Understanding the role of negative charge in the scaffold of an artificial enzyme for CO hydrogenation on catalysis.

We have approached the construction of an artificial enzyme by employing a robust protein scaffold, lactococcal multidrug resistance regulator, LmrR, providing a structured secondary and outer coordination spheres around a molecular rhodium complex, [Rh(PNP)]. Previously, we demonstrated a 2-3 fold increase in activity for one Rh-LmrR construct by introducing positive charge in the secondary coordination sphere. In this study, a series of variants was made through site-directed mutagenesis where the negative charge is located in the secondary sphere or outer coordination sphere, with additional variants made with increasingly negative charge in the outer coordination sphere while keeping a positive charge in the secondary sphere.

Implementation of a High-Value, Evidence-Based Care Program: Impact and Opportunities for Learning Organizations.

Goal: Value-based care is not simply a matter of cost, but also one of outcomes and harms per dollar spent. This definition encompasses three key components: healthcare delivery that is organized around patients' medical conditions, costs and outcomes that are actively and consistently measured, and information technology that enables the other two components. Our objective in this project was to implement and measure a systemwide high-value, evidence-based care initiative with five pillars of high-value practices.

Is Access to Optimal Concussion Care for Pediatric Athletes Limited by Geography?

Objective: To evaluate access to optimal concussion care based on a pediatric patients' geography; the hypothesis is that differential access across the Unites States exists.

Design: Employed a novel strategy using internet searches to find local care, mimicking what families might do in different parts of the country.

Setting: Virtual internet searches.

Acridine photocatalysis enables tricomponent direct decarboxylative amine construction.

Amines are centrally important motifs in medicinal chemistry and biochemistry, and indispensable intermediates and linchpins in organic synthesis. Despite their cross-disciplinary prominence, synthetic access to amine continues to rely on two-electron approaches based on reductions and additions of organometallic reagents, limiting their accessible chemical space and necessitating stepwise preassembly of synthetic precursors. We report herein a homogeneous photocatalytic tricomponent decarboxylative radical-mediated amine construction that enables modular access to α-branched secondary amines directly from the broad and structurally diverse chemical space of carboxylic acids in a tricomponent reaction with aldehydes and aromatic amines.

Ketogenic diet induces p53-dependent cellular senescence in multiple organs.

A ketogenic diet (KD) is a high-fat, low-carbohydrate diet that leads to the generation of ketones. While KDs improve certain health conditions and are popular for weight loss, detrimental effects have also been reported. Here, we show mice on two different KDs and, at different ages, induce cellular senescence in multiple organs, including the heart and kidney.

Multimodal Acridine Photocatalysis Enables Direct Access to Thiols from Carboxylic Acids and Elemental Sulfur.

Development of photocatalytic systems that facilitate mechanistically divergent steps in complex catalytic manifolds by distinct activation modes can enable previously inaccessible synthetic transformations. However, multimodal photocatalytic systems remain understudied, impeding their implementation in catalytic methodology. We report herein a photocatalytic access to thiols that directly merges the structural diversity of carboxylic acids with the ready availability of elemental sulfur without substrate preactivation.

The "cesium effect" magnified: exceptional chemoselectivity in cesium ion mediated nucleophilic reactions.

Chemodivergent construction of structurally distinct heterocycles from the same precursors by adjusting specific reaction parameters is an emergent area of organic synthesis; yet, understanding of the processes that underpin the reaction divergence is lacking, preventing the development of new synthetic methods by systematically harnessing key mechanistic effects. We describe herein cesium carbonate-promoted oxadiaza excision cross-coupling reactions of β-ketoesters with 1,2,3-triazine 1-oxides that form pyridones in good to high yields, instead of the sole formation of pyridines when the same reaction is performed in the presence of other alkali metal carbonates or organic bases. The reaction can be further extended to the construction of synthetically challenging pyridylpyridones.

Cobalt-Catalyzed Carbon-Heteroatom Transfer Enables Regioselective Tricomponent 1,4-Carboamination.

Tricomponent cobalt(salen)-catalyzed carbofunctionalization of unsaturated substrates by radical-polar crossover has the potential to streamline access to broad classes of heteroatom-functionalized synthetic targets, yet the reaction platform has remained elusive, despite the well-developed analogous hydrofunctionalizations mediated by high-valent alkylcobalt intermediates. We report herein the development of a cobalt(salen) catalytic system that enables carbofunctionalization. The reaction entails a tricomponent decarboxylative 1,4-carboamination of dienes and provides a direct route to aromatic allylic amines by obviating preformed allylation reagents and protection of oxidation-sensitive aromatic amines.

Long-term follow-up of torpedo maculopathy: a case series and mini-review.

Background: Torpedo maculopathy (TM) is a rare, congenital condition characterized by an oval-shaped, chorioretinal lesion in the temporal macula of unknown etiology. To our knowledge, the longest reported follow-up of TM is 5 years. Herein we report 10 years of follow-up on two patients with TM to further characterize the long-term natural history of the condition.

Kinetically-driven reactivity of sulfinylamines enables direct conversion of carboxylic acids to sulfinamides.

Sulfinamides are some of the most centrally important four-valent sulfur compounds that serve as critical entry points to an array of emergent medicinal functional groups, molecular tools for bioconjugation, and synthetic intermediates including sulfoximines, sulfonimidamides, and sulfonimidoyl halides, as well as a wide range of other S(iv) and S(vi) functionalities. Yet, the accessible chemical space of sulfinamides remains limited, and the approaches to sulfinamides are largely confined to two-electron nucleophilic substitution reactions. We report herein a direct radical-mediated decarboxylative sulfinamidation that for the first time enables access to sulfinamides from the broad and structurally diverse chemical space of carboxylic acids.

Burn and Trauma Burden and Screening for Interpersonal Violence During the COVID-19 Pandemic.

Introduction: Nationwide shelter-in-place (SIP) orders during the pandemic have had long-lasting effects, including increased rates of domestic violence and interpersonal violence. Screening for violence varies by institution, which tool is used, and when. Given increases in burn and trauma admissions over the course of the pandemic, we sought to examine trends at our institution during this time period to better guide care and anticipate system-level effects.

Catalytic Dienylation: An Emergent Strategy for the Stereoselective Construction of Conjugated Dienes and Polyenes.

Stereoselective construction of conjugated dienes and polyenes has remained an enduring synthetic problem, due to the central roles they play in natural product synthesis, methodology, and medicine. This review focuses on the recent developments in dienylation as an emerging strategy for the direct installation of unsaturated four carbon atom units of conjugated π-systems, outlining the regio- and stereoselectivity, as well as the synthetic scope of reactions with various dienylating reagents and the mechanistic implications of the catalytic cross-coupling processes that are used to enable dienylation.

Rapid and effective fusion repair of severed digital nerves using neurorrhaphy and bioengineered solutions including polyethylene glycol: A case report.

Peripheral nerve injuries (PNIs) that consist of simple nerve severance often result in severe motor impairment and permanent loss of function. Such patients face significant costs and pose major burdens to healthcare systems. Currently, the most promising surgical technique to achieve the best clinical outcome after such PNIs is immediate primary coaptation of severed nerve ends by microsutures (neurorrhaphy).

Tricomponent Decarboxysulfonylative Cross-Coupling Facilitates Direct Construction of Aryl Sulfones and Reveals a Mechanistic Dualism in the Acridine/Copper Photocatalytic System.

Dual catalytic systems involving photocatalytic activation and transition metal-catalyzed steps have enabled innovative approaches to the construction of carbon-carbon and carbon-heteroatom bonds. However, the mechanistic complexity of the dual catalytic processes presents multiple challenges for understanding of the roles of divergent catalytic species that can impede the development of future synthetic methods. Here, we report a dual catalytic process that enables the previously inaccessible, broad-scope, direct conversion of carboxylic acids to aromatic sulfones-centrally important carbonyl group bioisosteric replacements and synthetic intermediates-by a tricomponent decarboxysulfonylative cross-coupling with aryl halides.

Reductive NO Coupling at Dicopper Center via a [Cu(NO)] Diamond-Core Intermediate.

Treatment of a dicopper(I,I) complex with excess amounts of NO leads to the formation of a dicopper dinitrosyl [Cu(NO)] complex capable of (i) releasing two equivalents of NO reversibly in 90% yield and (ii) reacting with another equivalent of NO to afford NO and dicopper nitrosyl oxo species [Cu(NO)(O)]. Resonance Raman characterization of the [Cu(NO)] complex shows a N-sensitive N═O stretch at 1527.6 cm and two Cu-N stretches at 390.

Decarboxylative Sulfinylation Enables a Direct, Metal-Free Access to Sulfoxides from Carboxylic Acids.

The intermediate oxidation state of sulfoxides is central to the plethora of their applications in chemistry and medicine, yet it presents challenges for an efficient synthetic access, limiting the structural diversity of currently available sulfoxides. Here, we report a data-guided development of direct decarboxylative sulfinylation that enables the previously inaccessible functional group interconversion of carboxylic acids to sulfoxides in a reaction with sulfinates. Given the broad availability of carboxylic acids and the growing synthetic potential of sulfinates, the direct decarboxylative sulfinylation is poised to improve the structural diversity of synthetically accessible sulfoxides.

Manganese Superoxide Dismutase Acetylation and Regulation of Protein Structure in Breast Cancer Biology and Therapy.

The loss and/or dysregulation of several cellular and mitochondrial antioxidants' expression or enzymatic activity, which leads to the aberrant physiological function of these proteins, has been shown to result in oxidative damage to cellular macromolecules. In this regard, it has been surmised that the disruption of mitochondrial networks responsible for maintaining normal metabolism is an established hallmark of cancer and a novel mechanism of therapy resistance. This altered metabolism leads to aberrant accumulation of reactive oxygen species (ROS), which, under specific physiological conditions, leads to a potential tumor-permissive cellular environment.

Protein-based models offer mechanistic insight into complex nickel metalloenzymes.

There are ten nickel enzymes found across biological systems, each with a distinct active site and reactivity that spans reductive, oxidative, and redox-neutral processes. We focus on the reductive enzymes, which catalyze reactions that are highly germane to the modern-day climate crisis: [NiFe] hydrogenase, carbon monoxide dehydrogenase, acetyl coenzyme A synthase, and methyl coenzyme M reductase. The current mechanistic understanding of each enzyme system is reviewed along with existing knowledge gaps, which are addressed through the development of protein-derived models, as described here.

Photoinduced C(sp)-H sulfination empowers the direct and chemoselective introduction of the sulfonyl group.

Direct installation of the sulfinate group by the functionalization of unreactive aliphatic C-H bonds can provide access to most classes of organosulfur compounds, because of the central position of sulfinates as sulfonyl group linchpins. Despite the importance of the sulfonyl group in synthesis, medicine, and materials science, a direct C(sp)-H sulfination reaction that can convert abundant aliphatic C-H bonds to sulfinates has remained elusive, due to the reactivity of sulfinates that are incompatible with typical oxidation-driven C-H functionalization approaches. We report herein a photoinduced C(sp)-H sulfination reaction that is mediated by sodium metabisulfite and enables access to a variety of sulfinates.

Professional identity formation for underrepresented in medicine learners.

Professional identity formation (PIF) is a dynamic developmental process by which individuals merge the knowledge and skills of clinical practice with the values and behaviors of their personal identity. For an individual physician, this process is a continuum which begins with their nascent interest in the field of medicine and extends through the end stages of a medical career. The impact of PIF has become a growing focus of medical education research in the last decade, and in that time, little attention has been paid to the influence underrepresented in medicine (UIM) identities may have on this fundamental process.

Assembly of a Genetically Encoded Artificial Metalloenzyme for Hydrogen Production.

The genetic encoding of artificial enzymes represents a substantial advantage relative to traditional molecular catalyst optimization, as laboratory-based directed evolution coupled with high-throughput screening methods can provide rapid development and functional characterization of enzyme libraries. However, these techniques have been of limited utility in the field of artificial metalloenzymes due to the need for cofactor metalation. Here, we report the development of methodology for production of nickel-substituted rubredoxin, an artificial metalloenzyme that is a structural, functional, and mechanistic mimic of the [NiFe] hydrogenases.

Repeatability of Goldmann tonometry performed by optometry students on glaucoma patients.

Background: The purpose of this study was to evaluate the repeatability of masked Goldmann tonometry performed by optometry students on patients with glaucoma.

Methods: Subjects were recruited from among patients scheduled to undergo selective laser trabeculoplasty at the Rosenberg School of Optometry clinic. Each subject had masked Goldmann tonometry performed by three examiners at each office visit: two fourth professional-year optometry interns and an attending optometrist.