A Novel Biological Role for Peptidyl-Arginine Deiminases: Citrullination of Cathelicidin LL-37 Controls the Immunostimulatory Potential of Cell-Free DNA.

LL-37, the only human cathelicidin that is released during inflammation, is a potent regulator of immune responses by facilitating delivery of oligonucleotides to intracellular TLR-9, thereby enhancing the response of human plasmacytoid dendritic cells (pDCs) to extracellular DNA. Although important for pathogen recognition, this mechanism may facilitate development of autoimmune diseases. In this article, we show that citrullination of LL-37 by peptidyl-arginine deiminases (PADs) hindered peptide-dependent DNA uptake and sensing by pDCs.

The Coding Regions of Germline mRNAs Confer Sensitivity to Argonaute Regulation in C. elegans.

Protein-coding genes undergo a wide array of regulatory interactions with factors that engage non-coding regions. Open reading frames (ORFs), in contrast, are thought to be constrained by coding function, precluding a major role in gene regulation. Here, we explore Piwi-interacting (pi)RNA-mediated transgene silencing in C.

Impact of an Interprofessional Primary Care Training on Fear of Cancer Recurrence on Clinicians' Knowledge, Self-Efficacy, Anticipated Practice Behaviors, and Attitudes Toward Survivorship Care.

There are an estimated 15.5 million cancer survivors in the United States, with numbers projected to increase. Many cancer survivors are receiving survivorship care in primary care settings, yet primary care providers report a need for additional training on addressing medical and psychosocial concerns of cancer survivors.

Usability and Reliability of Smart Glasses for Secondary Triage During Mass Casualty Incidents.

Wearable smart glasses like Google Glass provide real-time video and image transmission to remote viewers. The use of Google Glass and other Augmented Reality (AR) platforms in mass casualty incidents (MCIs) can provide incident commanders and physicians at receiving hospitals real-time data regarding injuries sustained by victims at the scene. This real-time data is critical to allocation of hospital resources prior to receiving victims of a MCI.

The Development of Benzimidazole-Based Clickable Probes for the Efficient Labeling of Cellular Protein Arginine Deiminases (PADs).

Citrullination is the post-translational hydrolysis of peptidyl-arginines to form peptidyl-citrulline, a reaction that is catalyzed by the protein arginine deiminases (PADs), a family of calcium-regulated enzymes. Aberrantly increased protein citrullination is associated with a slew of autoimmune diseases (e.g.

Total energy expenditure and body composition of children with developmental disabilities.

Background: Obesity prevalence is increased in children with developmental disabilities, specifically in children with spina bifida and Down syndrome. Energy expenditure, a critical aspect of weight management, has been extensively studied in the typically developing population, but not adequately studied in children with developmental disabilities.

Objective: Determine energy expenditure, fat-free mass and body fat percentile and the impact of these findings on recommended caloric intake in children with spina bifida and Down syndrome.

Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.

Long-term epigenetic reprogramming of innate immune cells in response to microbes, also termed "trained immunity," causes prolonged altered cellular functionality to protect from secondary infections. Here, we investigated whether sterile triggers of inflammation induce trained immunity and thereby influence innate immune responses. Western diet (WD) feeding of Ldlr mice induced systemic inflammation, which was undetectable in serum soon after mice were shifted back to a chow diet (CD).

Co-occurrence and Severity of Neurodevelopmental Burden (Cognitive Impairment, Cerebral Palsy, Autism Spectrum Disorder, and Epilepsy) at Age Ten Years in Children Born Extremely Preterm.

Background: This study aims to determine the prevalence of neurodevelopmental impairments at age ten years among children born extremely preterm (less than 28 weeks gestational age) and to offer a framework for categorizing neurological limitations.

Methods: A multicenter, prospective cohort follow-up study recruited 889 ten-year-old children born from 2002 to 2004. We assessed prevalence of cognitive impairment, measured by intelligent quotient and tests of executive function, cerebral palsy (CP), autism spectrum disorder (ASD), and epilepsy singly and in combination.

The diagnostic value of FNA biopsy in grading pancreatic neuroendocrine tumors.

Background: There has been much controversy regarding the accuracy of grading pancreatic neuroendocrine tumors (PNETs) on fine-needle aspiration (FNA) biopsy. The objectives of this study were to evaluate whether grading according to the fraction of Ki-67-positive tumor cells (the Ki-67 proliferation index) on material from endoscopic ultrasound-guided FNA biopsies correlated with grading on surgical resection specimens and to evaluate the minimum amount of FNA material needed.

Methods: A case series of 27 PNETs with FNA biopsies and corresponding surgical resection specimens at the authors' institution were evaluated.

Single incision laparoscopic proficiency correlates with residency training level.

Background: With experience, certain psychomotor skills should translate from standard laparoscopy to single-incision laparoscopy (SIL). We proposed to compare all surgical postgraduate year (PGY) levels and determine if experience translated to improved SIL skills.

Methods: Surgical residents of all PGY levels (1-5) at our institution were included.

Vector velocity imaging echocardiography to study the effects of submassive pulmonary embolism on the right atrium.

Objectives: To assess the effects of submassive pulmonary embolism (SMPE) on right atrial (RA) anatomy and function.

Background: Right ventricular dysfunction (RVD) is associated with adverse outcomes in SMPE. However, the effects of SMPE on the structure and function of the RA have received much less attention.

Sensory Sensitivity and Food Selectivity in Children with Autism Spectrum Disorder.

Few studies have compared atypical sensory characteristics and food selectivity between children with and without autism spectrum disorder (ASD). We compared oral sensory processing between children with (n = 53) and without ASD (n = 58), ages 3-11 years. We also examined the relationships between atypical oral sensory processing, food selectivity, and fruit/vegetable consumption in children with ASD.

IsomiR processing during differentiation of myelogenous leukemic cell line K562 by phorbol ester PMA.

Chronic myelocytic leukemia cell line K562 undergoes differentiation by phorbol esters to megakaryocytes and we have used this system to understand miRNA processing leading to isomiR generation. PMA treatment significantly altered the production of miRNA in K562 cells. Expression of 24.

Predictors of Persistent Infant Car Seat Challenge Failure.

Background: Premature and other at-risk infants can experience cardiorespiratory problems when positioned in their car seats. The American Academy of Pediatrics recommends that all premature and at-risk infants undergo a period of observation in their car seat to monitor for apnea, bradycardia, and oxygen desaturation before hospital discharge. This Infant Car Seat Challenge (ICSC) is used to determine readiness for infant travel in a car seat.

Locked Nucleic Acid Gapmers and Conjugates Potently Silence ADAM33, an Asthma-Associated Metalloprotease with Nuclear-Localized mRNA.

Two mechanisms dominate the clinical pipeline for oligonucleotide-based gene silencing, namely, the antisense approach that recruits RNase H to cleave target RNA and the RNAi approach that recruits the RISC complex to cleave target RNA. Multiple chemical designs can be used to elicit each pathway. We compare the silencing of the asthma susceptibility gene ADAM33 in MRC-5 lung fibroblasts using four classes of gene silencing agents, two that use each mechanism: traditional duplex small interfering RNAs (siRNAs), single-stranded small interfering RNAs (ss-siRNAs), locked nucleic acid (LNA) gapmer antisense oligonucleotides (ASOs), and novel hexadecyloxypropyl conjugates of the ASOs.

Dapagliflozin/Saxagliptin Fixed-Dose Tablets: A New Sodium-Glucose Cotransporter 2 and Dipeptidyl Peptidase 4 Combination for the Treatment of Type 2 Diabetes.

Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of the fixed-dose combination (FDC) product, QTERN (dapagliflozin/saxagliptin) tablets.

Data Sources: Searches of MEDLINE (1946 to July 1, 2017) were conducted using the keywords QTERN, saxagliptin, and dapagliflozin. Additional data were obtained from the prescribing information, the product dossier, and Clinicaltrials.

"Forgotten" Chapters in the History of Transcervical Sterilization: Carl Clauberg and Hans-Joachim Lindemann.

Transcervical sterilization is a non-surgical method of permanent female sterilization that is widely used and critically discussed. A review of the historiography of the method reveals that instances of its coercive use are not included in the historical account. This study offers a reexamination of the work of Carl Clauberg and Hans-Joachim Lindemann, to more deeply contextualize within the framework of current usage the coercive use of transcervical sterilization during the Third Reich and in postwar Germany.

Long-Term Effectiveness of Adalimumab in Patients with Rheumatoid Arthritis: An Observational Analysis from the Corrona Rheumatoid Arthritis Registry.

Introduction: Current recommendations for the management of rheumatoid arthritis (RA) focus on a treat-to-target approach with the objective of maximizing long-term health-related quality-of-life in patients with RA. Published studies from randomized clinical trials have reported limited data regarding the long-term efficacy and safety of adalimumab in patients with RA. This study aims to evaluate the long-term (10+ years) persistency and effectiveness of adalimumab in patients with RA in a real-world setting.

Gelsolin dysfunction causes photoreceptor loss in induced pluripotent cell and animal retinitis pigmentosa models.

Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause X-linked RP (XLRP), an untreatable, inherited retinal dystrophy that leads to premature blindness. RPGR localises to the photoreceptor connecting cilium where its function remains unknown. Here we show, using murine and human induced pluripotent stem cell models, that RPGR interacts with and activates the actin-severing protein gelsolin, and that gelsolin regulates actin disassembly in the connecting cilium, thus facilitating rhodopsin transport to photoreceptor outer segments.

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline.

Gene Therapy Using a miniCEP290 Fragment Delays Photoreceptor Degeneration in a Mouse Model of Leber Congenital Amaurosis.

Mutations in the cilia-centrosomal protein CEP290 are frequently observed in autosomal recessive childhood blindness disorder Leber congenital amaurosis (LCA). No treatment or cure currently exists for this disorder. The Cep290 (retinal degeneration 16) mouse (a model of LCA) carries a mutation in the Cep290 gene.