General Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides and Lactams.

An iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3 + 2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using 1 mol% Vaska's complex [IrCl(CO)(PPh)] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent regio- and diastereoselective, inter- and intramolecular dipolar cycloaddition reactions with variously substituted electron-deficient alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures.

Long-term Association of Altmetric Attention Scores With Citations in Selected Major Pharmacy Journals.

To determine the long-term change in the Altmetric Attention Score (AAS) and its components, as well as the impact of higher AAS on citation count for articles published in major pharmacy journals. This study evaluated articles from pharmacy journals ranked in the top 10% according to their AAS in the year 2017. Correlation between the AAS and number of citations (through November 2020) was assessed using the Spearman's correlation test.

Computational Study of Triphosphine-Ligated Cu(I) Catalysts for Hydrogenation of CO to Formate.

The catalyzed hydrogenation of CO to formate via a triphosphine-ligated Cu(I) was studied computationally at the density functional theory level in the presence of a self-consistent reaction field. Of the four functionals benchmarked, M06 was generally in the best agreement with the available experimentally estimated values. Two bases, DBU and TBD, were studied in the context of two proposed mechanisms in the MeCN solvent.

Prediction of An(III)/Ln(III) Separation by 1,2,4-Triazinylpyridine Derivatives.

The effect of frustrated Lewis donors on metal selectivity between actinides and lanthanides was studied using a series of novel organic ligands. Structures and thermodynamic energies were predicted in the gas phase, in water, and in butanol using 9-coordinate, explicitly solvated (HO) Eu, Gd, Am, and Cm in the +III oxidation state as reactants in the formation of complexes with 2-(6-[1,2,4]-triazin-3-yl-pyridin-2-yl)-1-indole (Core 1), 3-[6-(2-pyrazol-3-yl)pyridin-2-yl]-1,2,4-triazine (Core 2), and several derivatives. These complexations were studied using density functional theory (DFT) incorporating scalar relativistic effects on the actinides and lanthanides using a small core pseudopotential and corresponding basis set.

A General Iridium-Catalyzed Reductive Dienamine Synthesis Allows a Five-Step Synthesis of Catharanthine via the Elusive Dehydrosecodine.

A new reductive strategy for the stereo- and regioselective synthesis of functionalized isoquinuclidines has been developed. Pivoting on the chemoselective iridium(I)-catalyzed reductive activation of β,γ-unsaturated δ-lactams, the efficiently produced reactive dienamine intermediates readily undergo [4 + 2] cycloaddition reactions with a wide range of dienophiles, resulting in the formation of bridged bicyclic amine products. This new synthetic approach was extended to aliphatic starting materials, resulting in the efficient formation of cyclohexenamine products, and readily applied as the key step in the shortest (five-step) total synthesis of vinca alkaloid catharanthine to date, proceeding via its elusive biosynthetic precursor, dehydrosecodine.

Prolonged cadmium exposure alters benign uterine fibroid cell behavior, extracellular matrix components, and TGFB signaling.

The heavy metal Cadmium (Cd), a widespread environmental contaminant, poses serious hazards to human health and is considered a metallohormone and carcinogen. In women with uterine fibroids, there is a significant association between blood Cd levels and increased fibroid tumor size. The aim of this study was to determine if benign human uterine leiomyoma (fibroid) cells could be malignantly transformed in vitro by continuous Cd exposure and, if so, explore a molecular mechanism by which this could occur.

Binding and stability of MgO monomers on anatase TiO(101).

In catalysis, MgO is often used to modify the acid-base properties of support oxides and to stabilize supported metal atoms and particles on oxides. In this study, we show how the sublimation of MgO powder can be used to deposit MgO monomers, hither on anatase TiO(101). A combination of x-ray electron spectroscopy, high-resolution scanning tunneling microscopy, and density functional theory is employed to gain insight into the MgO monomer binding, electronic and vibrational properties, and thermal stability.

Hydrolysis of Small Oxo/Hydroxo Molecules Containing High Oxidation State Actinides (Th, Pa, U, Np, Pu): A Computational Study.

The energetics of hydrolysis reactions for high oxidation states of oxo/hydroxo monomeric actinide species (ThO, PaO, UO, PaO(OH), UO(OH), UO, NpO, NpO(OH), and PuO(OH)) were calculated at the CCSD(T) level. The first step is the formation of a Lewis acid/base adduct with HO (hydration), followed by a proton transfer to form a dihydroxide molecule (hydrolysis); this process is repeated until all oxo groups are hydrolyzed. The physisorption (hydration) for each HO addition was predicted to be exothermic, ca.

Work-related stress: the impact of COVID-19 on critical care and redeployed nurses: a mixed-methods study.

Introduction: We need to understand the impact of COVID-19 on critical care nurses (CCNs) and redeployed nurses and National Health Service (NHS) organisations.

Methods And Analysis: This is a mixed-methods study (QUANT-QUAL), underpinned by a theoretical model of occupational stress, the Job Demand-Resources Model (JD-R). Participants are critical care and redeployed nurses from Scottish and three large English units.

An ounce of prevention is worth a pound of cure: considerations for pharmacists delivering the National Diabetes Prevention Program.

Prediabetes is highly prevalent in the United States affecting over 88 million adults. In 2010, the Centers for Disease Control and Prevention (CDC) established the National Diabetes Prevention Program (NDPP), an intensive lifestyle program consisting of a 16-lesson curriculum focused on diet, exercise, and behavior modification, with the ultimate goal to reduce progression from prediabetes to diabetes. Despite tens of millions of adults potentially qualifying to participate in the program, the uptake of the NDPP has been exceedingly low.

Induced hypernatremia in patients with moderate-to-severe ARDS: a randomized controlled study.

Background: Induced hypernatremia and hyperosmolarity is protective in animal models of lung injury. We hypothesized that increasing and maintaining plasma sodium between 145 and 150 mmol/l in patients with moderate-to-severe ARDS would be safe and will reduce lung injury. This was a prospective randomized feasibility study in moderate-to-severe ARDS, comparing standard care with intravenous hypertonic saline to achieve and maintain plasma sodium between 145 and 150 mmol/l for 7 days (HTS group).

Formation of Surface Impurities on Lithium-Nickel-Manganese-Cobalt Oxides in the Presence of CO and HO.

Surface impurities involving parasitic reactions and gas evolution contribute to the degradation of high Ni content LiNiMnCoO (NMC) cathode materials. The transient kinetic technique of temporal analysis of products (TAP), density functional theory, and infrared spectroscopy have been used to study the formation of surface impurities on varying nickel content NMC materials (NMC811, NMC622, NMC532, NMC433, NMC111) in the presence of CO and HO. CO reactivity on a clean surface as characterized by CO conversion rate in the TAP reactor follows the order: NMC811 > NMC622 > NMC532 > NMC433 > NMC111.

General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams*.

An iridium-catalyzed reductive three-component coupling reaction for the synthesis of medicinally relevant α-amino 1,3,4-oxadiazoles from abundant tertiary amides or lactams, carboxylic acids, and (N-isocyanimino) triphenylphosphorane, is described. Proceeding under mild conditions using (<1 mol %) Vaska's complex (IrCl(CO)(PPh ) ) and tetramethyldisiloxane to access the key reactive iminium ion intermediates, a broad range of α-amino 1,3,4-oxadiazole architectures were accessed from carboxylic acid feedstock coupling partners. Extension to α-amino heterodiazole synthesis was readily achieved by exchanging the carboxylic acid coupling partner for C-, S-, or N-centered Brønsted acids, and provided rapid and modular access to these desirable, yet difficult-to-access, heterocycles.

Effect of Canagliflozin Compared With Sitagliptin on Serum Lipids in Patients with Type 2 Diabetes Mellitus and Heart Failure with Reduced Ejection Fraction: A Post-Hoc Analysis of the CANA-HF Study.

The sodium glucose co-transporter 2 inhibitors have demonstrated favorable effects on cardiovascular and renal disease; however, they may also increase low-density lipoprotein cholesterol (LDL-C). There are limited data directly comparing the effects of sodium glucose co-transporter 2inhibitors on serum lipids to other antihyperglycemic therapies. In this post-hoc analysis of the CANA-HF trial, we sought to compare the effects of canagliflozin to sitagliptin in patients with type 2 diabetes mellitus (T2DM) and heart failure and reduced ejection fraction (HFrEF).

Comparisons among rainbow trout, Oncorhynchus mykiss, populations of maternal transcript profile associated with egg viability.

Background: Transcription is arrested in the late stage oocyte and therefore the maternal transcriptome stored in the oocyte provides nearly all the mRNA required for oocyte maturation, fertilization, and early cleavage of the embryo. The transcriptome of the unfertilized egg, therefore, has potential to provide markers for predictors of egg quality and diagnosing problems with embryo production encountered by fish hatcheries. Although levels of specific transcripts have been shown to associate with measures of egg quality, these differentially expressed genes (DEGs) have not been consistent among studies.

Summary of the Proceedings of the Basic Science of Uterine Fibroids Meeting: New Developments February 28, 2020.

Scientists from multiple basic disciplines and an international group of physician-scientists from the field of obstetrics and gynecology presented recent studies and discussed new and evolving theories of uterine fibroid etiology, growth and development at The Basic Science of the Uterine Fibroids meeting, sponsored by the Campion Fund and the National Institute of Environmental Health Sciences. The purpose was to share up-to date knowledge and to stimulate new concepts regarding the basic molecular biology and pathophysiology of uterine fibroids, and to promote future collaborations. The meeting was held at the National Institute of Environmental Health Sciences in North Carolina on February 28, 2020.

Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones.

The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described.

Time of eating and cardiorespiratory fitness in patients with heart failure with preserved ejection fraction and obesity.

Background And Aims: Our objective was to examine the impact of caloric intake before or after the mean time of evening meal on cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity.

Methods And Results: Twelve patients with HFpEF and obesity completed a cardiorespiratory exercise test to measure CRF, defined as peak oxygen consumption (VO). Three five-pass 24-h dietary recalls were performed for each participant and mean evening meal time was determined for each participant individually as well as the group.

The Association Between Psychological Factors and Outcomes After Distal Radius Fracture.

Purpose: The aim of this study was to identify psychological factors associated with pain intensity and disability following distal radius fracture.

Methods: We prospectively followed 216 adult patients with distal radius fracture for 9 months. Demographics, injury and treatment details, and psychological measures (Hospital Anxiety and Depression Score [HADS], Pain Catastrophizing Scale, Posttraumatic Stress Disorder Checklist-Civilian, Tampa Scale for Kinesiophobia, Illness Perception Questionnaire Brief [IPQB], General Self-Efficacy Scale, and Recovery Locus of Control [RLOC]) were collected at enrollment.

Healthcare provider characteristics that influence the implementation of individual-level patient-centered outcome measure (PROM) and patient-reported experience measure (PREM) data across practice settings: a protocol for a mixed methods systematic review with a narrative synthesis.

Background: Substantial literature has highlighted the importance of patient-reported outcome and experience measures (PROMs and PREMs, respectively) to collect clinically relevant information to better understand and address what matters to patients. The purpose of this systematic review is to synthesize the evidence about how healthcare providers implement individual-level PROMs and PREMs data into daily practice.

Methods: This mixed methods systematic review protocol describes the design of our synthesis of the peer-reviewed research evidence (i.

A modular and divergent approach to spirocyclic pyrrolidines.

An efficient three-step sequence to afford a valuable class of spirocyclic pyrrolidines is reported. A reductive cleavage/Horner-Wadsworth-Emmons cascade facilitates the spirocyclisation of a range of isoxazolines bearing a distal β-ketophosphonate. The spirocyclisation precursors are elaborated in a facile and modular fashion, a [3 + 2]-cycloaddition followed by the condensation of a phosphonate ester, introducing multiple points of divergence.

Unsupervised Machine Learning for Identifying Challenging Behavior Profiles to Explore Cluster-Based Treatment Efficacy in Children With Autism Spectrum Disorder: Retrospective Data Analysis Study.

Background: Challenging behaviors are prevalent among individuals with autism spectrum disorder; however, research exploring the impact of challenging behaviors on treatment response is lacking.

Objective: The purpose of this study was to identify types of autism spectrum disorder based on engagement in different challenging behaviors and evaluate differences in treatment response between groups.

Methods: Retrospective data on challenging behaviors and treatment progress for 854 children with autism spectrum disorder were analyzed.

The impact of medication side effects on adherence and persistence to hormone therapy in breast cancer survivors: A qualitative systematic review and thematic synthesis.

Background: Hormone Therapy (HT) reduces the risk of breast cancer recurrence and mortality in women with breast cancer. Despite these clinical benefits, rates of HT non-adherence and non-persistence are high. Research suggests this may be due to the impact of HT side effects.

Digital Health in the Management of Pediatric Growth Hormone Therapy - 10 Years of Developments.

Growth hormone administration is approved for use in a number of growth failure conditions in children. Optimal growth outcome requires continuous daily injections over many years, leading to problems of persistence and adherence with therapy. The easypod™ connect ecosystem enables electronic monitoring of injection and dose history, transmitted to a secure cloud database via the internet or cellular networks.