Cranial Dislocation of Infrarenal Aortic Endoprostheses During Transcatheter Aortic Valve Replacement.

This report describes the complexity of transcatheter aortic valve replacement in which rare complications sometimes occur, even at experienced centers. This is a case of cranial migration of an infrarenal aortic aneurysm endograft while advancing the balloon-expandable prosthesis through the infrarenal aorta, which was subsequently successfully treated by deploying a thoracic endoprosthesis after deployment of the aortic valve bioprosthesis.

DNAzyme Cleavage of CAG Repeat RNA in Polyglutamine Diseases.

CAG repeat expansion is the genetic cause of nine incurable polyglutamine (polyQ) diseases with neurodegenerative features. Silencing repeat RNA holds great therapeutic value. Here, we developed a repeat-based RNA-cleaving DNAzyme that catalyzes the destruction of expanded CAG repeat RNA of six polyQ diseases with high potency.

System of Psychological Support Based on Positive Suggestions to the Critically Ill Using ICU Doulas.

Unlabelled: Surviving critical illness often creates a lasting psychological impact, including depression, anxiety, and post-traumatic stress. Memories of frightening and delusional experiences are the largest potentially modifiable risk factor, but currently, there is no proven intervention to improve these inciting factors. Psychological support based on positive suggestion is a psychotherapeutic approach that can be provided even to patients in altered cognitive states and is therefore a viable psychotherapy intervention throughout the ICU stay.

Improved Oxidative C-C Bond Formation Reactivity of High-Valent Pd Complexes Supported by a Pseudo-Tridentate Ligand.

There is a large interest in developing oxidative transformations catalyzed by palladium complexes that employ environmentally friendly and economical oxidizing reagents such as dioxygen. Recently, we have reported the isolation and characterization of various mononuclear Pd and Pd complexes supported by the tetradentate ligands ,'-dialkyl-2,11-diaza[3.3](2,6)pyridinophane (N4, R = Bu, Pr, Me), and the aerobically induced C-C and C-heteroatom bond formation reactivity was investigated in detail.

Improved synthesis of symmetrically & asymmetrically N-substituted pyridinophane derivatives.

The N,N'-di(toluenesulfonyl)-2,11-diaza[3,3](2,6)pyridinophane (N4) precursor was sought after as a starting point for the preparation of various symmetric and asymmetric pyridinophane-derived ligands. Various procedures to synthesize N4 had been published, but the crucial problem had been the purification of N4 from the larger 18- and 24-membered azamacrocycles. Most commonly, column chromatography or other laborious methods have been utilized for this separation, yet we have found an alternate selective dissolution method upon protonation which allows for multi-gram scale output of N4·HCl.

Coordination Chemistry of Bifunctional Chemical Agents Designed for Applications in Cu PET Imaging for Alzheimer's Disease.

Positron emission tomography (PET) is emerging as one of the most important diagnostic tools for brain imaging, yet the most commonly used radioisotopes in PET imaging, C and F, have short half-lives, and their usage is thus somewhat limited. By comparison, the Cu radionuclide has a half-life of 12.7 h, which is ideal for administering and imaging purposes.

Evaluation of Cu-Based Radiopharmaceuticals that Target Aβ Peptide Aggregates as Diagnostic Tools for Alzheimer's Disease.

Positron emission tomography (PET) imaging agents that detect amyloid plaques containing amyloid beta (Aβ) peptide aggregates in the brain of Alzheimer's disease (AD) patients have been successfully developed and recently approved by the FDA for clinical use. However, the short half-lives of the currently used radionuclides C (20.4 min) and F (109.

Facile Preparation of Stable Antibody-Gold Conjugates and Application to Affinity-Capture Self-Interaction Nanoparticle Spectroscopy.

Protein-nanoparticle conjugates are widely used for conventional applications such as immunohistochemistry and biomolecular detection as well as emerging applications such as therapeutics and advanced materials. Nevertheless, it remains challenging to reproducibly prepare stable protein-nanoparticle conjugates with highly similar optical properties. Here we report an improved physisorption method for reproducibly preparing stable antibody-gold conjugates at acidic pH using polyclonal antibodies from a wide range of species (human, goat, rabbit, mouse, and rat).

Isolated Organometallic Nickel(III) and Nickel(IV) Complexes Relevant to Carbon-Carbon Bond Formation Reactions.

Nickel-catalyzed cross-coupling reactions are experiencing a dramatic resurgence in recent years given their ability to employ a wider range of electrophiles as well as promote stereospecific or stereoselective transformations. In contrast to the extensively studied Pd catalysts that generally employ diamagnetic intermediates, Ni systems can more easily access various oxidation states including odd-electron configurations. For example, organometallic Ni intermediates with aryl and/or alkyl ligands are commonly proposed as the active intermediates in cross-coupling reactions.

Evidence for a cysteine-mediated mechanism of excitation energy regulation in a photosynthetic antenna complex.

Light-harvesting antenna complexes not only aid in the capture of solar energy for photosynthesis, but regulate the quantity of transferred energy as well. Light-harvesting regulation is important for protecting reaction center complexes from overexcitation, generation of reactive oxygen species, and metabolic overload. Usually, this regulation is controlled by the association of light-harvesting antennas with accessory quenchers such as carotenoids.

Perturbation of the O-U-O Angle in Uranyl by Coordination to a 12-Membered Macrocycle.

Reaction of [UO2Cl2(THF)2]2 (THF = tetrahydrofuran) with 2 equiv of (H)N4 ((H)N4 = 2,11-diaza[3,3](2,6) pyridinophane) or (Me)N4 ((Me)N4 = N,N'-dimethyl-2,11-diaza[3,3](2,6) pyridinophane), in MeCN, results in the formation of UO2Cl2((R)N4) (R = H; 1; Me, 2), which were isolated as yellow-orange solids in good yields. Similarly, reaction of UO2(OTf)2(THF)3 with (H)N4 in MeCN results in the formation of UO2(OTf)2((H)N4) (3), as an orange powder in 76% yield. Finally, reaction of UO2(OTf)2(THF)3 with (Me)N4 in THF results in the formation of [UO2(OTf)(THF)((H)N4)][OTf] (4), as an orange powder in 73% yield.

Aromatic Cyanoalkylation through Double C-H Activation Mediated by Ni(III).

Herein we report an atom- and step-economic aromatic cyanoalkylation reaction that employs nitriles as building blocks and proceeds through Csp(2)-H and Csp(3)-H bond activation steps mediated by Ni(III). In addition to cyanomethylation with MeCN, regioselective α-cyanoalkylation was observed with various nitrile substrates to generate secondary and tertiary nitriles. Importantly, to the best of our knowledge these are the first examples of C-H bond activation reactions occurring at a Ni(III) center, which may exhibit different reactivity and selectivity profiles than those corresponding to analogous Ni(II) centers.

Discovery of highly soluble antibodies prior to purification using affinity-capture self-interaction nanoparticle spectroscopy.

Self-association of monoclonal antibodies (mAbs) at high concentrations can result in developability challenges such as poor solubility, aggregation, opalescence and high viscosity. There is a significant unmet need for methods that can evaluate self-association propensities of concentrated mAbs at the earliest stages in antibody discovery to avoid downstream issues. We have previously developed a method (affinity-capture self-interaction nanoparticle spectroscopy, AC-SINS) that is capable of detecting weak antibody self-interactions using unusually dilute mAb solutions (tens of µg/ml).

Aromatic Methoxylation and Hydroxylation by Organometallic High-Valent Nickel Complexes.

Herein we report the synthesis and reactivity of several organometallic Ni(III) complexes stabilized by a modified tetradentate pyridinophane ligand containing one phenyl group. A room temperature stable dicationic Ni(III)-disolvento complex was also isolated, and the presence of two available cis coordination sites in this complex offers an opportunity to probe the C-heteroatom bond formation reactivity of high-valent Ni centers. Interestingly, the Ni(III)-dihydroxide and Ni(III)-dimethoxide species can be synthesized, and they undergo aryl methoxylation and hydroxylation that is favored by addition of oxidant, which also limits the β-hydride elimination side reaction.

Early safety and efficacy of percutaneous left atrial appendage suture ligation: results from the U.S. transcatheter LAA ligation consortium.

Background: Transcatheter left atrial appendage (LAA) ligation may represent an alternative to oral anticoagulation for stroke prevention in atrial fibrillation.

Objectives: This study sought to assess the early safety and efficacy of transcatheter ligation of the LAA for stroke prevention in atrial fibrillation.

Methods: This was a retrospective, multicenter study of consecutive patients undergoing LAA ligation with the Lariat device at 8 U.

Cardiac platypnea-orthodeoxia syndrome: an often unrecognized malady.

Platypnea-orthodeoxia syndrome (POS) is a rare but clinically important form of dyspnea. The syndrome is characterized by dyspnea and arterial oxygen desaturation that occurs in the upright position and improves with recumbency. In cardiac POS, an atrial septal defect or patent foramen ovale allows communication between the right- and left-sided circulations.

Organometallic nickel(III) complexes relevant to cross-coupling and carbon-heteroatom bond formation reactions.

Nickel complexes have been widely employed as catalysts in C-C and C-heteroatom bond formation reactions. In addition to Ni(0) and Ni(II) intermediates, several Ni-catalyzed reactions are proposed to also involve odd-electron Ni(I) and Ni(III) oxidation states. We report herein the isolation, structural and spectroscopic characterization, and organometallic reactivity of Ni(III) complexes containing aryl and alkyl ligands.

Sodium nitroprusside enhanced cardiopulmonary resuscitation prevents post-resuscitation left ventricular dysfunction and improves 24-hour survival and neurological function in a porcine model of prolonged untreated ventricular fibrillation.

Aim Of Study: Sodium nitroprusside-enhanced CPR, or SNPeCPR, consists of active compression-decompression CPR with an impedance threshold device, abdominal compression, and intravenous sodium nitroprusside (SNP). We hypothesize that SNPeCPR will improve post resuscitation left ventricular function and neurological function compared to standard (S) CPR after 15 min of untreated ventricular fibrillation in a porcine model of cardiac arrest.

Methods: Pigs (n = 22) anesthetized with isoflurane underwent 15 min of untreated ventricular fibrillation, were then randomized to 6 min of S-CPR (n = 11) or SNPeCPR (n = 11) followed by defibrillation.

Modifiers of symptomatic embolic risk in infective endocarditis.

Objective: To ascertain the impact of prior antiplatelet and statin therapy on symptomatic embolic events in [corrected] infective endocarditis (IE).

Patients And Methods: We studied a retrospective cohort of adult patients with a diagnosis of IE who presented to Mayo Clinic (Rochester, MN) from January 1, 2003, to December 31, 2006. Patients were grouped into those who received treatment before infection or controls who did not receive treatment for both antiplatelet therapy and, separately, statin therapy.

Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR) improves vital organ perfusion pressures and carotid blood flow in a porcine model of cardiac arrest.

Purpose Of The Study: To describe a new method of CPR that optimizes vital organ perfusion pressures and carotid blood flow. We tested the hypothesis that a combination of high dose sodium nitroprusside (SNP) as well as non-invasive devices and techniques known independently to enhance circulation would significantly improve carotid blood flow (CBF) and return of spontaneous circulation (ROSC) rates in a porcine model of cardiac arrest.

Methods: 15 isofluorane anesthetized pigs (30±1 kg), after 6 min of untreated ventricular fibrillation, were subsequently randomized to receive either 15 min of standard CPR (S-CPR) (8 animals) or 5 min epochs of S-CPR followed by active compression-decompression (ACD)+inspiratory impedance threshold device (ITD) CPR followed by ACD+ITD+abdominal binding (AB) with 1mg of SNP administered at minutes 2, 7, 12 of CPR (7 animals).

Sodium nitroprusside-enhanced cardiopulmonary resuscitation improves resuscitation rates after prolonged untreated cardiac arrest in two porcine models.

Objective: Sodium nitroprusside-enhanced cardiopulmonary resuscitation consists of active compression-decompression, an impedance threshold device, abdominal binding, and large intravenous doses of sodium nitroprusside. We hypothesize that sodium nitroprusside-enhanced cardiopulmonary resuscitation will significantly increase carotid blood flow and return of spontaneous circulation compared to standard cardiopulmonary resuscitation after prolonged ventricular fibrillation and pulseless electrical activity cardiac arrest.

Design: Prospective randomized animal study.