Increasing adherence and collecting symptom-specific biometric signals in remote monitoring of heart failure patients: a randomized controlled trial.

Objectives: Mobile health (mHealth) regimens can improve health through the continuous monitoring of biometric parameters paired with appropriate interventions. However, adherence to monitoring tends to decay over time. Our randomized controlled trial sought to determine: (1) if a mobile app with gamification and financial incentives significantly increases adherence to mHealth monitoring in a population of heart failure patients; and (2) if activity data correlate with disease-specific symptoms.

The Projectile Perforation Resistance of Materials: Scaling the Impact Resistance of Thin Films to Macroscale Materials.

From drug delivery to ballistic impact, the ability to control or mitigate the puncture of a fast-moving projectile through a material is critical. While puncture is a common occurrence, which can span many orders of magnitude in the size, speed, and energy of the projectile, there remains a need to connect our understanding of the perforation resistance of materials at the nano- and microscale to the actual behavior at the macroscale that is relevant for engineering applications. In this article, we address this challenge by combining a new dimensional analysis scheme with experimental data from micro- and macroscale impact tests to develop a relationship that connects the size-scale effects and materials properties during high-speed puncture events.

Assessing Boron-Pleuromutilin AN11251 for the Development of Antibacterial Agents.

Pleuromutilins are a group of antibiotics derived from the naturally occurring compound. The recent approval of lefamulin for both intravenous and oral doses in humans to treat community-acquired bacterial pneumonia has prompted investigations in modifying the structure to broaden the antibacterial spectrum, enhance the activity, and improve the pharmacokinetic properties. AN11251 is a C(14)-functionalized pleuromutilin with a boron-containing heterocycle substructure.

A streamlined process for discovery and characterization of inhibitors against phenylalanyl-tRNA synthetase of Mycobacterium tuberculosis.

Aminoacyl-tRNA synthetases (aaRSs) catalyze aminoacylation of tRNAs to produce aminoacyl-tRNAs for protein synthesis. Bacterial aaRSs have distinctive features, play an essential role in channeling amino acids into biomolecular assembly, and are vulnerable to inhibition by small molecules. The aaRSs continue to be targets for potential antibacterial drug development.

Human Kinase IGF1R/IR Inhibitor Linsitinib Controls the In Vitro and Intracellular Growth of .

ATP provides energy in the biosynthesis of cellular metabolites as well as regulates protein functions through phosphorylation. Many ATP-dependent enzymes are antibacterial and anticancer targets including human kinases acted on by most of the successful drugs. In search of new chemotherapeutics for tuberculosis (TB), we screened repurposing compounds against the essential glutamine synthase (GlnA1) of (Mtb) and identified linsitinib, a clinical-stage drug originally targeting kinase IGF1R/IR as a potent GlnA1 inhibitor.

A Computationally Efficient Approach to Simulate Heart Rate Effects Using a Whole Human Heart Model.

Computational modeling of the whole human heart has become a valuable tool to evaluate medical devices such as leadless pacemakers, annuloplasty rings and left ventricular assist devices, since it is often difficult to replicate the complex dynamic interactions between the device and human heart in bench-top and animal tests. The Dassault Systèmes Living Heart Human Model (LHHM) is a finite-element model of whole-human-heart electromechanics that has input parameters that were previously calibrated to generate physiological responses in a healthy heart beating at 60 beat/min (resting state). This study demonstrates that, by adjusting only six physiologically meaningful parameters, the LHHM can be recalibrated to generate physiological responses in a healthy heart beating at heart rates ranging from 90−160 beat/min.

Controlling toughness of polymer-grafted nanoparticle composites for impact mitigation.

Toughness in an entangled polymer network is typically controlled by the number of load-bearing topological constraints per unit volume. In this work, we demonstrate a new paradigm for controlling toughness at high deformation rates in a polymer-grafted nanoparticle composite system where the entanglement density increases with the molecular mass of the graft. An unexpected peak in the toughness is observed right before the system reaches full entanglement that cannot be described through the entanglement concept alone.

Investigate Natural Product Indolmycin and the Synthetically Improved Analogue Toward Antimycobacterial Agents.

Indolmycin (IND) is a microbial natural product that selectively inhibits bacterial tryptophanyl-tRNA synthetase (TrpRS). The tryptophan biosynthesis pathway was recently shown to be an important target for developing new antibacterial agents against (Mtb). We investigated the antibacterial activity of IND against several mycobacterial model strains.

Rediscovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) remains the deadliest pathogenic bacteria worldwide. The search for new antibiotics to treat drug-sensitive as well as drug-resistant tuberculosis has become a priority. The essential enzyme phenylalanyl-tRNA synthetase (PheRS) is an antibacterial drug target because of the large differences between bacterial and human PheRS counterparts.

Re-discovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in .

Mycobacteria tuberculosis (Mtb) remains the deadliest pathogenic bacteria worldwide. The search for new antibiotics to treat drug-sensitive as well as drug-resistant tuberculosis has become a priority. The essential enzyme phenylalanyl-tRNA synthetase (PheRS) is an antibacterial drug target because of the large differences between bacterial and human PheRS counterparts.

Using microprojectiles to study the ballistic limit of polymer thin films.

The dynamic impact between a particle and a planar material is important in many high impact events, and there is a growing need to characterize the mechanical properties of light-weight polymeric materials at dynamic loading conditions. Here, a laser-induced projectile impact test (LIPIT) is employed to investigate the ballistic limit (V0) and materials properties at impact velocities ranging from 40 m s-1 to 70 m s-1. An analytical expression describing the various energy dissipation mechanisms is established to estimate the yield stress and elasticity for polycarbonate thin films.

Estimating the Health-Related Quality of Life of Twitter Users Using Semantic Processing.

Social media presents a rich opportunity to gather health information with limited intervention through the analysis of completely unstructured and unlabeled microposts. We sought to estimate the health-related quality of life (HRQOL) of Twitter users using automated semantic processing methods. We collected tweets from 878 Twitter users recruited through online solicitation and in-person contact with patients.

Total synthesis and antimicrobial evaluation of natural albomycins against clinical pathogens.

Development of effective antimicrobial agents continues to be a great challenge, particularly due to the increasing resistance of superbugs and frequent hospital breakouts. There is an urgent need for more potent and safer antibiotics with novel scaffolds. As historically many commercial drugs were derived from natural products, discovery of antimicrobial agents from complex natural product structures still holds a great promise.

Syncytium calcium signaling and macrophage function in the heart.

Macrophages are traditionally viewed as a key component of the immunity defense system. Recent studies have identified resident macrophages in multiple organs including the heart, in which the cells perform their crucial role on tissue repair after myocardial infarction (MI). The cardiac-specific macrophages interdigitate with cardiomyocytes particularly at the atrioventricular node region.

Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster.

Background: FK506-binding proteins (FKBPs) have become the subject of considerable interest in several fields, leading to the identification of several cellular and molecular pathways in which FKBPs impact prenatal development and pathogenesis of many human diseases.

Main Body: This analysis revealed differences between how mammalian and Drosophila FKBPs mechanisms function in relation to the immunosuppressant drugs, FK506 and rapamycin. Differences that could be used to design insect-specific pesticides.

Nature's combinatorial biosynthesis and recently engineered production of nucleoside antibiotics in Streptomyces.

Modified nucleosides produced by Streptomyces and related actinomycetes are widely used in agriculture and medicine as antibacterial, antifungal, anticancer and antiviral agents. These specialized small-molecule metabolites are biosynthesized by complex enzymatic machineries encoded within gene clusters in the genome. The past decade has witnessed a burst of reports defining the key metabolic processes involved in the biosynthesis of several distinct families of nucleoside antibiotics.

Direct Formation of Oxocarbenium Ions under Weakly Acidic Conditions: Catalytic Enantioselective Oxa-Pictet-Spengler Reactions.

Two catalysts, an amine HCl salt and a bisthiourea, work in concert to enable the generation of oxocarbenium ions under mild conditions. The amine catalyst generates an iminium ion of sufficient electrophilicity to enable 1,2-attack by an alcohol. Catalyst turnover is achieved by amine elimination with concomitant formation of an oxocarbenium intermediate.

Evaluating topic model interpretability from a primary care physician perspective.

Background And Objective: Probabilistic topic models provide an unsupervised method for analyzing unstructured text. These models discover semantically coherent combinations of words (topics) that could be integrated in a clinical automatic summarization system for primary care physicians performing chart review. However, the human interpretability of topics discovered from clinical reports is unknown.

RadPath: A Web-based System for Integrating and Correlating Radiology and Pathology Findings During Cancer Diagnosis.

Rationale And Objectives: The current paradigm of cancer diagnosis involves uncoordinated communication of findings from radiology and pathology to downstream physicians. Discordance between these findings can require additional time from downstream users to resolve, or given incorrect resolution, may adversely impact treatment decisions. To mitigate this problem, we developed a web-based system, called RadPath, for correlating and integrating radiology and pathology reporting.

A Branch Point of Streptomyces Sulfur Amino Acid Metabolism Controls the Production of Albomycin.

Albomycin (ABM), also known as grisein, is a sulfur-containing metabolite produced by Streptomyces griseus ATCC 700974. Genes predicted to be involved in the biosynthesis of ABM and ABM-like molecules are found in the genomes of other actinomycetes. ABM has potent antibacterial activity, and as a result, many attempts have been made to develop ABM into a drug since the last century.

Analysis of the biosynthesis of antibacterial cyclic dipeptides in Nocardiopsis alba.

Nocardiopsis alba is frequently isolated from environment and has recently been suggested as a casual symbiotic actinobacterium of diverse invertebrates. Using activity-guided fractionation, we purified two antibacterial cyclic dipeptides, cyclo(ΔPhe-ΔLeu) (albonoursin) and cyclo(ΔmTyr-ΔLeu), from a culture of Nocardiopsis alba ATCC BAA-2165. Analysis of N.

A replication study for association of ITPKC and CASP3 two-locus analysis in IVIG unresponsiveness and coronary artery lesion in Kawasaki disease.

Single-nucleotide polymorphisms (SNPs) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC, rs28493229) and caspase-3 (CASP3, rs113420705) are associated with susceptibility to KD in Japanese and Taiwanese populations. This study was conducted to investigate the involvement of these 2 SNPs in the risk for intravenous immunoglobulin (IVIG) resistance and coronary artery lesion (CAL) in Taiwanese population. A total of 340 KD patients were subjected to assess by the identification of 2-locus genes model.

Imaging informatics for consumer health: towards a radiology patient portal.

Objective: With the increased routine use of advanced imaging in clinical diagnosis and treatment, it has become imperative to provide patients with a means to view and understand their imaging studies. We illustrate the feasibility of a patient portal that automatically structures and integrates radiology reports with corresponding imaging studies according to several information orientations tailored for the layperson.

Methods: The imaging patient portal is composed of an image processing module for the creation of a timeline that illustrates the progression of disease, a natural language processing module to extract salient concepts from radiology reports (73% accuracy, F1 score of 0.