Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells.

The cAMP-dependent aquaporin-2 (AQP2) redistribution from intracellular vesicles into the plasma membrane of renal collecting duct principal cells induces water reabsorption and fine-tunes body water homeostasis. However, the mechanisms controlling the localization of AQP2 are not understood in detail. Using immortalized mouse medullary collecting duct (MCD4) and primary rat inner medullary collecting duct (IMCD) cells as model systems, we here discovered a key regulatory role of Aurora kinase A (AURKA) in the control of AQP2.

Improvement of the antimicrobial potency, pharmacokinetic and pharmacodynamic properties of albicidin by incorporation of nitrogen atoms.

The worrisome development and spread of multidrug-resistant bacteria demands new antibacterial agents with strong bioactivities particularly against Gram-negative bacteria. Albicidins were recently structurally characterized as highly active antibacterial natural products from the bacterium . Albicidin, which effectively targets the bacterial DNA-gyrase, is a lipophilic hexapeptide mostly consisting of amino benzoic acid units and only one α-amino acid.

Overcoming AlbD Protease Resistance and Improving Potency: Synthesis and Bioactivity of Antibacterial Albicidin Analogues with Amide Bond Isosteres.

Albicidin is a potent antibacterial oligoaromatic peptide that is susceptible to the protease AlbD, a resistance factor. This potentially restricts the use of albicidin as a drug. To overcome this obstacle, we synthesized and evaluated six analogues with isosteric replacement of the key amide link.

Acetylenic Replacement of Albicidin's Methacrylamide Residue Circumvents Detrimental E/Z Photoisomerization and Preserves Antibacterial Activity.

The natural product albicidin is a highly potent inhibitor of bacterial DNA gyrase. Its outstanding activity, particularly against Gram-negative pathogens, qualifies it as a promising lead structure in the search for new antibacterial drugs. However, as we show here, the N-terminal cinnamoyl moiety of albicidin is susceptible to photochemical E/Z isomerization.

SAR340835, a Novel Selective Na/Ca Exchanger Inhibitor, Improves Cardiac Function and Restores Sympathovagal Balance in Heart Failure.

In failing hearts, Na/Ca exchanger (NCX) overactivity contributes to Ca depletion, leading to contractile dysfunction. Inhibition of NCX is expected to normalize Ca mishandling, to limit afterdepolarization-related arrhythmias, and to improve cardiac function in heart failure (HF). SAR340835/SAR296968 is a selective NCX inhibitor for all NCX isoforms across species, including human, with no effect on the native voltage-dependent calcium and sodium currents in vitro.

Extensive Structure-Activity Relationship Study of Albicidin's C-Terminal Dipeptidic p-Aminobenzoic Acid Moiety.

Albicidin is a recently described natural product that strongly inhibits bacterial DNA gyrase. The pronounced activity, particularly against Gram-negative bacteria, turns it into a promising lead structure for an antibacterial drug. Hence, structure-activity relationship studies are key for the in-depth understanding of structural features/moieties affecting gyrase inhibition, antibacterial activity and overcoming resistance.

Medium-Term Outcomes With Pyrocarbon Proximal Interphalangeal Arthroplasty: A Study of 170 Consecutive Arthroplasties.

Purpose: The purpose of this study was to examine the medium-term outcomes of patients undergoing proximal interphalangeal (PIP) joint arthroplasty using a pyrocarbon implant.

Methods: The study comprised an analysis of 170 PIP joint pyrocarbon arthroplasties in 99 patients with a minimum 2-year clinical follow-up. Diagnoses included inflammatory arthritis (n = 49), posttraumatic arthritis (n = 29), and osteoarthritis (n = 92).

Total Synthesis and Biological Assessment of Novel Albicidins Discovered by Mass Spectrometric Networking.

Natural products represent an important source of potential novel antimicrobial drug leads. Low production by microorganisms in cell culture often delays the structural elucidation or even prevents a timely discovery. Starting from the anti-Gram-negative antibacterial compound albicidin produced by Xanthomonas albilineans, we describe a bioactivity-guided approach combined with non-targeted tandem mass spectrometry and spectral (molecular) networking for the discovery of novel antimicrobial compounds.

Discovery and Optimization of 1-Phenoxy-2-aminoindanes as Potent, Selective, and Orally Bioavailable Inhibitors of the Na/H Exchanger Type 3 (NHE3).

The design, synthesis, and structure-activity relationship of 1-phenoxy-2-aminoindanes as inhibitors of the Na/H exchanger type 3 (NHE3) are described based on a hit from high-throughput screening (HTS). The chemical optimization resulted in the discovery of potent, selective, and orally bioavailable NHE3 inhibitors with 13d as best compound, showing high in vitro permeability and lacking CYP2D6 inhibition as main optimization parameters. Aligning 1-phenoxy-2-aminoindanes onto the X-ray structure of 13d then provided 3D-QSAR models for NHE3 inhibition capturing guidelines for optimization.

Synthesis of Albicidin Derivatives: Assessing the Role of N-terminal Acylation on the Antibacterial Activity.

The peptide antibiotic albicidin, which is synthesized by the plant pathogenic bacterium, Xanthomonas albilineans, represents the most prominent member of a new class of antibacterial gyrase inhibitors. It shows remarkable antibacterial activities against Gram-positive and Gram-negative microorganisms. Its unique structure potentially represents a new lead structure for the development of an antibacterial drug.

Closing the Gap Between Esthetics and Digital Dentistry.

While digital methods have a firm position in dentistry, a total digital workflow for multi-unit layered restorations has yet to be fully realized. Many clinicians are using a CAD/CAM workflow of some kind, but there is still a significant gap to be filled for completing the digital workflow. This article describes how practitioners can transition into the full digital workflow, showing the use of digital processes for anterior cosmetic cases.

Synthesis and Antimicrobial Activity of Albicidin Derivatives with Variations of the Central Cyanoalanine Building Block.

To investigate the pharmacophore regions of the antibiotic albicidin, derivatives with variations on the central amino acid were synthesized. Charged as well as uncharged residues were chosen to explore the influence of charge, chirality, and steric bulk. The bioactivity of the newly synthesized derivatives was determined by a microdilution technique to obtain minimum inhibitory concentrations (MIC) values.

A systematic review of total dislocation of the talus.

This review summarizes the treatment and resulting outcomes for total talar dislocation. The PubMed database was searched for articles about humans with total talar dislocation published in the English language in the last twenty years. The following data were entered into a Microsoft Excel spreadsheet: type of dislocation, nature of associated fractures (if any), type of reduction/fixation utilized, immobilization, weight-bearing status, outcome, complications and average follow-up time.

Use of a resin-modified glass-ionomer (RMGI) liner in conservative direct treatment of deep caries.

Liners and bases are a class of dental materials that provide added protection for the health and well-being of a tooth being restored. They help prevent postoperative sensitivity resulting from an incomplete dentinal seal. Some practitioners use them, while others choose not to.

The association between medial malleolar fracture geometry, injury mechanism, and syndesmotic disruption.

Background: Precise correlations between medial malleolar fracture geometry and fracture mechanism have not been thoroughly described. This study sought to determine the prevalence of different medial malleolar fracture types and to elucidate the association between fracture geometry and fracture mechanism.

Methods: The records of 112 medial malleolar ankle fractures were reviewed.

Predictable nanohybrid composite systems and techniques for anterior and posterior direct restorations.

Advancements in the chemical composition of direct restorative materials have facilitated greater ease of use, better handling, and enhanced functional predictability. Nanohybrid composites are among these innovations, providing enhanced physical and optical properties that contribute to easier and long-lasting polishability, enhanced shade matching and light reflection/deflection properties, and reduced shrinkage. Becoming familiar with a particular composite system and following a repeatable protocol for routine restorations are key to achieving predictable and long-lasting restorative results.

Comparison of surgical techniques of 111 medial malleolar fractures classified by fracture geometry.

Background: Evaluation of operative techniques used for medial malleolar fractures by classifying fracture geometry has not been well documented.

Methods: One hundred eleven patients with medial malleolar fractures (transverse n = 63, oblique n = 29, vertical n = 7, comminuted n = 12) were included in this study. Seventy-two patients had complicating comorbidities.

Isolated subtalar dislocation.

EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Understand the etiology, epidemiology, and importance of treatment of isolated subtalar dislocation. 2.

Nociceptin Signaling Involves a Calcium-Based Depolarization in Tetrahymena thermophila.

Tetrahymena thermophila are free-living, ciliated eukaryotes. Their behavioral response to stimuli is well characterized and easily observable, since cells swim toward chemoattractants and avoid chemorepellents. Chemoattractant responses involve increased swim speed or a decreased change in swim direction, while chemorepellent signaling involves ciliary reversal, which causes the organism to jerk back and forth, swim in small circles, or spin in an attempt to get away from the repellent.

Characteristics of hospital observation services: a society of cardiovascular patient care survey.

Introduction: Little is known about the setting in which observation services are provided, or how observation patients are managed in settings such as accredited cardiovascular patient care centers.

Objective: To describe the characteristics of observation services in accredited Cardiovascular Patient Care hospitals, or those seeking accreditation.

Methods: This is a cross-sectional survey of hospitals either accredited by the Society of Cardiovascular Patient Care, or considering accreditation in 2010.

Conservative full-mouth reconstruction of a worn dentition utilizing digital impression technology and modern ceramic materials.

Good communication and advanced planning were two keys used in this case to provide the patient with a predictable, clinically acceptable outcome of improved esthetics while preserving tooth structure. Demonstrating the successful integration of various dental specialists, the case utilized new technology that included chairside optical scanning and stereolithic modeling. The goals of improving the patient's smile and function were achieved.

In-practice evaluation of OraVerse for the reversal of soft-tissue anesthesia after dental procedures.

This study investigated the pattern of use, dentist evaluation, and patient assessment of OraVerse (OV), a solution of phentolamine mesylate formulated for intraoral submucosal injection and used for the reversal of soft anesthesia after dental procedures. Participants were provided the drug for treatment of up to 10 patients each and agreed to complete a 26-item evaluation questionnaire at the end of the clinical assessment. Data were available from 51 dentists reporting on 390 patients 4 to 90 years of age.

Creating aesthetic success through proper clinician and laboratory technical communication.

High-quality aesthetic restorations that look great, function ideally, and last can only be predictably produced through implementation of excellent communication techniques and systems between the doctor and ceramist. With the availability of technology and the Internet, it is now easy to involve the laboratory via digital photographs. This article challenges one to begin including the laboratory early in the process and routinely use reliable techniques to transfer clinically significant information to the laboratory bench.