Epigenetic Induction of Smooth Muscle Cell Phenotypic Alterations in Aortic Aneurysms and Dissections.

BACKGROUND: Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes in AAD tissues and the mechanisms driving SMC phenotypic alterations remain to be identified. METHODS: We examined the transcriptomic and epigenomic dynamics of aortic SMC phenotypic changes in mice with angiotensin II-induced AAD by using single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin. SMC phenotypic alteration in aortas from patients with ascending thoracic AAD was examined by using single-cell RNA sequencing analysis. RESULTS: Single-cell RNA sequencing analysis revealed that aortic stress induced the transition of SMCs from a primary contractile phenotype to proliferative, extracellular matrix-producing, and inflammatory phenotypes. Lineage tracing showed the complete transformation of SMCs to fibroblasts and macrophages. Single-cell sequencing assay for transposase-accessible chromatin analysis indicated that these phenotypic alterations were controlled by chromatin remodeling marked by the reduced chromatin accessibility of contractile genes and the induced chromatin accessibility of genes involved in proliferation, extracellular matrix, and inflammation. IRF3 (interferon regulatory factor 3), a proinflammatory transcription factor activated by cytosolic DNA, was identified as a key driver of the transition of aortic SMCs from a contractile phenotype to an inflammatory phenotype. In cultured SMCs, cytosolic DNA signaled through its sensor STING (stimulator of interferon genes)-TBK1 (tank-binding kinase 1) to activate IRF3, which bound and recruited EZH2 (enhancer of zeste homolog 2) to contractile genes to induce repressive H3K27me3 modification and gene suppression. In contrast, double-stranded DNA-STING-IRF3 signaling induced inflammatory gene expression in SMCs. In Sting-/- mice, the aortic stress-induced transition of SMCs into an inflammatory phenotype was prevented, and SMC populations were preserved. Finally, profound SMC phenotypic alterations toward diverse directions were detected in human ascending thoracic AAD tissues. CONCLUSIONS: Our study reveals the dynamic epigenetic induction of SMC phenotypic alterations in AAD. DNA damage and cytosolic leakage drive SMCs from a contractile phenotype to an inflammatory phenotype.

An analysis of publications originating from abstracts presented at the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Meeting.

BACKGROUND: Research presentation has benefits, including CV building, networking, and collaboration. A measurable standard for achievement is publication in a peer-reviewed journal. Expectations regarding the likelihood of publication are unknown for studies presented at a national surgical scientific meeting. This study aims to evaluate predictors of manuscript publication arising from abstracts presented at a national surgical scientific meeting. METHODS: Abstracts presented at the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Meeting 2019 were reviewed. Identification of published manuscripts was completed using MedLine, Embase, and Google Scholar 28 months after the presentation to allow for time for publication. Factors evaluated for association with publication included author and abstract measures. Descriptive analyses and multivariable statistics were performed. RESULTS: 724 abstracts (160 podiums, 564 posters) were included. Of the podium presentations, 128 (80%) were published in a median of 4 months after the presentation. On univariable and multivariable analyses, there was no association between publication and abstract topic, gender, degree, number of publications, or H-indices of first and senior authors. 154 (27.3%) poster presentations were published with a median of 13 months. On univariable analysis, there was a statistically significant difference regarding the abstract topic (p = 0.015) and senior author degree (p = 0.01) between published and unpublished posters. Multivariable analysis demonstrated that colorectal surgery (OR 2.52; CI 1.02-6.23) and metabolic/obesity (OR 2.53; CI 1.09-5.84) are associated with an increased odd of publication. There was an inverse association with female senior authors (OR 0.53; CI 0.29-0.98), while additional degrees (e.g., doctorate and/or master's degree) of the senior authors were associated with an increased publication rate (OR 1.80; CI 1.00-3.22). CONCLUSION: 80% of podiums but only 27% of posters were ultimately published. While some predictors of poster publication were noted, it is unclear if these are why these projects fail to publish. Future research is warranted to determine if there are effective strategies to increase poster publication rates.

Factors Associated with Receipt of Adjuvant Chemotherapy in Stage II Colon Cancer.

BACKGROUND: The benefits of chemotherapy in stage II colon cancer remain unclear, but it is recommended for high-risk stage II disease. Which patients receive chemotherapy and its impact on survival remains undetermined. METHODS: The National Cancer Database was surveyed between 2004 and 2016 for stage II colon cancer patients. Patients were categorized as high- or average-risk as defined by the National Comprehensive Cancer Network. The demographic characteristics of high- and average-risk patients who did and did not receive chemotherapy were compared using univariate and multivariable analyses. The survival of high- and average-risk patients was compared based on receipt of chemotherapy with Cox hazard ratios and Kaplan-Meier curves. RESULTS: Overall, 84,424 patients met the inclusion criteria. A total of 34,868 patients were high-risk and 49,556 were average-risk. In high-risk patients, the risk factors for not receiving chemotherapy included increasing age, distance from the treatment facility, Charlson-Deyo score, and lack of insurance. In average-risk patients, factors associated with receipt of chemotherapy were decreasing age, distance from the treatment facility, Charlson-Deyo score, and non-academic association of the treatment facility. In both, chemotherapy was significantly associated with increased survival on the Kaplan-Meier curve. In the Cox hazard ratio, only high-risk patients benefited from chemotherapy (hazard ratio 1.183, confidence interval 1.116-1.254). CONCLUSIONS: Factors associated with not receiving chemotherapy in high-risk stage II colon cancers included increasing age, medical comorbidities, increasing distance from the treatment facility, and lack of insurance. Chemotherapy is associated with improved overall survival in high-risk patients.

Contemporary Etiologies, Outcomes, and Novel Risk Score for Isolated Tricuspid Regurgitation.

OBJECTIVES: The authors report etiologies and outcomes and devise a risk model in a large contemporary cohort of patients with isolated tricuspid regurgitation (TR). BACKGROUND: Isolated TR is a challenging clinical entity with heterogeneous etiology and often poor outcomes, with a paucity of recent research regarding the epidemiology of isolated TR. METHODS: Consecutive patients with isolated TR graded at least moderate to severe on echocardiography from January 2004 to December 2018 (n = 9,045, mean age 70.4 ± 15.4 years, 60.3% women) were studied. TR etiologies were individually adjudicated as secondary or primary, with subcategories. All-cause death during follow-up was the primary endpoint, with associations between etiology and outcomes analyzed and a risk model created. RESULTS: Primary and secondary TR etiologies were present in 470 (5.2%) and 8,575 (94.8%) patients, respectively. The main secondary etiologies were left heart disease in 4,664 (54.4%), atrial functional in 2,086 (24.3%), and pulmonary disease in 1,454 (17.0%), and the main primary etiologies were endocarditis in 222 (47.2%), degenerative or prolapse in 86 (18.3%), and prosthetic valve failure in 79 (16.8%). There were 3,987 deaths (44.0%) over a mean follow-up period of 2.6 ± 3.3 years. In unadjusted analyses, patients with secondary TR had worse survival than those with primary TR (HR: 1.56; 95% CI: 1.32-1.85), but this result was not statistically significant in multivariable analysis. The authors devised and internally validated a risk score for predicting 1-year mortality in these patients. CONCLUSIONS: Secondary TR constituted 95% of isolated significant TR and conferred worse survival than primary TR in unadjusted but not adjusted analyses. The present novel risk score stratifies the risk for 1-year death and may influence decision making for management in these high-risk patients.

Excited-State Bond Contraction and Charge Migration in a Platinum Dimer Complex Characterized by X-ray and Optical Transient Absorption Spectroscopy.

Interactions between metal centers in dimeric transition metal complexes (TMCs) play important roles in their excited-state energetics and pathways and, thus, affect their photophysical properties relevant to their applications, for example, photoluminescent materials and photocatalysis. Here, we report electronic and nuclear structural dynamics studies of two photoexcited pyrazolate-bridged [Pt(ppy)(µ-R2pz)]2-type Pt(II) dimers (ppy = 2-phenylpyridine, µ-R2pz = 3,5-substituted pyrazolate): [Pt(ppy)(µ-H2pz)]2 (1) and [Pt(NDI-ppy)(µ-Ph2pz)]2 (2, NDI = 1,4,5,8-naphthalenediimide), both of which have distinct ground-state Pt-Pt distances. X-ray transient absorption (XTA) spectroscopy at the Pt LIII-edge revealed a new d-orbital vacancy due to the one-electron oxidation of the Pt centers in 1 and 2. However, while a transient Pt-Pt contraction was observed in 2, such an effect was completely absent in 1, demonstrating how the excited states of these complexes are determined by the overlap of the Pt (dz2) orbitals, which is tuned by the steric bulk of the pyrazolate R-groups in the 3- and 5-positions. In tandem with analysis of the Pt-Pt distance structural parameter, we observed photoinduced electron transfer in 2 featuring a covalently linked NDI acceptor on the ppy ligand. The formation and subsequent decay of the NDI radical anion absorption signals were detected upon photoexcitation using optical transient absorption spectroscopy. The NDI radical anion decayed on the same time scale, hundreds of picoseconds, as that of the d-orbital vacancy signal of the oxidized Pt-Pt core observed in the XTA measurements. The data indicated an ultrafast formation of the charge-separated state and subsequent charge recombination to the original Pt(II-II) species.

N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection.

The COVID-19 pandemic continues to have an unprecedented impact on societies and economies worldwide. There remains an ongoing need for high-performance SARS-CoV-2 tests which may be broadly deployed for infection monitoring. Here we report a highly sensitive single molecule array (Simoa) immunoassay in development for detection of SARS-CoV-2 nucleocapsid protein (N-protein) in venous and capillary blood and saliva. In all matrices in the studies conducted to date we observe >98% negative percent agreement and >90% positive percent agreement with molecular testing for days 1-7 in symptomatic, asymptomatic, and pre-symptomatic PCR+ individuals. N-protein load decreases as anti-SARS-CoV-2 spike-IgG increases, and N-protein levels correlate with RT-PCR Ct-values in saliva, and between matched saliva and capillary blood samples. This Simoa SARS-CoV-2 N-protein assay effectively detects SARS-CoV-2 infection via measurement of antigen levels in blood or saliva, using non-invasive, swab-independent collection methods, offering potential for at home and point of care sample collection.

Does double-blind peer review impact gender authorship trends? An evaluation of two leading neurosurgical journals from 2010 to 2019.

OBJECTIVE: Publications are key for advancement within academia. Although women are underrepresented in academic neurosurgery, the rates of women entering residency, achieving board certification, and publishing papers are increasing. The goal of this study was to assess the current status of women in academic neurosurgery publications. Specifically, this study sought to 1) survey female authorship rates in the Journal of Neurosurgery (JNS [not including JNS: Spine or JNS: Pediatrics]) and Neurosurgery from 2010 to 2019; 2) analyze whether double-blind peer review (started in Neurosurgery in 2011) altered female authorship rates relative to single-blind review (JNS); and 3) evaluate how female authorship rates compared with the number of women entering neurosurgery residency and obtaining neurosurgery board certification. METHODS: Genders of the first and last authors for JNS and Neurosurgery articles from 2010 to 2019 were obtained. Data were also gathered on the number and percentage of women entering neurosurgery residency and women obtaining American Board of Neurological Surgeons (ABNS) certification between 2010 and 2019. RESULTS: Women accounted for 13.4% (n = 570) of first authors and 6.8% (n = 240) of last authors in JNS and Neurosurgery publications. No difference in rates of women publishing existed between the two journals (first authors: 13.0% JNS vs 13.9% Neurosurgery, p = 0.29; last authors: 7.3% JNS vs 6.0% Neurosurgery, p = 0.25). No difference existed between women first or last authors in Neurosurgery before and after initiation of double-blind review (p = 0.066). Significant concordance existed between the gender of first and last authors: in publications with a woman last author, the odds of the first author being a woman was increased by twofold (OR 2.14 [95% CI 1.43-3.13], p = 0.0001). Women represented a lower proportion of authors of invited papers (8.6% of first authors and 3.1% of last authors were women) compared with noninvited papers (14.1% of first authors and 7.4% of last authors were women) (first authors: OR 0.576 [95% CI 0.410-0.794], p = 0.0004; last authors: OR 0.407 [95% CI 0.198-0.751], p = 0.001). The proportion of women US last authors (7.4%) mirrors the percentage of board-certified women neurosurgeons (5.4% in 2010 and 6.8% in 2019), while the percentage of women US first authors (14.3%) is less than that for women entering neurosurgical residency (11.2% in 2009 and 23.6% in 2018). CONCLUSIONS: This is the first report of female authorship in the neurosurgical literature. The authors found that single- versus double-blind peer review did not impact female authorship rates at two top neurosurgical journals.

Radiation-Associated Valvular Disease.

PURPOSE OF REVIEW: Radiation-associated valvular disease (RAVD) is characterized by late valvular manifestations following radiation exposure to the mediastinum. Review of current guidelines was performed to examine best practices to reduce risk and optimize outcomes in this patient population. RECENT FINDINGS: Early and consistent screening and comprehensive and careful planning are critical in managing RAVD. Due to long latency periods, serial screening and targeted evaluation of risk factors are essential to early detection. Varying and complex presentations of RAVD require an integrated team of experienced specialists equipped with multimodality imaging-based screening protocols to stratify risk, plan intervention, and evaluate treatment response. Patients with valvular manifestations associated with radiation therapy call for an individualized plan of care involving longitudinal multimodality imaging-based screening and experienced decision-making regarding timing and strategy of intervention to improve patient outcomes.

Geospatial Analysis of Neighborhood Deprivation Index (NDI) for the United States by County.

Little is known about the spatial clustering of neighborhood deprivation across the United States (U.S.). Using data from the 2010 U.S. Census Bureau, we created a neighborhood deprivation index (NDI: higher NDI indicates higher deprivation/ lower neighborhood socioeconomic status) for each county within the U.S. County level scores were loaded into ArcGIS 10.5.1 where they were mapped and analyzed using Moran's I and Anselin Local Moran's I. Ultimately, NDI varies spatially across the US. The highest NDI scores were found in the Southeastern and Southwestern U.S. states, and inland regions of Southern California. This information is critical for public health initiative development as planners may need to tailor the scale of their efforts based on the higher NDI neighborhoods of the county or geographic region with potentially greater chronic disease burden.

Intriguing Effects of Halogen Substitution on the Photophysical Properties of 2,9-(Bis)halo-Substituted Phenanthrolinecopper(I) Complexes.

Three new copper(I) complexes [Cu(LX)2]+(PF6-) (where LX stands for 2,9-dihalo-1,10-phenanthroline and X = Cl, Br, and I) have been synthesized in order to study the impact of halogen substituents tethered in the α position of the chelating nitrogen atoms on their physical properties. The photophysical properties of these new complexes (hereafter named Cu-X) were characterized in both their ground and excited states. Femtosecond ultrafast spectroscopy revealed that early photoinduced processes are faster for Cu-I than for Cu-Cl or Cu-Br, both showing similar behaviors. Their electronic absorption and electrochemical properties are comparable to benchmark [Cu(dmp)2]+ (where dmp stands for 2,9-dimethyl-1,10-phenanthroline); furthermore, their optical features were fully reproduced by time-dependent density functional theory and ab initio molecular dynamics calculations. All three complexes are luminescent at room temperature, showing that halogen atoms bound to positions 2 and 9 of phenanthroline are sufficiently bulky to prevent strong interactions between the excited Cu complexes and solvent molecules in the coordination sphere. Their behavior in the excited state, more specifically the extent of the photoluminescence efficiency and its dependence on the temperature, is, however, strongly dependent on the nature of the halogen. A combination of ultrafast transient absorption spectroscopy, temperature-dependent steady-state fluorescence spectroscopy, and computational chemistry allows one to gain a deeper understanding of the behavior of all three complexes in their excited state.

Probing the solvation structure and dynamics in ionic liquids by time-resolved infrared spectroscopy of 4-(dimethylamino)benzonitrile.

In this work we demonstrate the use of the push-pull model system 4-(dimethylamino)benzonitrile (DMABN) as a convenient molecular probe to investigate the local solvation structure and dynamics by means of time-resolved infrared spectroscopy (TRIR). The photochemical features associated with this system provide several advantages due to the high charge separation between the ground and charge transfer states involving the characteristic nitrile bond, and an excited state lifetime that is long enough to observe the slow solvation dynamics in organic solvents and ionic liquids. The conversion from a locally excited state to an intramolecular charge transfer state (LE-ICT) in ionic liquids shows similar kinetic lifetimes in comparison to organic solvents. This similarity confirms that such conversion depends solely on the intramolecular reorganization of DMABN in the excited state, and not by the dynamics of solvation. In contrast, the relative shift of the ν(CN) vibration during the relaxation of the ICT state reveals two distinct lifetimes that are sensitive to the solvent environment. This study reveals a fast time component which is attributed to the dipolar relaxation of the solvent and a slower time component related to the rotation of the dimethylamino group of DMABN.

Probing Interligand Electron Transfer in the 1MLCT S1 Excited State of trans-Mo2L2L'2 Compounds: A Comparative Study of Auxiliary Ligands and Solvents.

The interligand charge dynamics of the lowest singlet metal-to-ligand charge-transfer states (1MLCT S1 states) of a series of quadruply bonded trans-Mo2(NN)2(O2C-X)2 paddlewheel compounds are investigated, where NN is a π-accepting phenylpropiolamidinate ligand and O2C-X (X = Me, tBu, TiPB, or CF3) is an auxiliary carboxylate ligand. The compounds show strong light absorption in the visible region due to MLCT transitions from the Mo2 center to the NN ligands. The transferred electron density was followed by femtosecond time-resolved infrared (fs-TRIR) spectroscopy with vibrational reporters such as the ethynyl groups on the NN ligands. The observed fs-TRIR spectra show that these compounds have asymmetric 1MLCT S1 excited states where the transferred electron mainly resides on a single NN ligand. The presence of interligand electron transfer (ILET) is suggested to explain the shape of the ν(C≡C) bands and the influence of auxiliary ligands and solvents on the interligand electronic coupling. The ILET in the 1MLCT S1 state is shown to be sensitive to the functional groups on the auxiliary ligands while being less responsive to changes in solvents.

Can Excited State Electronic Coherence Be Tuned via Molecular Structural Modification? A First-Principles Quantum Electronic Dynamics Study of Pyrazolate-Bridged Pt(II) Dimers.

Materials and molecular systems exhibiting long-lived electronic coherence can facilitate coherent transport, opening the door to efficient charge and energy transport beyond traditional methods. Recently, signatures of a possible coherent, recurrent electronic motion were identified in femtosecond pump-probe spectroscopy experiments on a binuclear platinum complex, where a persistent periodic beating in the transient absorption signal's anisotropy was observed. In this study, we investigate the excitonic dynamics that underlie the suspected electronic coherence for a series of binuclear platinum complexes exhibiting a range of interplatinum distances. Results suggest that the long-lived coherence can only result when competitive electronic couplings are in balance. At longer Pt-Pt distances, the electronic couplings between the two halves of the binuclear system weaken, and exciton localization and recombination is favored on short time scales. For short Pt-Pt distances, electronic couplings between the states in the coherent superposition are stronger than the coupling with other excitonic states, leading to long-lived coherence.

Femtosecond Study of Dimolybdenum Paddlewheel Compounds with Amide/Thioamide Ligands: Symmetry, Electronic Structure, and Charge Distribution in the 1MLCT S1 State.

Four photophysically interesting dimolybdenum paddlewheel compounds are synthesized and characterized: I and II contain amide ligand (N,3-diphenyl-2-propynamide), and III and IV contain thioamide ligand (N,3-diphenyl-2-propynethioamide). I and III are trans-Mo2L2(O2C-TiPB)2-type compounds, and II and IV are Mo2L4-type compounds, where O2C-TiPB is 2,4,6-triisopropylbenzoate. I-IV display strong light absorption due to metal to ligand charge transfer (MLCT) transitions from molybdenum to the amide/thioamide ligands. Charge transfer dynamics in the MLCT excited states of I-IV have been examined using femtosecond transient absorption (fs-TA) spectroscopy and femtosecond time-resolved infrared (fs-TRIR) spectroscopy. The asymmetric amide/thioamide ligands show two forms of regioarrangements in the paddlewheel compounds. Analyses of the ν(C≡C) bands in the fs-TRIR spectra of I and II show similar electron density distribution over ligands in their 1MLCT S1 states where only two amide ligands are involved and the transferred electron is mainly localized on one of them. The fs-TRIR spectra of III and IV, however, show different charge distribution patterns where the transferred electron is fully delocalized over two thioamide ligands in III and partially delocalized in IV. Fast interligand electron transfer (ILET) was recognized as the explanation for the various charge distribution patterns, and ILET was shown to be influenced by both the ligands and the ligand arrangements.

Tunable Excited-State Properties and Dynamics as a Function of Pt-Pt Distance in Pyrazolate-Bridged Pt(II) Dimers.

The influence of molecular structure on excited-state properties and dynamics of a series of cyclometalated platinum dimers was investigated through a combined experimental and theoretical approach using femtosecond transient absorption (fs TA) spectroscopy and density functional theory (DFT) calculations. The molecules have the general formula [Pt(ppy)(µ-R2pz)]2, where ppy = 2-phenylpyridine, pz = pyrazolate, and R = H, Me, Ph, or (t)Bu, and are strongly photoluminescent at room temperature. The distance between the platinum centers in this A-frame geometry can be varied depending on the steric bulk of the bridging pyrazolate ligands that exert structural constraints and compress the Pt-Pt distance. At large Pt-Pt distances there is little interaction between the subunits, and the chromophore behaves similar to a monomer with excited states described as mixtures of ligand-centered and metal-to-ligand charge transfer (LC/MLCT) transitions. When the Pt(II) centers are brought closer together with bulky bridging ligands, they interact through their dz(2) orbitals and the S1 and T1 states are best characterized as metal-metal-to-ligand charge transfer (MMLCT) in character. The results of the femtoseconds TA experiments reveal that intersystem crossing (ISC) occurs on ultrafast time scales (τS1 < 200 fs), while there are two relaxation processes occurring within the triplet manifold, τ1 = 0.5-3.2 ps and τ2 = 20-70 ps; the longer time constants correspond to the presence of bulkier bridging ligands. DFT calculations illustrate that the Pt-Pt distances further contract in the T1 (3)MMLCT states; therefore, slower relaxation may be related to a larger structural reorganization. Subsequent investigations using faster time resolution are planned to measure the ISC process as well as to identify any potential coherent interaction(s) between the platinum centers that may occur.

MM Quadruply Bonded Complexes Supported by Vinylbenzoate Ligands: Synthesis, Characterization, Photophysical Properties and Application as Synthons.

From the reactions between M2(T i PB)4 compounds and meta and para - vinylbenzoic acids (2 equiv) in toluene at room temperature the compounds trans-M2(T i PB)2L2, where L = m-vinylbenzoate 1A (M = Mo) and 1B (M = W) and T i PB = 2,4,6-triisopropylbenzoate, and where L = p-vinylbenzoate 2A (M = Mo) and 2B (M = W) have been isolated. Compounds 1A and 2A have been shown to undergo Heck carbon-carbon coupling reactions with phenyliodide to produce trans-Mo2(T i PB)2(O2CC6H4-m-CH=CH-C6H5)2,3A and trans-Mo2(T i PB)2(O2CC6H4-p-CH=CH-C6H5)2, 4A. The molybdenum compounds 1A and 2A have been structurally characterized by single crystal X-ray crystallography. All the new compounds have been characterized by 1H NMR, IR, UV-Visible absorption and emission spectroscopy, high resolution MALDITOF MS, fs- and ns- transient absorption spectroscopy and fs- time-resolved IR spectroscopy. Electronic structure calculations employing density functional theory, DFT, and time-dependent DFT have been employed to aid in the interpretation of spectral data. All compounds show intense absorptions in the visible region corresponding to M2δ to Lπ* charge transfer transitions. The lifetimes of the 1MLCT state fall in the range of 1 - 10 ps and for the molybdenum complexes the T1 states are 3δδ* with lifetimes ~50 µs while for the tungsten complexes the T1 are 3 MLCT with lifetimes in the range of 3 - 10 ns.

Photophysical studies of metal to ligand charge transfer involving quadruply bonded complexes of molybdenum and tungsten.

Photoinduced metal-to-ligand charge transfer transitions afford numerous applications in terms of photon energy harvesting. The majority of metal complexes studied to date involve diamagnetic systems of d(6), d(8), and d(10) transition metals. These typically have very short-lived, ∼100 fs, singlet metal to ligand charge transfer ((1)MLCT) states that undergo intersystem crossing to triplet metal to ligand charge transfer ((3)MLCT) states that are longer lived and are responsible for much of the photophysical studies. In contrast, the metal-metal quadruply bonded complexes of molybdenum and tungsten supported by carboxylate, O2CR, and related amidinate ligands (RN)2C(R') have relatively long-lived (1)MLCT states arising from M2δ to Lπ* transitions. These have lifetimes in the range 1-20 ps prior to intersystem crossing to T1 states that may be (3)MLCT or (3)MMδδ* with lifetimes of 1-100 ns and 1-100 µs, respectively. The M2 quadruply bonded complexes take the form M2L4 or M2L4-nL'n where n = 1-3. Thus, in their photoexcited MLCT states, these compounds pose the question of how the charge resides on the ligands. This Account reviews the current knowledge of how charge is positioned with time in S1 and T1 states with the aid of active IR reported groups located on the ligands, for example, C≡X multiple bonds (X = C, N, or O). Several examples of localized and delocalized charge distributions are noted along with kinetic barriers to the interconversion of MLCT and δδ* states. On the 50th anniversary of the recognition of the MM quadruple bond, these complexes are revealing some remarkable features in the study of the photophysical properties of metal-ligand charge transfer states.