A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies.

Oncogenic activation of MYC in cancers predominantly involves increased transcription rather than coding region mutations. However, MYC-dependent lymphomas frequently acquire point mutations in the MYC phosphodegron, including at threonine 58 (T58), where phosphorylation permits binding via the FBW7 ubiquitin ligase triggering MYC degradation. To understand how T58 phosphorylation functions in normal cell physiology, we introduced an alanine mutation at T58 (T58A) into the endogenous c-Myc locus in the mouse germline. While MYC-T58A mice develop normally, lymphomas and myeloid leukemias emerge in ∼60% of adult homozygous T58A mice. We found that primitive hematopoietic progenitor cells from MYC-T58A mice exhibit aberrant self-renewal normally associated with hematopoietic stem cells (HSCs) and up-regulate a subset of MYC target genes important in maintaining stem/progenitor cell balance. In lymphocytes, genomic occupancy by MYC-T58A was increased at all promoters compared with WT MYC, while genes differentially expressed in a T58A-dependent manner were significantly more proximal to MYC-bound enhancers. MYC-T58A lymphocyte progenitors exhibited metabolic alterations and decreased activation of inflammatory and apoptotic pathways. Our data demonstrate that a single point mutation stabilizing MYC is sufficient to skew target gene expression, producing a profound gain of function in multipotential hematopoietic progenitors associated with self-renewal and initiation of lymphomas and leukemias.

Growing old with Myc.

The Myc proto-oncogene has been intensively studied in tumorigenesis and development. A new paper in Cell reports the role of Myc as a determinant of mammalian longevity. Myc heterozygous mice exhibit extended lifespans resulting from alterations in multiple cellular processes distinct from those observed in other longevity models.

A Vanadium Methylidene.

Examples of stable 3d transition metal methylidene complexes are extremely rare. Here we report an isolable and stable vanadium methylidene complex, [(PNP)V(=NAr)(=CH2)] (PNP = N[2-PiPr2-4-methylphenyl]-, Ar = 2,6-iPr2C6H3), via H atom transfer (HAT) from [(PNP)V(NHAr)(CH3)] or [(PNP)V(=NAr)(CH3)] using two or one equivalents of the TEMPO radical (TEMPO = (2,2,6,6-tetramethylpiperidin-1-yl)oxyl), respectively. Alternatively, the vanadium methylidene moiety can also be formed via the treatment of transient [(PNP)V=NAr] with the Wittig reagent, H2CPPh3. Structural and spectroscopic analysis, including 13C enriched labeling of the methylidene ligand, unequivocally confirmed the terminal nature of a rare 3d methylidene complex, featuring a V=CH2 bond distance of 1.908(2) Å and a highly downfield 13C NMR spectral shift at 298 ppm. In the absence of the ylide, intermediate [(PNP)V=NAr] activates dinitrogen to form an end-on bridging N2 complex, [(PNP)V(=NAr)]2(µ2-η1:η1-N2), having a singlet ground state. Complex [(PNP)V(=NAr)(=CH2)] reacts with H3COTf to form [(PNP)V(=NAr)(OTf)], accompanied by the release of ethylene as evidenced by 1H NMR spectroscopy, and reactivity studies suggest a ß-hydride elimination pathway.

Vanadium Alkylidyne Initiated Cyclic Polymer Synthesis: The Importance of a Deprotiovanadacyclobutadiene Moiety.

Reported is the catalytic cyclic polymer synthesis by a 3d transition metal complex: a V(V) alkylidyne, [(dBDI)V≡CtBu(OEt2)] (1-OEt2), supported by the deprotonated ß-diketiminate dBDI2- (dBDI2- = ArNC(CH3)CHC(CH2)NAr, Ar = 2,6-iPr2C6H3). Complex 1-OEt2 is a precatalyst for the polymerization of phenylacetylene (PhCCH) to give cyclic poly(phenylacetylene) (c-PPA), whereas its precursor, complex [(BDI)V≡CtBu(OTf)] (2-OTf; BDI- = [ArNC(CH3)]2CH, Ar = 2,6-iPr2C6H3, OTf = OSO2CF3), and the zwitterion [((C6F5)3B-dBDI)V≡CtBu(OEt2)] (3-OEt2) exhibit low catalytic activity despite having a neopentylidyne ligand. Cyclic polymer topologies were verified by size-exclusion chromatography (SEC) and intrinsic viscosity studies. A component of the mechanism of the cyclic polymerization reaction was probed by isolation and full characterization of 4- and 6-membered metallacycles as model intermediates. Metallacyclobutadiene (MCBD) and deprotiometallacyclobutadiene (dMCBD) complexes (dBDI)V[C(tBu)C(H)C(tBu)] (4-tBu) and (BDI)V[C(tBu)CC(Mes)] (5-Mes), respectively, were synthesized upon reaction with bulkier alkynes, tBu- (tBuCCH) and Mes-acetylene (MesCCH), with 1-OEt2. Furthermore, the reaction of the conjugate acid of 1-OEt2, [(BDI)V≡CtBu(OTf)] (2-OTf), with the conjugated base of phenylacetylene, lithium phenylacetylide (LiCCPh), yields the doubly deprotio-metallacycle complex, [Li(THF)4]{(BDI)V[C(Ph)CC(tBu)CC(Ph)]} (6). Protonation of the doubly deprotio-metallacycle complex 6 yields 6-H+, a catalytically active species toward the polymerization of PhCCH, for which the polymers were also confirmed to be cyclic by SEC studies. Computational mechanistic studies complement the experimental observations and provide insight into the mechanism of cyclic polymer growth. The noninnocence of the supporting dBDI2- ligand and its role in proton shuttling to generate deprotiometallacyclobutadiene (dMCBD) complexes that proposedly culminate in the formation of catalytically active V(III) species are also discussed. This work demonstrates how a dMCBD moiety can react with terminal alkynes to form cyclic polyalkynes.

A multifunctional role for riboflavin in the yellow nectar of Capsicum baccatum and Capsicum pubescens.

A few Capsicum (pepper) species produce yellow-colored floral nectar, but the chemical identity and biological function of the yellow pigment are unknown. A combination of analytical biochemistry techniques was used to identify the pigment that gives Capsicum baccatum and Capsicum pubescens nectars their yellow color. Microbial growth assays, visual modeling, and honey bee preference tests for artificial nectars containing riboflavin were used to assess potential biological roles for the nectar pigment. High concentrations of riboflavin (vitamin B2) give the nectars their intense yellow color. Nectars containing riboflavin generate reactive oxygen species when exposed to light and reduce microbial growth. Visual modeling also indicates that the yellow color is highly conspicuous to bees within the context of the flower. Lastly, field experiments demonstrate that honey bees prefer artificial nectars containing riboflavin. Some Capsicum nectars contain a yellow-colored vitamin that appears to play roles in (1) limiting microbial growth, (2) the visual attraction of bees, and (3) as a reward to nectar-feeding flower visitors (potential pollinators), which is especially interesting since riboflavin is an essential nutrient for brood rearing in insects. These results cumulatively suggest that the riboflavin found in some Capsicum nectars has several functions.

Bifunctional Ligands: Evaluating the Role of Acidic Protons in the Secondary Coordination Sphere.

To evaluate bifunctional ligand reactivity involving NH acidic sites in the secondary coordination sphere, complexes where the proton has been substituted with a methyl group (NMe) are often investigated. An alternative strategy involves substitution of the NH group for an O. This contribution considers and compares the merits of these approaches; the synthesis and characterization of cationic square-planar Rh carbonyl complexes bearing diprotic bispyrazole pyridine ligand L1, and the bis-methylated pyrazole pyridine ligand L1Me are described. The syntheses and characterization of the novel monoprotic pyrazole isoxazole pyridine ligand L2 and aprotic bisisoxazole pyridine ligand L3, and their corresponding Rh carbonyl complexes are also described. Comparison of the CO stretching frequencies of the four Rh complexes suggest that substitutions of NH with NMe, as well as with O, lead to significant electronic differences. These electronic differences result in different reactivities with respect to ligand addition/substitution of the Rh carbonyl complexes. Overall, the data suggest that electronic differences arising due to the NH substitutions can be significant and should be considered when the NH group is substituted in investigations of the participation of the NH proton in a reaction.

The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.

Male germ cell (GC) production is a metabolically driven and apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss of Mlx results in altered metabolism as well as activation of multiple stress pathways and GC apoptosis in the testes. This is concomitant with dysregulation of the expression of male-specific GC transcripts and proteins. Our genomic and functional analyses identify loci directly bound by MLX involved in these processes, including metabolic targets, obligate components of male-specific GC development, and apoptotic effectors. These in vivo and in vitro studies implicate MLX and other members of the proximal MYC network, such as MNT, in regulation of metabolism and differentiation, as well as in suppression of intrinsic and extrinsic death signaling pathways in both spermatogenesis and male germ cell tumors (MGCTs).

Controlling the Size of Molecular Copper Clusters Supported by a Multinucleating Macrocycle.

The use of a nonrigid, pyridyldialdimine-derived macrocyclic ligand (3PDAI2) enabled the synthesis of well-defined mono-, di-, tri-, and tetra-nuclear Cu(I) complexes in good yields through rational synthetic means. Starting from mono- and diargentous 3PDAI2 complexes, transmetalation to Cu(I) proceeded smoothly with formation of AgX (X = Cl, I) salts to generate mono-, di-, and trinuclear copper complexes. Monodentate supporting ligands (MeCN, xylNC, PMe3, PPh3) were found to either transmetallate with or bind various di- and trinuclear clusters. The solution-phase dynamic behaviors of these species were studied through NMR spectroscopic investigations, and an in-depth study of the trinuclear systems revealed a rate dependence on the identity of the supporting ligand, indicating that ligand dissociation reactions were involved in the dynamic exchange processes. Synthetic investigations further found methods for the purposeful interconversion between the di- and trinuclear systems as well as the synthesis of a pseudotetrahedral tetracopper complex with two µ-Ph supporting ligands.

Metal-Ligand Redox Cooperativity in Cerium Amine-/Amido-Phenolate-Type Complexes.

The synthesis and characterization of two cerium complexes of redox-active amine/amido-phenolate-type ligands are reported. A tripodal framework comprising the tris(2-(3',5'-di-tert-butyl-2'-hydroxyphenyl)amino-phenyl) amine (H6Clamp) proligand was synthesized for comparison of its cerium complex with a potassium-cerium heterobimetallic complex of the 4,6-di-tert-butyl-2-[(2,6-diisopropylphenyl)imino]quinone (dippap) proligand. Structural studies indicate differences in the cerium(III) cation coordination spheres, where CeIII(CH3CN)1.5(H3Clamp) (1-Ce(H3Clamp)) exhibits shorter Ce-O distances and longer Ce-N bond distances compared to the analogous distances in K3(THF)3CeIII(dippap)3 (2-Ce(ap)), due to the gross structural differences between the systems. Differences are also evident in the temperature-dependent magnetic properties, where smaller χT products were observed for 2-Ce(ap) compared to 1-Ce(H3Clamp). Solution electrochemical studies for the complexes were interpreted based on ligand- and metal-based oxidation events, and the cerium(III) oxidation of 2-Ce(ap) was observed to be more facile than that of 1-Ce(H3Clamp), behavior that was cautiously attributed to the rigidity of the encrypted 1-Ce(H3Clamp) complex compared to the heterobimetallic framework of 2-Ce(ap). These results contribute to the understanding of how ligand designs can promote facile redox cycling for cerium complexes of redox-active ligands, given the large contraction of cerium-ligand bonds upon oxidation.

The current standard of the shoulder trauma series in Ireland - A national audit.

OBJECTIVES/AIMS: The primary aim of this study was to assess the current standard of shoulder radiographs in Ireland. The secondary aim of this study was to determine whether orthopaedic surgeons in Ireland are of the opinion that a national protocol is required, and what this protocol should consist of. METHODS: A national audit of shoulder trauma series x-rays performed in emergency departments was conducted. The number and type of views performed was recorded. The anteroposterior (AP) and axillary or Velpeau views were assessed to determine if they met pre-defined audit criteria. Consultant orthopaedic surgeons working in public trauma hospitals were invited to participate in an online survey by email. RESULTS: The number of shoulder trauma series included in this audit was 789. The majority of patients had two views performed (75.92%, n â€‹= â€‹599) and 21.17% (n â€‹= â€‹167) had an axillary or Velpeau view. The AP view met the audit criteria in 23.09% (n â€‹= â€‹181) of cases. The survey response rate was 70.8% (n â€‹= â€‹17). 88.2% (n â€‹= â€‹15) of surgeons agreed that three views should be performed for a shoulder trauma series and 94.12% (n â€‹= â€‹16) agreed that an axillary or Velpeau view should be included. The majority of surgeons surveyed (94%, n â€‹= â€‹16) are in favour of establishing a national protocol. CONCLUSION: The current standard shoulder trauma series in Irish hospitals consists of two views, most frequently a thoracic AP and a scapular Y view. We propose the introduction of a national protocol consisting of three views: Grashey AP, Scapular Y, and an axillary or Velpeau view.

Computer vision model for the detection of canine pododermatitis and neoplasia of the paw.

BACKGROUND: Artificial intelligence (AI) has been used successfully in human dermatology. AI utilises convolutional neural networks (CNN) to accomplish tasks such as image classification, object detection and segmentation, facilitating early diagnosis. Computer vision (CV), a field of AI, has shown great results in detecting signs of human skin diseases. Canine paw skin diseases are a common problem in general veterinary practice, and computer vision tools could facilitate the detection and monitoring of disease processes. Currently, no such tool is available in veterinary dermatology. ANIMALS: Digital images of paws from healthy dogs and paws with pododermatitis or neoplasia were used. OBJECTIVES: We tested the novel object detection model Pawgnosis, a Tiny YOLOv4 image analysis model deployed on a microcomputer with a camera for the rapid detection of canine pododermatitis and neoplasia. MATERIALS AND METHODS: The prediction performance metrics used to evaluate the models included mean average precision (mAP), precision, recall, average precision (AP) for accuracy and frames per second (FPS) for speed. RESULTS: A large dataset labelled by a single individual (Dataset A) used to train a Tiny YOLOv4 model provided the best results with a mean mAP of 0.95, precision of 0.86, recall of 0.93 and 20 FPS. CONCLUSIONS AND CLINICAL RELEVANCE: This novel object detection model has the potential for application in the field of veterinary dermatology.

Metallacyclobuta-(2,3)-diene: A Bidentate Ligand for Stream-line Synthesis of First Row Transition Metal Catalysts for Cyclic Polymerization of Phenylacetylene.

Described here is a direct entry to two examples of 3d transition metal catalysts that are active for the cyclic polymerization of phenylacetylene, namely, [(BDI)M{κ2 -C,C-(Me3 SiC3 SiMe3 )}] (2-M) (BDI=[ArNC(CH3 )]2 CH- , Ar=2,6-i Pr2 C6 H3 ; M=Ti, V). Catalysts are prepared in one step by the treatment of [(BDI)MCl2 ] (1-M, M=Ti, V) with 1,3-dilithioallene [Li2 (Me3 SiC3 SiMe3 )]. Complexes 2-M have been spectroscopically and structurally characterized and the polymers that are catalytically formed from phenylacetylene were verified to have a cyclic topology based on a combination of size-exclusion chromatography (SEC) and intrinsic viscosity studies. Two-electron oxidation of 2-V with nitrous oxide (N2 O) cleanly yields a [VV ] alkylidene-alkynyl oxo complex [(BDI)V(=O){κ1 -C-(=C(SiMe3 )CC(SiMe3 ))}] (3), which lends support for how this scaffold in 2-M might be operating in the polymerization of the terminal alkyne. This work demonstrates how alkylidynes can be circumvented using 1,3-dianionic allene as a segue into M-C multiple bonds.

Synthesis and Characterization of a Bridging Cerium(IV) Nitride Complex.

Complexes featuring lanthanide-ligand multiple bonds are rare and highly reactive. They are important synthetic targets to understand 4f/5d-bonding in comparison to d-block and actinide congeners. Herein, the isolation and characterization of a bridging cerium(IV)-nitride complex: [(TriNOx)Ce(Li2µ-N)Ce(TriNOx)][BArF4] is reported, the first example of a molecular cerium-nitride. The compound was isolated by deprotonating a monometallic cerium(IV)-ammonia complex: [CeIV(NH3)(TriNOx)][BArF4]. The average Ce═N bond length of [(TriNOx)Ce(Li2µ-N)Ce(TriNOx)][BArF4] was 2.117(3) Å. Vibrational studies of the 15N-isotopomer exhibited a shift of the Ce═N═Ce asymmetric stretch from ν = 644 cm-1 to 640 cm-1, and X-ray spectroscopic studies confirm the +4 oxidation state of cerium. Computational analyses showed strong involvement of the cerium 4f shell in bonding with overall 16% and 11% cerium weight in the σ- and π-bonds of the Ce═N═Ce fragment, respectively.

Mediating Photochemical Reaction Rates at Lewis Acidic Rare Earths by Selective Energy Loss to 4f-Electron States.

Manifesting chemical differences in individual rare earth (RE) element complexes is challenging due to the similar sizes of the tripositive cations and the corelike 4f shell. We disclose a new strategy for differentiating between similarly sized Dy3+ and Y3+ ions through a tailored photochemical reaction of their isostructural complexes in which the f-electron states of Dy3+ act as an energy sink. Complexes RE(hfac)3(NMMO)2 (RE = Dy (2-Dy) and Y (2-Y), hfac = hexafluoroacetylacetonate, and NMMO = N-methylmorpholine-N-oxide) showed variable rates of oxygen atom transfer (OAT) to triphenylphosphine under ultraviolet (UV) irradiation, as monitored by 1H and 19F NMR spectroscopies. Ultrafast transient absorption spectroscopy (TAS) identified the excited state(s) responsible for the photochemical OAT reaction or lack thereof. Competing sensitization pathways leading to excited-state deactivation in 2-Dy through energy transfer to the 4f electron manifold ultimately slows the OAT reaction at this metal cation. The measured rate differences between the open-shell Dy3+ and closed-shell Y3+ complexes demonstrate that using established principles of 4f ion sensitization may deliver new, selective modalities for differentiating the RE elements that do not depend on cation size.

Silica Supported Organometallic IrI Complexes Enable Efficient Catalytic Methane Borylation.

Catalytic C-H borylation is an attractive method for the conversion of the most abundant hydrocarbon, methane (CH4), to a mild nucleophilic building block. However, existing CH4 borylation catalysts often suffer from low turnover numbers and conversions, which is hypothesized to result from inactive metal hydride agglomerates. Herein we report that the heterogenization of a bisphosphine molecular precatalyst, [(dmpe)Ir(cod)CH3], onto amorphous silica dramatically enhances its performance, yielding a catalyst that is 12-times more efficient than the current standard for CH4 borylation. The catalyst affords over 2000 turnovers at 150 °C in 16 h with a selectivity of 91.5% for mono- vs diborylation. Higher catalyst loadings improve yield and selectivity for the monoborylated product (H3CBpin) with 82.8% yield and >99% selectivity being achieved with 1255 turnovers. X-ray absorption and dynamic nuclear polarization-enhanced solid-state NMR spectroscopic studies identify the supported precatalyst as an IrI species, and indicate that upon completion of catalysis, multinuclear Ir polyhydrides are not formed. This is consistent with the hypothesis that immobilization of the organometallic Ir species on a surface prevents bimolecular decomposition pathways. Immobilization of the homogeneous IrI fragment onto amorphous silica represents a unique and simple strategy to improve the TON and longevity of a CH4 borylation catalyst.

Electronic Structure Studies and Photophysics of Luminescent Th(IV) Anilido and Imido Complexes.

A series of thorium anilide compounds [ThNHArR(TriNOx)] (R = para-OCH3 (1-ArOMe), para-H (1-ArH), para-Cl (1-ArCl), para-CF3 (1-Ar4-CF3), TriNOx3- = tris(2-tert-butylhydroxylaminato)benzylamine), and their corresponding imido compounds [Li(DME)][Th═NArR(TriNOx)] (2-ArR) as well as the alkyl congeners [ThNHAd(TriNOx)] (1-Ad) and [Li(DME)][Th═NAd(TriNOx)] (2-Ad), have been prepared. The para-substituents on the arylimido moiety were introduced for systematic variation of their electron-donating and withdrawing abilities, changes that were evident in measurements of the 13C{1H} NMR chemical shifts of the ipso-C atom of the ArR moiety. Room temperature, solution-state luminescence of the four new thorium imido compounds, along with the previously reported [Li(THF)2][Th═NAr3,5-CF3(TriNOx)] (2-Ar3,5-CF3) and [Li(THF)(Et2O)][Ce═NAr3,5-CF3(TriNOx)] (3-Ar3,5-CF3) have been described. Among these complexes, 2-Ar3,5-CF3 demonstrated the most intense luminescence feature with excitation at 398 nm and emission at 453 nm. The luminescence measurements, together with a time-dependent density functional theory (TD-DFT) study, helped uncover an intra-ligand n → π* transition that was assigned as the origin of the bright blue luminescence; 3-Ar3,5-CF3 has an 1.2 eV redshift in excitation energy compared with its proligand. The weak luminescence of other derivatives (2-ArR and 3-Ar3,5-CF3) was attributed to non-radiative decay from low-lying excited states originating from inter-ligand transitions (2-ArR) or ligand-to-metal charge transfer bands (3-Ar3,5-CF3). Overall, the results expand the range of the thorium imido organometallic compounds and demonstrate that thorium(IV) complexes can support strong ligand luminescence. The results also demonstrate the utility of applying a Th(IV) center for tuning the n → π* luminescence energy and intensity of an associated imido moiety.

Investigating Metal-Metal Bond Polarization in a Heteroleptic Tris-Ylide Diiron System.

This article describes the synthesis, characterization, and S-atom transfer reactivity of a series of C3v-symmetric diiron complexes. The iron centers in each complex are coordinated in distinct ligand environments, with one (FeN) bound in a pseudo-trigonal bipyramidal geometry by three phosphinimine nitrogens in the equatorial plane, a tertiary amine, and the second metal center (FeC). FeC is coordinated, in turn, by FeN, three ylidic carbons in a trigonal plane, and, in certain cases, by an axial oxygen donor. The three alkyl donors at FeC form through the reduction of the appended N═PMe3 arms of the monometallic parent complex. The complexes were studied crystallographically, spectroscopically (NMR, UV-vis, and Mössbauer), and computationally (DFT, CASSCF) and found to be high-spin throughout, with short Fe-Fe distances that belie weak orbital overlap between the two metals. Further, the redox nature of this series allowed for the determination that oxidation is localized to the FeC. S-atom transfer chemistry resulted in the formal insertion of a S atom into the Fe-Fe bond of the reduced diiron complex to form a mixture of Fe4S and Fe4S2 products.

Observing Similarities and Differences in the Properties of Isostructural Niobium(V)/Tantalum(V) Coordination Compounds with Strong Pi-Donor Ligands.

While niobium and tantalum are found together in their mineral ores, their respective applications in technology require chemical separation. Nb/Ta separations are challenging due to the similar reactivities displayed by these metals in the solution phase. Coordination complexes of these metals have been studied in the contexts of catalysis, small-molecule activation, and functional group insertion reactivity; relatively few studies exist directly comparing the properties of isostructural Nb/Ta complexes. Such comparisons advance the development of Nb/Ta separation chemistry through the potential for differential reactivity. Here, we explore fundamental physicochemical properties in extensively characterized Nb/Ta coordination complexes [Na(DME)3][MClamp], (Clamp6- = tris-(2-(3',5'-di-tert-butyl-2'-oxyphenyl)amidophenyl)amine; M = Nb, Ta) to advance the understanding of the different electronic, optical, and excited-state properties that these metals exhibit in pi-loaded coordination complexes.

Cyclic ß-hydroxy-α-nitrosulfone isomers readily interconvert via open-chain aldehyde forms.

Two structurally diverse cyclic ß-hydroxy-α-nitrosulfones have been prepared and their isomerisation reactions studied. These cyclic ß-hydroxy-α-nitrosulfones undergo isomer equilibration via open-chain aldehyde forms under a variety of mild conditions. Michael condensation of 1,1'-[(1,3-dinitro-1,3-propanediyl)bis(sulfonyl)]bis(benzene) with propenal and subsequent cyclisation afforded 2,4-dinitro-2,4-bis(phenylsulfonyl)cyclohexanol in 98% yield as a mixture of four diastereomers. Sequential chromatography and recrystallization afford pure (1R,2R,4S)-rel-2,4-dinitro-2,4-bis(phenylsulfonyl)cyclohexanol based on spectroscopic and X-ray crystallographic data. This diastereomer equilibrates with the other three possible diastereomers under a variety of mild conditions: during silica gel chromatography, when dissolved in basic solution, and when dissolved in neutral polar solvents. Open-chain aldehyde forms are implicated as intermediates in isomer interconversion. Condensation of 1-methyl-4-[(nitromethyl)sulfonyl]benzene and pentanedial gives 2-(4-methylphenylsulfonyl)-2-nitrocyclohexane-1,3-diol as predominantly two diastereomers. Purification affords pure racemic diastereomer in 55% yield. This racemic diastereomer interconverts with several other isomers during silica gel chromatography. These isomers were identified as one, likely two, diastereomeric meso 2-(4-methylphenylsulfonyl)-2-nitrocyclohexane-1,3-diol isomers and four cyclic hemiacetal constitutional isomers. When dissolved in neutral polar solvents, the racemic diastereomer also interconverts with meso diastereomers and cyclic hemiacetals showing a marked solvent dependence. Reaction of the racemic diastereomer with triethylamine in dichloromethane results in isomerisation as well as substantial reversion to 1-methyl-4-[(nitromethyl)sulfonyl]benzene and pentanedial. Reaction with triethylamine in DMSO as well as simply warming in DMSO results in ring opening and concomitant dehydration to afford (E)-6-(4-methylphenylsulfonyl)-6-nitrohex-4-enal.

Arthroscopic Rotator Cuff Repair Results in Improved Clinical Outcomes and Low Revision Rates at 10-Year Follow-Up: A Systematic Review.

PURPOSE: To study the literature to evaluate the functional outcomes, radiologic outcomes, and revision rates following arthroscopic rotator cuff repair (ARCR) at a minimum of 10-years follow-up. METHODS: Two independent reviewers performed a literature search of PubMed, Embase, and Scopus using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Only studies reporting on outcomes of ARCR with a minimum 10-year follow-up were considered for inclusion. Patient demographics, satisfaction, and clinical, radiologic, and surgical outcomes were evaluated. RESULTS: Our search found 9 studies including 455 shoulders in 448 patients (51.6% male patients), with age at time of surgery ranging from 45 to 90 years met our inclusion criteria. Overall follow-up ranged from 10 to 18 years. At final follow-up, the ranges of American Shoulder & Elbow Surgeons, age- and sex-adjusted Constant-Morley, and University of California Los Angeles scores were reported in 5, 6, and 3 studies, respectively, as 79.4 to 93.2, 73.2 to 94, and 26.5 to 33, respectively. Of the included studies, satisfaction rates varied in 6 studies from 85.7% to 100% in the long-term. Additionally, the overall radiologic retear rate ranged from 9.5% to 63.2%. The overall surgical revision rates ranged in 6 studies from 3.8% to 15.4%, with from 0% to 6.7% requiring revision ARCR and from 1.0% to 3.6% requiring revision subacromial decompression in 6 and 2 studies, respectively, at minimum 10-years' follow-up. CONCLUSIONS: In this study, we found that ARCR results in high rates of patient satisfaction, satisfactory clinical outcomes with respect to patient-reported functional outcomes and range of motion, and low revision rates at minimum 10-years' follow-up. However, an overall 30% retear rate was observed in asymptomatic patients. LEVEL OF EVIDENCE: Level IV, systematic review of Level II-IV studies.