parameters to characterize the likelihood of positive outcomes is not well known. We explored relationships between diastolic parameters and outcomes 6 months after CRT implant in the Predictors of Response to CRT (PROSPECT) Trial.

Lack of current implantable cardioverter defibrillator guidelines application for primary prevention of sudden cardiac death in Latin American patients with heart failure: a cross-sectional study.

Aims: This cross-sectional study evaluated the application of accepted international implantable cardioverter defibrillator (ICD) guidelines for primary prevention of sudden cardiac death in patients with heart failure.

Methods And Results: The PLASMA (Probabilidad de Sufrir Muerte Arritmica) study was designed to characterize management of cardiac patients in Latin America. Twelve centres included 1958 consecutively admitted patients in cardiology units in 2008 and 2009.