Disparate reactivity of a chiral iron(II) tetracarbene complex with organic azides.

A chiral tetra-NHC iron(II) complex and its disparate reactivity with multiple organic azides is reported. Both aryl and alkyl azides react with the iron(II) complex yielding three distinct products: an iron(IV) imide, an iron(IV) tetrazene, and a surprising and unprecedented double imide insertion complex.

Integrated miRNA-mRNA networks underlie attenuation of chronic β-adrenergic stimulation-induced cardiac remodeling by minocycline.

Adverse cardiac remodeling contributes to heart failure development and progression, partly due to inappropriate sympathetic nervous system activation. Although β-adrenergic receptor (β-AR) blockade is a common heart failure therapy, not all patients respond, prompting exploration of alternative treatments. Minocycline, an FDA-approved antibiotic, has pleiotropic properties beyond antimicrobial action.

Automated radiosynthesis of [ F]CETO, a PET radiotracer for imaging adrenal glands, on Synthra RNplus.

Primary aldosteronism (PA) is the leading secondary cause of hypertension. Determining whether one (unilateral) or both (bilateral) adrenal glands are the source of PA in a patient remains challenging, and yet it is a critical step in the decision whether to recommend potentially curative surgery (adrenalectomy) or lifelong medical therapy (typically requiring multiple drugs). Recently, we have developed a fluorine-18 radiopharmaceutical [ F]CETO to permit greater access to PA molecular imaging.

Impact of Peptide Sequence on Functional siRNA Delivery and Gene Knockdown with Cyclic Amphipathic Peptide Delivery Agents.

Short-interfering RNA (siRNA) oligonucleotide therapeutics that modify gene expression by accessing RNA-interference (RNAi) pathways have great promise for the treatment of a range of disorders; however, their application in clinical settings has been limited by significant challenges in cellular delivery. Herein, we report a structure-function study using a series of modified cyclic amphipathic cell-penetrating peptides (CAPs) to determine the impact of peptide sequence on (1) siRNA-binding efficiency, (2) cellular delivery and knockdown efficiency, and (3) the endocytic uptake mechanism. Nine cyclic peptides of the general sequence Ac-C[XZ]CG-NH in which X residues are hydrophobic/aromatic (Phe, Tyr, Trp, or Leu) and Z residues are charged/hydrophilic (Arg, Lys, Ser, or Glu) are assessed along with one acyclic peptide, Ac-(WR)G-NH.

Empowering self-critical perfectionistic students: A waitlist controlled feasibility trial of an explanatory feedback intervention on daily coping processes.

This study of 176 university students tested a single-session explanatory feedback intervention (EFI), derived from the perfectionism coping processes model. Participants with higher self-critical perfectionism completed daily measures of stress appraisals, coping, and affect for 7 days. A randomized control design was used to compare an EFI condition with a waitlist control condition over 4 weeks with individualized feedback delivered one-on-one by student trainees in-person or remotely through videoconferencing.

Multi-omic analysis of the cardiac cellulome defines a vascular contribution to cardiac diastolic dysfunction in obese female mice.

Coronary microvascular dysfunction (CMD) is associated with cardiac dysfunction and predictive of cardiac mortality in obesity, especially in females. Clinical data further support that CMD associates with development of heart failure with preserved ejection fraction and that mineralocorticoid receptor (MR) antagonism may be more efficacious in obese female, versus male, HFpEF patients. Accordingly, we examined the impact of smooth muscle cell (SMC)-specific MR deletion on obesity-associated coronary and cardiac diastolic dysfunction in female mice.

Chronic high-rate pacing induces heart failure with preserved ejection fraction-like phenotype in Ossabaw swine.

The lack of pre-clinical large animal models of heart failure with preserved ejection fraction (HFpEF) remains a growing, yet unmet obstacle to improving understanding of this complex condition. We examined whether chronic cardiometabolic stress in Ossabaw swine, which possess a genetic propensity for obesity and cardiovascular complications, produces an HFpEF-like phenotype. Swine were fed standard chow (lean; n = 13) or an excess calorie, high-fat, high-fructose diet (obese; n = 16) for ~ 18 weeks with lean (n = 5) and obese (n = 8) swine subjected to right ventricular pacing (180 beats/min for ~ 4 weeks) to induce heart failure (HF).

Validation of a combined image derived input function and venous sampling approach for the quantification of [F]GE-179 PET binding in the brain.

Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma.

Snake Bite Management: A Scoping Review of the Literature.

Background: Around the world, snake bite envenomation remains an underreported human health hazard. Envenomation can cause local and systemic complications, especially when there is a lack of antivenom availability. Although there are established guidelines regarding snake bite management acute care, there is a paucity of data regarding surgical intervention and the plastic surgeon's role treating this unique patient population.

Reversion inducing cysteine rich protein with Kazal motifs and cardiovascular diseases: The RECKlessness of adverse remodeling.

The Reversion Inducing Cysteine Rich Protein With Kazal Motifs (RECK) is a glycosylphosphatidylinositol (GPI) anchored membrane-bound regulator of matrix metalloproteinases (MMPs). It is expressed throughout the body and plays a role in extracellular matrix (ECM) homeostasis and inflammation. In initial studies, RECK expression was found to be downregulated in various invasive cancers and associated with poor prognostic outcome.

Emotional and interpersonal mechanisms in community SSRI treatment of social anxiety disorder.

Background: Affective and interpersonal behavioural patterns characteristic of social anxiety disorder show improvement during treatment with serotonin agonists (e.g., selective serotonin reuptake inhibitors), commonly used in the treatment of social anxiety disorder.

Automated radiosynthesis of [ C]UCB-J for imaging synaptic density by positron emission tomography.

An automated radiosynthesis of carbon-11 positron emission tomography radiotracer [ C]UCB-J for imaging the synaptic density biomarker synaptic vesicle glycoprotein SV2A was established using Synthra RNPlus synthesizer. Commercially available trifluoroborate UCB-J analogue was used as a radiolabelling precursor, and the desired radiolabelled product was isolated in 11 ± 2% (n = 7) nondecay corrected radiochemical yield and formulated as a 10% EtOH solution in saline with molar activities of 20 to 100 GBq/μmol. The method was based upon the palladium(0)-mediated Suzuki cross-coupling reaction and [ C]CH I as a radiolabelling synthon.

Implementation of Bar-Code Medication Administration to Reduce Patient Harm.

Objective: To assess the impact of implementing bar-code medication administration (BCMA) technology on the rate of medication administration errors in the inpatient setting, specifically those that affect the patient and result in harm.

Patients And Methods: Implementation of the new technology began in September 2008 in a staged rollout of 4 or 5 units at a time in 11 separate waves. All corresponding medication administrations and voluntarily reported medication-related adverse events from March 1, 2007, through September 30, 2013, were included for analyses.

Affect, interpersonal behaviour and interpersonal perception during open-label, uncontrolled paroxetine treatment of people with social anxiety disorder: a pilot study.

Background: Laboratory-based research with community samples has suggested changes in affective, behavioural and cognitive processes as possible explanations for the effects of serotonergic medications. Examining the effects of serotonergic medications using an ecological momentary measure (such as event-contingent recording) in the daily lives of people with social anxiety disorder would contribute to establishing the effects of these medications on affect, behaviour and one form of cognition: perception of others’ behaviour.

Methods: The present study assessed changes in affect, interpersonal behaviour and perception of others’ behaviour in adults with social anxiety disorder using ecological momentary assessment at baseline and over 4 months of a single-arm, uncontrolled, open-label trial of treatment with the selective serotonin reuptake inhibitor paroxetine.

Major Comorbidities of Atopic Dermatitis: Beyond Allergic Disorders.

The consequences of atopic dermatitis reach beyond the skin and past childhood. Patients with atopic dermatitis are at risk of developing allergic comorbidities, but less is known about the associations between atopic dermatitis and non-allergic conditions. Understanding these non-allergic comorbidities has the potential to improve patient outcomes and to help mitigate the cost and burdens associated with these conditions.

GreenCut protein CPLD49 of Chlamydomonas reinhardtii associates with thylakoid membranes and is required for cytochrome b f complex accumulation.

The GreenCut encompasses a suite of nucleus-encoded proteins with orthologs among green lineage organisms (plants, green algae), but that are absent or poorly conserved in non-photosynthetic/heterotrophic organisms. In Chlamydomonas reinhardtii, CPLD49 (Conserved in Plant Lineage and Diatoms49) is an uncharacterized GreenCut protein that is critical for maintaining normal photosynthetic function. We demonstrate that a cpld49 mutant has impaired photoautotrophic growth under high-light conditions.

Search for Neutrinoless Double-Beta Decay with the Upgraded EXO-200 Detector.

Results from a search for neutrinoless double-beta decay (0νββ) of ^{136}Xe are presented using the first year of data taken with the upgraded EXO-200 detector. Relative to previous searches by EXO-200, the energy resolution of the detector has been improved to σ/E=1.23%, the electric field in the drift region has been raised by 50%, and a system to suppress radon in the volume between the cryostat and lead shielding has been implemented.

Non-model model organisms.

Model organisms are widely used in research as accessible and convenient systems to study a particular area or question in biology. Traditionally only a handful of organisms have been widely studied, but modern research tools are enabling researchers to extend the set of model organisms to include less-studied and more unusual systems. This Forum highlights a range of 'non-model model organisms' as emerging systems for tackling questions across the whole spectrum of biology (and beyond), the opportunities and challenges, and the outlook for the future.

Allostatic load and comorbidities: A mitochondrial, epigenetic, and evolutionary perspective.

Stress-related pathophysiology drives comorbid trajectories that elude precise prediction. Allostatic load algorithms that quantify biological "wear and tear" represent a comprehensive approach to detect multisystemic disease processes of the mind and body. However, the multiple morbidities directly or indirectly related to stress physiology remain enigmatic.

Impact of personality psychopathology on outcome in short-term cognitive-behavioral therapy for Axis I disorders.

Cognitive behavioral therapy (CBT) is efficacious for many Axis I disorders, though its effectiveness in the real world, for patients with Axis II comorbidity is less well known. This study examines the effectiveness of CBT for Axis I disorders in three groups of patients: those with personality disorders, those with personality disorder traits and those with no Axis II pathology. Consecutive referrals of patients with non-psychotic Axis I disorders were assessed for short-term CBT in a University Teaching Unit.

Translating Atopic Dermatitis Management Guidelines Into Practice for Primary Care Providers.

Atopic dermatitis affects a substantial number of children, many of whom seek initial treatment from their pediatrician or other primary care provider. Approximately two-thirds of these patients have mild disease and can be adequately managed at the primary care level. However, recent treatment guidelines are written primarily for use by specialists and lack certain elements that would make them more useful to primary care providers.

Performance of charged aerosol detection with hydrophilic interaction chromatography.

The performance of the charged aerosol detector (CAD) was investigated using a diverse set of 29 solutes, including acids, bases and neutrals, over a range of mobile phase compositions, particularly with regard to its suitability for use in hydrophilic interaction chromatography (HILIC). Flow injection analysis was employed as a rapid method to study detector performance. CAD response was 'quasi-universal', strong signals were observed for compounds that have low volatility at typical operating (room) temperature.

Comparison of peak shape in hydrophilic interaction chromatography using acidic salt buffers and simple acid solutions.

The retention and peak shape of neutral, basic and acidic solutes was studied on hydrophilic interaction chromatography (HILIC) stationary phases that showed both strong and weak ionic retention characteristics, using aqueous-acetonitrile mobile phases containing either formic acid (FA), ammonium formate (AF) or phosphoric acid (PA). The effect of organic solvent concentration on the results was also studied. Peak shape was good for neutrals under most mobile phase conditions.

Predicting who benefits most from cognitive-behavioral therapy for anxiety and depression.

Objectives: We examined core features of patient suitability for cognitive-behavioral therapy (CBT) and their ability to predict CBT outcomes.

Method: A sample of 256 outpatients diagnosed with depression and anxiety disorders were assessed using the Suitability for Short-Term Cognitive Therapy (SSCT) scale. Therapists rated patients' symptom severity using the Clinical Global Impression scale before and after therapy.

Understanding heterogeneity in social anxiety disorder: dependency and self-criticism moderate fear responses to interpersonal cues.

Objective: This study examined how the personality traits of self-criticism and dependency moderated the effects of situational interpersonal cues on fear during interpersonal interactions among individuals with social anxiety disorder (SAD). We hypothesized that self-criticism would moderate the fear-inducing effects of situational self-consciousness and that dependency would moderate the fear-inducing effects of situational emotional insecurity.

Methods: Forty SAD patients (Mage = 29.