Association between plasma concentrations of vitamin D metabolites and depressive symptoms throughout pregnancy in a prospective cohort of Brazilian women.

Plasma concentrations of vitamin D metabolites can be inversely associated with depressive symptoms. However, few longitudinal studies have investigated this association, especially during pregnancy. The aim of this study was to investigate the association between concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxivitamin D [1,25(OH)D] with the occurrence of depressive symptoms throughout pregnancy.

Valvular Heart Disease in Adults: Management of Prosthetic Heart Valves.

Patients undergoing cardiac valve replacement may receive mechanical or bioprosthetic valves. Mechanical valves require lifelong anticoagulation but are durable and the need for a second surgery is up to eightfold times less than with bioprosthetic valves. Bioprosthetic valves do not require lifelong anticoagulation and thus are associated with fewer bleeding complications but they are less durable and associated with higher morbidity and mortality rates, particularly in younger patients.

iGlarLixi: A Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide for the Treatment of Type 2 Diabetes.

Objective: To review the safety and efficacy of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, a glucagon-like peptide-1 receptor agonist.

Data Sources: A literature search of MEDLINE for all English-language primary articles through June 2016, using the terms LixiLan, iGlarLixi and insulin glargine and lixisenatide, and a search of abstracts presented at the 2016 Scientific Sessions of the American Diabetes Association were performed.

Study Selection And Data Extraction: All studies assessing the efficacy and/or safety of iGlarLixi were evaluated.

Identification and Evolutionary Characterization of ARGONAUTE-Binding Platforms.

ARGONAUTE (AGO) proteins are eukaryotic RNA silencing effectors that interact with their binding partners via short peptide motifs known as AGO hooks. AGO hooks tend to cluster in one region of the protein to create an AGO-binding platform. In addition to the presence of AGO hooks, AGO-binding platforms are intrinsically disordered, contain tandem repeat arrays, and have weak sequence conservation even between close relatives.

Lixisenatide, a Once-Daily Prandial Glucagon-Like Peptide-1 Receptor Agonist for the Treatment of Adults with Type 2 Diabetes.

Lixisenatide, a short-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), has been available in Europe since 2013 and was recently approved in the United States for the treatment of type 2 diabetes (T2D) as an adjunct to diet and exercise. The objective of this systematic review is to describe the pharmacology, pharmacokinetics, safety, and efficacy of lixisenatide in patients with T2D. We conducted a search of the EMBASE database, limited to human studies with abstracts available in English.

A Pharmacotherapy Capstone Course to Target Student Learning and Programmatic Curricular Assessment.

To describe how a pharmacotherapy capstone course was used for student learning and programmatic curricular assessment. A pharmacotherapy capstone course was included in the University of Colorado curriculum for 13 years from 2002 through 2014. This 9-credit hour course was the last course prior to Advanced Pharmacy Practice Experiences (APPEs).

Surgical treatment of lung cancer with synchronous adrenal metastases: Adrenalectomy first.

Introduction: The aim of this study is to present our patients with lung cancer and synchronous adrenal metastases treated with a reversal approach: starting with adrenalectomy and doing the lung resection second.

Methods: A total of 108 laparoscopic adrenalectomies were performed, and we analyze a consecutive serie of 10 patients with isolated adrenal synchronous metastases from the lung, surgically treated in a sequential way. All patients underwent staging mediastinoscopy, and patients with positive lymph nodes were primary treated with chemotherapy.

The Impact of a Standalone, Patient-centered Communication Course Series on Student Achievement, Preparedness, and Attitudes.

To evaluate the impact of a standalone, patient-centered communication (PCC) course series on student achievement of and perceived preparedness for PCC skills and to assess student attitudes regarding learning methods used. During curriculum renewal, a standalone PCC course series that integrated horizontally and vertically within the curriculum was developed. Student achievement of outcomes was evaluated by aggregate performance on simulated evaluations.

Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans.

Significant work has been dedicated to the discovery of JAK kinase inhibitors resulting in several compounds entering clinical development and two FDA approved NMEs. However, despite significant effort during the past 2 decades, identification of highly selective JAK3 inhibitors has eluded the scientific community. A significant effort within our research organization has resulted in the identification of the first orally active JAK3 specific inhibitor, which achieves JAK isoform specificity through covalent interaction with a unique JAK3 residue Cys-909.

Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Nonglycemic Outcomes in Patients with Type 2 Diabetes.

The efficacy of the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin in reducing hyperglycemia in patients with type 2 diabetes is well documented. In addition, positive effects have been observed with these agents on nonglycemic variables, such as reductions in body weight and blood pressure, which may confer additional health benefits. SGLT2 inhibitors are also associated with evidence of renal-protecting benefits.

Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies.

Background: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death.

Cardiovascular Outcomes of New Medications for Type 2 Diabetes.

Cardiovascular (CV) disease remains the leading cause of death in people with diabetes, highlighting the importance of using treatment options that do not increase CV risk or possibly decrease CV outcomes. Since 2008, the Food and Drug Administration has required demonstration of CV safety for all new medications developed for the glycemic management of diabetes. Seven trials have been published that have established CV safety for three DPP-4 inhibitors (alogliptin, saxagliptin, and sitagliptin), three GLP-1 receptor agonists (liraglutide, lixisenatide, and semaglutide), and one sodium-glucose cotransporter-2 inhibitor (empagliflozin).

Discovery of a JAK3-Selective Inhibitor: Functional Differentiation of JAK3-Selective Inhibition over pan-JAK or JAK1-Selective Inhibition.

PF-06651600, a newly discovered potent JAK3-selective inhibitor, is highly efficacious at inhibiting γc cytokine signaling, which is dependent on both JAK1 and JAK3. PF-06651600 allowed the comparison of JAK3-selective inhibition to pan-JAK or JAK1-selective inhibition, in relevant immune cells to a level that could not be achieved previously without such potency and selectivity. In vitro, PF-06651600 inhibits Th1 and Th17 cell differentiation and function, and in vivo it reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse experimental autoimmune encephalomyelitis models.

Importance of Urine Dipstick in Evaluation of Young Febrile Infants With Positive Urine Culture: A Spanish Pediatric Emergency Research Group Study.

Background And Objectives: Guidelines from the American Academy of Pediatrics define urinary tract infection (UTI) as the growth of greater than 50,000 ufc/mL of a single bacterium in a urine culture with a positive urine dipstick or with a urinalysis associated. Our objective was to evaluate the adequacy of this cutoff point for the diagnosis of UTI in young febrile infants.

Methods: Subanalysis of a prospective multicenter study developed in RISeuP-SPERG Network between October 11 and September 13.

The effect of obesity on the anatomical relationship of the popliteal artery and tibial nerve in the proximal and distal popliteal fossa: relevance to popliteal sciatic nerve block and a traceback technique using the popliteal artery.

Study Objective: To determine the effect of body mass index (BMI) on the relationship of the popliteal artery to the sciatic and tibial nerves in the popliteal fossa.

Design: Prospective, observational study.

Setting: University medical center.

Detoxification of polycyclic aromatic hydrocarbons (PAHs) in Arabidopsis thaliana involves a putative flavonol synthase.

Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants with cytotoxic, teratogenic and carcinogenic properties. Bioremediation studies with bacteria have led to the identification of dioxygenases (DOXs) in the first step to degrade these recalcitrant compounds. In this study, we characterized the role of the Arabidopsis thaliana AT5G05600, a putative DOX of the flavonol synthase family, in the transformation of PAHs.

Basal Insulin Use With GLP-1 Receptor Agonists.

IN BRIEF The combination of basal insulin and a glucagon-like peptide 1 receptor agonist is becoming increasingly common and offers several potential benefits to patients with type 2 diabetes. Clinical studies have demonstrated improved glycemic control and low risks of hypoglycemia and weight gain with the combination, which provides a safe and effective alternative to basal-bolus insulin with less treatment burden. Fixed-ratio combination products that administer both agents in a single injection are in the pipeline and will offer additional options for clinicians and patients.

Nuclear Magnetic Resonance Measurements and Electronic Structure of Pu(IV) in [(Me)4N]2PuCl6.

The synthesis, electronic structure, and characterization via single-crystal X-ray diffraction, nuclear magnetic resonance (NMR) spectroscopy, and magnetic susceptibility of (Me4N)2PuCl6 are reported. NMR measurements were performed to both search for the direct (239)Pu resonance and to obtain local magnetic and electronic information at the Cl site through (35)Cl and (37)Cl spectra. No signature of (239)Pu NMR was observed.

The Argonaute-binding platform of NRPE1 evolves through modulation of intrinsically disordered repeats.

Argonaute (Ago) proteins are important effectors in RNA silencing pathways, but they must interact with other machinery to trigger silencing. Ago hooks have emerged as a conserved motif responsible for interaction with Ago proteins, but little is known about the sequence surrounding Ago hooks that must restrict or enable interaction with specific Argonautes. Here we investigated the evolutionary dynamics of an Ago-binding platform in NRPE1, the largest subunit of RNA polymerase V.

Association of the FTO (rs9939609) and MC4R (rs17782313) gene polymorphisms with maternal body weight during pregnancy.

Objective: The fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with the risk for obesity, but few studies have examined the association of the obesity risk alleles with gestational outcomes. The aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) of the FTO (rs9939609) and MC4R (rs17782313) genes with changes in maternal body weight during pregnancy.

Methods: A sample of 136 pregnant women were followed in a prospective cohort at 5 to 13, 20 to 26, and 30 to 36 wk gestation and 30 to 45 d postpartum.

Experimental Infection of Calves by Two Genetically-Distinct Strains of Rift Valley Fever Virus.

Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously, we developed a reliable challenge model for sheep that improves the evaluation of existing and novel vaccines in sheep. This sheep model demonstrated differences in the pathogenesis of Rift Valley fever virus (RVFV) infection between two genetically-distinct wild-type strains of the virus, Saudi Arabia 2001 (SA01) and Kenya 2006 (Ken06).

Advances in the treatment of type 2 diabetes: impact of dulaglutide.

The purpose of this review is to provide a review of current data of the most recently approved glucagon-like peptide (GLP)-1-receptor agonist, dulaglutide, in the treatment of type 2 diabetes. To complete this, a PubMed search was performed to identify manuscripts published from 1947 to July 2015. The search terms "Trulicity", "dulaglutide", and "LY2189265" were utilized, and publications were included if they evaluated the pharmacology, pharmacokinetics, efficacy, safety, or patient-reported outcomes of dulaglutide.