Design and Characterization of Compact, Programmable, Multistranded Nonimmunostimulatory Nucleic Acid Nanoparticles Suitable for Biomedical Applications.

We report a thorough investigation of the role of single-stranded thymidine (ssT) linkers in the stability and flexibility of minimal, multistranded DNA nanostructures. We systematically explore the impact of varying the number of ssTs in three-way junction motifs (3WJs) on their formation and properties. Through various UV melting experiments and molecular dynamics simulations, we demonstrate that while the number of ssTs minimally affects thermodynamic stability, the increasing ssT regions significantly enhance the structural flexibility of 3WJs.

A CAF-Fueled TIMP-1/CD63/ITGB1/STAT3 Feedback Loop Promotes Migration and Growth of Breast Cancer Cells.

TIMP-1 is one of the many factors that CAFs have been shown to secret. TIMP-1 can act in a tumor-supportive or tumor-suppressive manner. The purpose of this study was to elucidate the role of CAF-secreted TIMP-1 for the effects of CAFs on breast cancer cell behavior.

Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer.

Broxbam, also known as N-hydroxy-4-{1-methoxy-4-[4'-(3'-bromo-4',5'-dimethoxyphenyl)-oxazol-5'-yl]-2-phenoxy} butanamide, is a novel chimeric inhibitor that contains two distinct pharmacophores in its molecular structure. It has been previously demonstrated to inhibit the activity of histone deacetylases (HDAC) and tubulin polymerisation, two critical components required for cancer growth and survival. In the present study, the potential suitability of broxbam for the treatment of liver cancer was investigated.

On the Role of Hydrogen Bonding in Gas-Phase S2 Reactions at Silicon.

The shape of the potential energy surface (PES) of gas-phase S2 reactions at silicon is determined by the type of nucleophile, the leaving group, and substituents which remain bonded to silicon. In this study, we present PES scans along the reaction coordinate of six symmetrical S2 reactions: X + SiRX → XSiR + X, where X = Cl or F and R = H, Me, or OMe. While the fluorine systems and the ClSiHCl system only give single-well PESs, ClSiMeCl and ClSi(OMe)Cl give triple- and double-well PESs with stable pre- and post-reaction complexes.

Immediate Effects of Limb Rotational Kinesio Tape Application on Upper Quarter Y-Balance Test Scores.

Context: Rounded shoulder posture is a common problem in the athletic population. Recently Kinesio tape has been utilized to improve balance, proprioception, and posture. However, the literature has been unable to provide definitive answers on the efficacy of Kinesio tape use.

Carcinoma-Associated Fibroblasts Promote Growth of Sox2-Expressing Breast Cancer Cells.

CAFs (Carcinoma-associated fibroblasts) play an important role in cancer progression. For instance, they promote resistance to anti-estrogens, such as fulvestrant. Here, we show that, in ERα-positive breast cancer cell lines, the cocktail of factors secreted by CAFs (CAF-CM) induce the expression of the embryonal stem cell transcription factor Sox2 (sex determining region Y (SRY)-box 2).

Computation of NMR Shielding Constants for Solids Using an Embedded Cluster Approach with DFT, Double-Hybrid DFT, and MP2.

In this work, we explore the accuracy of post-Hartree-Fock (HF) methods and double-hybrid density functional theory (DFT) for the computation of solid-state NMR chemical shifts. We apply an embedded cluster approach and investigate the convergence with cluster size and embedding for a series of inorganic solids with long-range electrostatic interactions. In a systematic study, we discuss the cluster design, the embedding procedure, and basis set convergence using gauge-including atomic orbital (GIAO) NMR calculations at the DFT and MP2 levels of theory.

Sila-Ibuprofen.

The synthesis, characterization, biological activity, and toxicology of sila-ibuprofen, a silicon derivative of the most common nonsteroidal anti-inflammatory drug, is reported. The key improvements compared with ibuprofen are a four times higher solubility in physiological media and a lower melting enthalpy, which are attributed to the carbon-silicon switch. The improved solubility is of interest for postsurgical intravenous administration.

Pulling the Trigger: Recommendations for Surgical Care of the Pediatric Trigger Thumb.

Background: Despite being a common pediatric hand condition, there are few clear guidelines regarding the optimal management of pediatric trigger thumb. Our primary aim was to help guide surgical management of this disorder by establishing a treatment algorithm on the basis of our institution's experience.

Methods: This is an institutional review board-approved retrospective study of all patients with idiopathic trigger thumbs from 2005 to 2015 at a single institution.

Evaluation of student perceptions of introductory pharmacy practice experiences.

Introduction: Introductory pharmacy practice experiences (IPPEs) are focused on sharpening the student's knowledge, skills, abilities, and attitudes related to becoming an effective member of the healthcare team. Currently, the literature on student pharmacists' perceptions focused only on advanced pharmacy practice experiences (APPEs). This study gathered perceptions of IPPEs from pharmacy students in their first through third year professional years.

Effects of pharmacy interventions at transitions of care on patient outcomes.

Purpose: An interdisciplinary group developed a care transitions process with a prominent pharmacist role.

Methods: The new transitions process was initiated on a 32-bed medical/surgical unit. Demographics, reconciliation data, information on medication adherence barriers, medication recommendations, and time spent performing interventions were prospectively collected for 284 consecutive patients over 54 days after the pharmacy participation was completely implemented.

Protein‑ and growth‑modulatory effects of carcinoma‑associated fibroblasts on breast cancer cells: Role of interleukin‑6.

Carcinoma‑associated fibroblasts (CAFs) secrete factors that increase the expression and/or activities of proteins in breast cancer cells and induce resistance to anti‑estrogens, such as fulvestrant. A major factor is interleukin‑6 (IL‑6). This study demonstrated that, across estrogen receptor (ER)α‑positive and ‑negative cell lines, recombinant human IL‑6 (rhIL‑6) mimicked most of the CAF‑conditioned medium (CM)‑induced changes in protein expression patterns; however, in most cases, it failed to recapitulate CAF‑CM‑triggered alterations in ERK1/2 and AKT activities.

Antitumor and antiangiogenic activity of the novel chimeric inhibitor animacroxam in testicular germ cell cancer.

Chimeric inhibitors, which merge two drug pharmacophores in a single molecule have become a prominent approach for the design of novel anticancer compounds. Here, we examined animacroxam, which combines histone deacetylase (HDAC) inhibitory and cytoskeleton-interfering pharmacophores, in testicular germ cell tumors (TGCT). The effectiveness of animacroxam was compared to that of the commonly applied chemotherapeutic cisplatin as well as the clinically approved HDAC inhibitor vorinostat.

Accurate Band Gap Predictions of Semiconductors in the Framework of the Similarity Transformed Equation of Motion Coupled Cluster Theory.

In this work, we present a detailed comparison between wave-function-based and particle/hole techniques for the prediction of band gap energies of semiconductors. We focus on the comparison of the back-transformed Pair Natural Orbital Similarity Transformed Equation of Motion Coupled-Cluster (bt-PNO-STEOM-CCSD) method with Time Dependent Density Functional Theory (TD-DFT) and Delta Self Consistent Field/DFT (Δ-SCF/DFT) that are employed to calculate the band gap energies in a test set of organic and inorganic semiconductors. Throughout, we have used cluster models for the calculations that were calibrated by comparing the results of the cluster calculations to periodic DFT calculations with the same functional.

Pediatric Forearm Fractures Are Effectively Immobilized With a Sugar-Tong Splint Following Closed Reduction.

Introduction: Following closed reduction and initial casting of pediatric forearm fractures, loss of reduction (LOR) occurs in ∼5% to 75% of fractures. Sugar-tong splinting has been shown to maintain acceptable reduction in pediatric distal radius fractures while potentially avoiding issues associated with circumferential casting. We hypothesized that the sugar-tong splint would be an acceptable method for initial immobilization to prevent LOR in distal, mid-shaft, and proximal pediatric forearm fractures.

Oxazole-Bridged Combretastatin A-4 Derivatives with Tethered Hydroxamic Acids: Structure⁻Activity Relations of New Inhibitors of HDAC and/or Tubulin Function.

New inhibitors of tubulin polymerization and/or histone deacetylase (HDAC) activity were synthesized by attaching alkyl tethered hydroxamic acid appendages of varying length to oxazole-bridged combretastatin A-4 analogous caps. While their antiproliferative and microtubule disrupting effect was most pronounced for derivatives with short spacers, HDAC inhibition was strongest for those with longer spacers. These findings were further supported by computational methods such as structure-based docking experiments exploring the target interactions of the derivatives with varying linkers.

Long-term exposure to carcinoma-associated fibroblasts makes breast cancer cells addictive to integrin β1.

We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells.

Human Decisions in Moral Dilemmas are Largely Described by Utilitarianism: Virtual Car Driving Study Provides Guidelines for Autonomous Driving Vehicles.

Ethical thought experiments such as the trolley dilemma have been investigated extensively in the past, showing that humans act in utilitarian ways, trying to cause as little overall damage as possible. These trolley dilemmas have gained renewed attention over the past few years, especially due to the necessity of implementing moral decisions in autonomous driving vehicles (ADVs). We conducted a set of experiments in which participants experienced modified trolley dilemmas as drivers in virtual reality environments.

Animacroxam, a Novel Dual-Mode Compound Targeting Histone Deacetylases and Cytoskeletal Integrity of Testicular Germ Cell Cancer Cells.

Novel approaches for the medical treatment of advanced solid tumors, including testicular germ cell tumors (TGCT), are desperately needed. Especially, TGCT patients not responding to cisplatin-based therapy need therapeutic alternatives, as there is no effective medical treatment available for this particular subgroup. Here, we studied the suitability of the novel dual-mode compound animacroxam for TGCT treatment.

Tetrahalogenated benzimidazole D-ribonucleosides are active against rat cytomegalovirus.

Background: Benzimidazole D-ribonucleosides are potent and selective inhibitors of CMV infection that have been shown to target the viral terminase, the enzyme complex responsible for viral DNA cleavage into single unit-length genomes and subsequent DNA packaging into procapsids. Here, we evaluated the viral inhibition by benzimidazole D-ribonucleosides against rat cytomegalovirus (RCMV).

Methods: Antiviral activity of compounds ClRB and BTCRB against RCMV was quantified by measurement of plaque formation.

Expression of transmembrane protein 26 (TMEM26) in breast cancer and its association with drug response.

We have previously shown that stromal cells desensitize breast cancer cells to the anti-estrogen fulvestrant and, along with it, downregulate the expression of TMEM26 (transmembrane protein 26). In an effort to study the function and regulation of TMEM26 in breast cancer cells, we found that breast cancer cells express non-glycosylated and N-glycosylated isoforms of the TMEM26 protein and demonstrate that N-glycosylation is important for its retention at the plasma membrane. Fulvestrant induced significant changes in expression and in the N-glycosylation status of TMEM26.

Intracellular Distribution of Capsid-Associated pUL77 of Human Cytomegalovirus and Interactions with Packaging Proteins and pUL93.

Unlabelled: DNA packaging into procapsids is a common multistep process during viral maturation in herpesviruses. In human cytomegalovirus (HCMV), the proteins involved in this process are terminase subunits pUL56 and pUL89, which are responsible for site-specific cleavage and insertion of the DNA into the procapsid via portal protein pUL104. However, additional viral proteins are required for the DNA packaging process.

Stromal cells promote anti-estrogen resistance of breast cancer cells through an insulin-like growth factor binding protein 5 (IGFBP5)/B-cell leukemia/lymphoma 3 (Bcl-3) axis.

There is strong evidence that stromal cells promote drug resistance of cancer. Here, we show that mesenchymal stem cells (MSCs) and carcinoma-associated fibroblasts (CAFs) desensitize ERα-positive breast cancer cells to the anti-estrogen fulvestrant. In search for the mechanism, we found that MSCs and CAFs similarly increased the activity of the PI3K/AKT and the JAK/STAT3 pathways and upregulated the expression of integrin β1, IGF1R, HIF1α, CAIX and Bcl-3 in MCF-7 cells.

Cable Bacteria in Freshwater Sediments.

In marine sediments cathodic oxygen reduction at the sediment surface can be coupled to anodic sulfide oxidation in deeper anoxic layers through electrical currents mediated by filamentous, multicellular bacteria of the Desulfobulbaceae family, the so-called cable bacteria. Until now, cable bacteria have only been reported from marine environments. In this study, we demonstrate that cable bacteria also occur in freshwater sediments.