Ejection fraction and ventricular volumes on rubidium positron emission tomography: Validation against cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the non-invasive gold standard for non-invasively determining left ventricular volumes (LVVs) and ejection fraction (EF). We aimed to assess the accuracy of LVV and left ventricular ejection fraction measured by positron emission tomography (PET) as compared to CMR. METHODS: Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. Analysis was performed to evaluate the agreement between the raw and body-surface-area-normalized left ventricular volume (LVV) and EF derived from PET vs. those derived from CMR. RESULTS: The study population consisted of 669 patients (mean age 62 ± 13 years, 65% male). The median (interquartile range [IQR]) duration between CMR and PET imaging was 36 (7-118) days. The median (IQR) EF values were 52% (38-63%) on CMR and 53% (37-65%) on PET (mean difference: 0.53% ± 9.1, P = 0.129) with a strong correlation (Spearman rho = 0.84, P < 0.001; Intraclass Correlation Coefficient 0.84, 95% confidence interval [CI]: 0.82-0.86, P < 0.001; Lin's concordance correlation coefficient was 0.844, 95% CI: 0.822 to 0.865). Results were similar with LVV, normalized LVV/EF, and in subgroups of patients with reduced EF, coronary artery disease scar, and LV hypertrophy as well as in patients with defibrillators. However, PET tended to underestimate LVV compared to CMR. CONCLUSION: Our analysis showed a strong correlation of EF and LVV by PET against a reference standard of CMR, whereas PET significantly underestimated LVV, but not EF, compared to CMR.

The power of zero calcium in 82-Rubidium PET irrespective of sex and age.

BACKGROUND: Despite clinical suspicion, many non-invasive tests for coronary artery disease (CAD) are normal. Coronary artery calcification score (CACS) is a well-validated method to detect and risk stratify CAD. Patients with zero calcium score (ZCS) rarely have abnormal tests. Therefore, aims were to evaluate CACS as a gatekeeper to further functional downstream testing for CAD and estimate potential radiation and cost savings. METHODS: Consecutive patients with suspected CAD referred for PET were included (n = 2640). Prevalence and test characteristics of ZCS were calculated in different groups. Summed stress score ≥ 4 was considered abnormal and summed difference score ≥ 7 equivalent to ≥ 10% ischemia. To estimate potential radiation/cost reduction, PET scans were hypothetically omitted in ZCS patients. RESULTS: Mean age was 65 ± 11 years, 46% were female. 21% scans were abnormal and 26% of patients had ZCS. CACS was higher in abnormal PET (median 561 vs 27, P < 0.001). Abnormal PET was significantly less frequent in ZCS patients (2.6% vs 27.6%, P < 0.001). Sensitivity/negative predictive value (NPV) of ZCS to detect/exclude abnormal PET and ≥ 10% ischemia were 96.8% (95%-CI 95.0%-97.9%)/97.4% (95.9%-98.3%) and 98.9% (96.7%-99.6%)/99.6% (98.7%-99.9%), respectively. Radiation and cost reduction were estimated to be 23% and 22%, respectively. CONCLUSIONS: ZCS is frequent, and most often consistent with normal PET scans. ZCS offers an excellent NPV to exclude an abnormal PET and ≥ 10% ischemia across different gender and age groups. CACS is a suitable gatekeeper before advanced cardiac imaging, and potential radiation/cost savings are substantial. However, further studies including safety endpoints are needed.

A graphite furnace-atomic absorption spectrometry-based rubidium efflux assay for screening activators of the Kv 7.2/3 channel.

For the characterization of Kv 7.2/3 channel activators, several analytical methods are available that vary in effort and cost. In addition to the technically elaborate patch-clamp method, which serves as a reference method, there exist several medium to high-throughput screening methods including a rubidium efflux flame-atomic absorption spectrometry (F-AAS) assay and a commercial thallium uptake fluorescence-based assay. In this study, the general suitability of a graphite furnace atomic absorption spectrometry (GF-AAS)-based rubidium efflux assay as a screening method for Kv 7.2/3 channel activators was demonstrated. With flupirtine serving as a reference compound, 16 newly synthesizedcompounds and the known Kv 7.2/3 activator retigabine were first classified as either active or inactive by using the GF-AAS-based rubidium (Rb) efflux assay. Then, the results were compared with a thallium (Tl) uptake fluorescence-based fluorometric imaging plate reader (FLIPR) potassium assay. Overall, 16 of 17 compounds were classified by the GF-AAS-based assay in agreement with their channel-activating properties determined by the more expensive Tl uptake, fluorescence-based assay. Thus, the performance of the GF-AAS-based Rb assay for primary drug screening of Kv 7.2/3-activating compounds was clearly demonstrated, as documented by the calculated Z'-factor of the GF-AAS-based method. Moreover, method development included optimization of the coating of the microtiter plates and the washing procedure, which extended the range of this assay to poorly adherent cells such as the HEK293 cells used in this study.

Breast-Milk Rubidium and Other Trace Elements are Associated with Neurocognitive Development in Infants at Age of 8 Months.

BACKGROUND: Trace elements may affect neurodevelopment. There is a lack of data on breast-milk rubidium (Rb) in relation to neurodevelopment in infants. The associations of copper (Cu), zinc (Zn) and strontium (Sr) with neurodevelopment in infants remain uncertain. OBJECTIVES: We sought to evaluate the associations of breast-milk Rb (primary exposure), Cu, Zn, and Sr with neurodevelopment in infants at age 8 months. METHODS: The study cohort included 117 breastfed infants. Breast-milk samples were collected at 42 days and 8 months postpartum. Breast-milk Rb, Zn, Cu, and Sr were measured by inductively coupled plasma mass spectrometer. Neurodevelopment was assessed at age 8 months. The primary outcomes were attention and working memory scores, as evaluated by the A-not-B task. Other outcomes included the Mental Development Index (MDI) and Psychomotor Development Index (PDI) as evaluated by the Bayley Scale of Infant Development III. Generalized linear models and restricted cubic spline regression were used to assess the associations between trace elements and neurodevelopment indices. Bonferroni correction was conducted on all data presented. RESULTS: A nonlinear association was observed between breast-milk Rb at 42 days and infant's attention at age 8 months (nonlinearity P = 0.037). Positive associations were observed with infant MDI scores and breast-milk Rb at 42 days (ß = 4.46; P = 0.06) and 8 months (ß = 3.79; P = 0.009) postpartum. Breast-milk Zn at 42 days was positively associated with infant's attention (ß = 0.31; P = 0.039). Sr at 42 days was positively correlated with attention (ß = 0.18; P = 0.043) and MDI scores (ß = 2.18; P = 0.015) at 8 months. Inverted U-shape associations were observed for breast-milk Cu at 42 days with infant attention and PDI scores. All associations were not significant after correction for multiple tests. CONCLUSIONS: Our data suggest that Rb, Zn, Cu, and Sr in breast milk at certain concentrations are associated with neurodevelopment in breastfed infants. Further studies are warranted to validate the findings.

Bioremediation potential of hexavalent chromium-resistant Arthrobacter globiformis 151B: study of the uptake of cesium and other alkali ions.

Cesium (Cs+) enters environments largely because of global release into the environment from weapons testing and accidents such as Fukushima Daiichi and Chernobyl nuclear waste. Even at low concentrations, Cs+ is highly toxic to ecological receptors because of its physicochemical similarity to macronutrient potassium (K+). We investigated the uptake and accumulation of Cs+ by Arthrobacter globiformis strain 151B in reference to three similar alkali metal cations rubidium (Rb+), sodium (Na+), and potassium (K+). The impact of hexavalent chromium (Cr+6) as a co-contaminant was also evaluated. A. globiformis 151B accumulated Cs+ and Cr6+ in a time-dependent fashion. In contrast, the uptake and accumulation of Rb+ did not exhibit any trends. An exposure to Cs+, Rb+, and Cr+6 triggered a drastic increase in K+ and Na+ uptake by the bacterial cells. That was followed by the efflux of K+ and Na+, suggesting a Cs+ "substitution." Two-dimensional gel-electrophoresis of bacterial cell proteomes with the following mass-spectrometry of differentially expressed bands revealed that incubation of bacterial cells with Cs+ induced changes in the expression of proteins involved in the maintenance of cellular homeostasis and reactive oxygen species removal. The ability of A. globiformis 151B to mediate the uptake and accumulation of cesium and hexavalent chromium suggests that it possesses wide-range bioremediation potential.

Optimization of the left ventricle ejection fraction estimate obtained during cardiac adenosine stress 82Rubidium-PET scanning: impact of different reconstruction protocols.

BACKGROUND: Left ventricular ejection fraction (LVEF) estimation using adenosine stress myocardial perfusion imaging (MPI) can be challenging. The short half-life of adenosine and the guideline-recommended adenosine infusion stop during Rubidium-82 acquisition protocol may affect the accuracy and repeatability of the LVEF measures. METHODS: This study comprised 25 healthy volunteers (median age 23 years) who underwent repeat myocardial perfusion imaging (MPI) sessions employing Rubidium-82 PET/CT. A guideline-recommended reconstruction protocol was used for both rest and adenosine stress MPI (150-360 s post-radiotracer injection, standardrecon). For the stress MPI protocol, two additional reconstruction protocols were considered; one was employing 60 seconds data (150-210 seconds, shortfixed) and the other a dynamic frame window based on the bolus arrival of Rubidium-82 in the heart until 210 seconds (x-210 seconds, shortindividual). We report rest and stress LVEF, the LVEF reserve, and the LVEF reserve repeatability. RESULTS: Differences in the LVEF assessments were observed between the guideline recommended and alternative reconstruction protocol (LVEF stress MPI: standardrecon = 68 ± 7%, shortfixed = 71 ± 7% (P = .08), shortindividual = 72 ± 7% (P = .04)), and the LVEF reserve was reduced for the guideline-recommended protocol (standardrecon = 7.8 ± 3.5, shortfixed = 10.1 ± 3.7, shortindividual = 10.5 ± 3.6, all P < .001). The best repeatability measures were obtained for the shortindividual protocol (repeatability: standardrecon = 45.3%, shortfixed = 41.2%, shortindividual = 31.7%). CONCLUSION: We recommend using the shortindividual reconstruction protocol for improved LVEF repeatability and reserve assessment. Alternatively, in centers with limited technical support we recommend the use of the shortfixed protocol.

Left ventricular ejection fraction, myocardial blood flow and hemodynamic variables in adenosine and regadenoson vasodilator 82-Rubidium PET.

AIMS: In most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables. METHODS AND RESULTS: Consecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P<0.001). Global rest myocardial blood flow(rMBF), stress MBF(sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in no prior CAD patients compared to prior CAD patients(1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, P<0.001) and in normal versus abnormal scans, irrespective of CAD status(no prior CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; prior CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, P<0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia (≥10%) with a negative predictive value (NPV) of 94% (CI 92-95%). CONCLUSIONS: Rest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared to normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

Prognostic value of myocardial flow reserve obtained by 82-rubidium positron emission tomography in long-term follow-up after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplantation (HTx) and non-invasive prognostic methods in long-term CAV surveillance are needed. We evaluated the prognostic value of myocardial flow reserve (MFR) obtained by 82-rubidium (82Rb) positron emission tomography (PET). METHODS: Recipients undergoing dynamic rest-stress 82Rb PET between April 2013 and June 2017 were retrospectively evaluated in a single-center study. Evaluation by PET included quantitative myocardial blood flow and semiquantitative myocardial perfusion imaging. Patients were grouped by MFR (MFR ≤ 2.0 vs MFR > 2.0) and the primary outcome was all-cause mortality. RESULTS: A total of 50 patients (68% men, median age 57 [IQR: 43 to 68]) were included. Median time from HTx to PET was 10.0 (6.7 to 16.0) years. In 58% of patients CAV was documented prior to PET. During a median follow-up of 3.6 (2.3 to 4.3) years 12 events occurred. Survival probability by Kaplan-Meier method was significantly higher in the high-MFR group (log-rank P = .02). Revascularization (n = 1), new CAV diagnosis (n = 1), and graft failure (n = 4) were more frequent in low-MFR patients. No retransplantation occurred. CONCLUSIONS: Myocardial flow reserve appears to offer prognostic value in selected long-term HTx recipients and holds promise as a non-invasive method for CAV surveillance possibly guiding management strategy.

Impact of rubidium imaging availability on management of patients with acute chest pain.

OBJECTIVE: Evaluate the impact of 82-Rubidium positron emission tomography (PET) myocardial perfusion imaging (MPI) availability on patient management presenting at the emergency department (ED) with chest pain (CP). METHODS: This is a single-center retrospective study of clinical databases. Patients presenting with CP with a non-definitive suspicion of acute coronary syndrome (ACS) at the ED between April 2016 and February 2020 were divided into 2 groups based on PET availability. The proportion of invasive coronary angiography (ICA) without significant coronary artery disease (CAD), length of stay (LoS), and additional downstream testing were evaluated. RESULTS: There were 21,242 ED visits for CP without definitive ACS: 5,492 when PET is not available and 15,750 when PET is available. When PET is available, proportion of patients undergoing a MPI study was greater (20.7% vs 17.6%, P<0.0001), proportion of ICA without significant CAD was similar (18.5% vs 21.4%, P=0.24), and median ED LoS was shorter (16.6 vs 18.1 hours, P=0.03). Patients undergoing SPECT MPI had significantly more downstream testing (8.9% vs 6.4%, P=0.003) and a higher rate of coronary angiogram without significant CAD (21.2% vs 14.2%, P=0.09) compared to those who underwent PET MPI. CONCLUSION: Availability of PET MPI was associated with an increased number of MPI referral from the ED, similar rates of ICA without significant CAD, decreased LoS, and fewer downstream testing.

OBJETIVO: Evaluar el impacto de la tomografía por emisión de positrones (PET) con 82-Rubidio y la disponibilidad de imágenes de perfusión miocárdica (MPI) en el manejo de los pacientes que se presentan en el servicio de urgencias (ED) con dolor torácico (CP). MéTODOS: Este es un estudio retrospectivo de bases de datos clínicas de un solo centro. Pacientes que presentaron CP con sospecha no definitiva de síndrome coronario agudo (ACS) en el ED entre abril de 2016 y febrero de 2020, se dividieron en 2 grupos según la disponibilidad de PET. Se evaluó la proporción de angiografía coronaria invasiva (ICA) sin enfermedad arterial coronaria (CAD) significativa, la duración de la estancia (LoS) y las pruebas posteriores adicionales. RESULTADOS: Hubo 21,242 visitas al ED por CP sin ACS definitivo: 5,492 cuando no se dispone de PET y 15.750 cuando se dispone de PET. Cuando se dispone de PET, la proporción de pacientes sometidos a estudio de MPI fue mayor (20.7% vs 17.6%, p=0.03). Los pacientes que se sometieron a SPECT MPI tuvieron significativamente más pruebas posteriores (8.9 % frente a 6.4 %, p = 0.003) y una tasa más alta de angiografía coronaria sin CAD significativa (21.2 % frente a 14.2 %, p = 0.09) en comparación con los que se sometieron a PET MPI. CONCLUSIóN: La disponibilidad de PET MPI se asoció con un mayor número de referencias de MPI desde el ED, tasas similares de ICA sin CAD significativa, disminución de LoS y menos pruebas posteriores.

Synthesis, Characterization, and Structural Analysis of AM[Al(NONDipp)(H)(SiH2Ph)] (AM = Li, Na, K, Rb, Cs) Compounds, Made Via Oxidative Addition of Phenylsilane to Alkali Metal Aluminyls.

We report the oxidative addition of phenylsilane to the complete series of alkali metal (AM) aluminyls [AM{Al(NONDipp)}]2 (AM = Li, Na, K, Rb, and Cs). Crystalline products (1-AM) have been isolated as ether or THF adducts, [AM(L)n][Al(NONDipp)(H)(SiH2Ph)] (AM = Li, Na, K, Rb, L = Et2O, n = 1; AM = Cs, L = THF, n = 2). Further to this series, the novel rubidium rubidiate, [{Rb(THF)4}2(Rb{Al(NONDipp)(H)(SiH2Ph)}2)]+ [Rb{Al(NONDipp)(H)(SiH2Ph)}2]-, was isolated during an attempted recrystallization of Rb[Al(NONDipp)(H)(SiH2Ph)] from a hexane/THF mixture. Structural and spectroscopic characterizations of the series 1-AM confirm the presence of µ-hydrides that bridge the aluminum and alkali metals (AM), with multiple stabilizing AM···π(arene) interactions to either the Dipp- or Ph-substituents. These products form a complete series of soluble, alkali metal (hydrido) aluminates that present a platform for further reactivity studies.

Divergence of the quadrupole-strain susceptibility of the electronic nematic system YbRu2Ge2.

Ferroquadrupole order associated with local [Formula: see text] atomic orbitals of rare-earth ions is a realization of electronic nematic order. However, there are relatively few examples of intermetallic materials which exhibit continuous ferroquadrupole phase transitions, motivating the search for additional materials that fall into this category. Furthermore, it is not clear a priori whether experimental approaches based on transport measurements which have been successfully used to probe the nematic susceptibility in materials such as the Fe-based superconductors will be as effective in the case of [Formula: see text] intermetallic materials, for which the important electronic degrees of freedom are local rather than itinerant and are consequently less strongly coupled to the charge-carrying quasiparticles near the Fermi energy. In the present work, we demonstrate that the intermetallic compound [Formula: see text] exhibits a tetragonal-to-orthorhombic phase transition consistent with ferroquadrupole order of the Yb ions and go on to show that elastoresistivity measurements can indeed provide a clear window on the diverging nematic susceptibility in this system. This material provides an arena in which to study the causes and consequences of electronic nematicity.

Associations of multiple plasma metals with chronic kidney disease in patients with diabetes.

As common contaminants, metals are non-negligible risk factors for diabetes and chronic kidney disease. However, whether there is an association between multiple metals exposure and incident chronic kidney disease (CKD) risk in patients with diabetes is unclear. We conducted a prospective study to evaluate these associations. In total, 3071 diabetics with baseline estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 from the Dongfeng-Tongji cohort were included. We measured baseline plasma concentrations of 23 metals and investigated the associations between plasma metal concentrations and CKD in diabetics using logistic regression, the least absolute shrinkage and selection operator (LASSO), and the Bayesian Kernel Machine Regression (BKMR) models. During average 4.6 years of follow-up, 457 diabetics developed CKD (14.9 %). The three models consistently found plasma levels of zinc, arsenic, and rubidium had a positive association with incident CKD risk in patients with diabetes, while titanium, cadmium, and lead had an inverse correlation. The results of BKMR showed a significant and positive overall effect of 23 metals on the risk of CKD, when all of the metals were above the 50th percentile as compared to the median value. In addition, potential interactions of zinc and arsenic, zinc and cadmium, zinc and lead, titanium and arsenic, and cadmium and lead on CKD risk were observed. In summary, we found significant associations of plasma titanium, zinc, arsenic, rubidium, cadmium, and lead with CKD in diabetes and interactions between these metals except for rubidium. Co-exposure to multiple metals was associated with increased CKD risk in diabetics.

Investigating Rubidium Density and Temperature Distributions in a High-Throughput 129Xe-Rb Spin-Exchange Optical Pumping Polarizer.

Accurate knowledge of the rubidium (Rb) vapor density, [Rb], is necessary to correctly model the spin dynamics of 129Xe-Rb spin-exchange optical pumping (SEOP). Here we present a systematic evaluation of [Rb] within a high-throughput 129Xe-Rb hyperpolarizer during continuous-flow SEOP. Near-infrared (52S1/2→52P1/2 (D1)/52P3/2 (D2)) and violet (52S1/2→62P1/2/62P3/2) atomic absorption spectroscopy was used to measure [Rb] within 3.5 L cylindrical SEOP cells containing different spatial distributions and amounts of Rb metal. We were able to quantify deviation from the Beer-Lambert law at high optical depth for D2 and 62P3/2 absorption by comparison with measurements of the D1 and 62P1/2 absorption lines, respectively. D2 absorption deviates from the Beer-Lambert law at [Rb]D2>4×1017 m−3 whilst 52S1/2→62P3/2 absorption deviates from the Beer-Lambert law at [Rb]6P3/2>(4.16±0.01)×1019 m−3. The measured [Rb] was used to estimate a 129Xe-Rb spin exchange cross section of γ'=(1.2±0.1)×10−21 m3 s−1, consistent with spin-exchange cross sections from the literature. Significant [Rb] heterogeneity was observed in a SEOP cell containing 1 g of Rb localized at the back of the cell. While [Rb] homogeneity was improved for a greater surface area of the Rb source distribution in the cell, or by using a Rb presaturator, the measured [Rb] was consistently lower than that predicted by saturation Rb vapor density curves. Efforts to optimize [Rb] and thermal management within spin polarizer systems are necessary to maximize potential future enhancements of this technology.

Selectivity filter instability dominates the low intrinsic activity of the TWIK-1 K2P K+ channel.

Two-pore domain K+ (K2P) channels have many important physiological functions. However, the functional properties of the TWIK-1 (K2P1.1/KCNK1) K2P channel remain poorly characterized because heterologous expression of this ion channel yields only very low levels of functional activity. Several underlying reasons have been proposed, including TWIK-1 retention in intracellular organelles, inhibition by posttranslational sumoylation, a hydrophobic barrier within the pore, and a low open probability of the selectivity filter (SF) gate. By evaluating these potential mechanisms, we found that the latter dominates the low intrinsic functional activity of TWIK-1. Investigating this further, we observed that the low activity of the SF gate appears to arise from the inefficiency of K+ in stabilizing an active (i.e. conductive) SF conformation. In contrast, other permeant ion species, such as Rb+, NH4+, and Cs+, strongly promoted a pH-dependent activated conformation. Furthermore, many K2P channels are activated by membrane depolarization via an SF-mediated gating mechanism, but we found here that only very strong nonphysiological depolarization produces voltage-dependent activation of heterologously expressed TWIK-1. Remarkably, we also observed that TWIK-1 Rb+ currents are potently inhibited by intracellular K+ (IC50 = 2.8 mm). We conclude that TWIK-1 displays unique SF gating properties among the family of K2P channels. In particular, the apparent instability of the conductive conformation of the TWIK-1 SF in the presence of K+ appears to dominate the low levels of intrinsic functional activity observed when the channel is expressed at the cell surface.

C-H Activation by RuCo3O4 Oxo Cubanes: Effects of Oxyl Radical Character and Metal-Metal Cooperativity.

High-valent multimetallic-oxo/oxyl species have been implicated as intermediates in oxidative catalysis involving proton-coupled electron transfer (PCET) reactions, but the reactive nature of these oxo species has hindered the development of an in-depth understanding of their mechanisms and multimetallic character. The mechanism of C-H oxidation by previously reported RuCo3O4 cubane complexes bearing a terminal RuV-oxo ligand, with significant oxyl radical character, was investigated. The rate-determining step involves H atom abstraction (HAA) from an organic substrate to generate a Ru-OH species and a carbon-centered radical. Radical intermediates are subsequently trapped by another equivalent of the terminal oxo to afford isolable radical-trapped cubane complexes. Density functional theory (DFT) reveals a barrierless radical combination step that is more favorable than an oxygen-rebound mechanism by 12.3 kcal mol-1. This HAA reactivity to generate organic products is influenced by steric congestion and the C-H bond dissociation energy of the substrate. Tuning the electronic properties of the cubane (i.e., spin density localized on terminal oxo, basicity, and redox potential) by varying the donor ability of ligands at the Co sites modulates C-H activations by the RuV-oxo fragment and enables construction of structure-activity relationships. These results reveal a mechanistic pathway for C-H activation by high-valent metal-oxo species with oxyl radical character and provide insights into cooperative effects of multimetallic centers in tuning PCET reactivity.

Rubidium chloride modulated the fecal microbiota community in mice.

BACKGROUND: The microbiota plays an important role in host health. Although rubidium (Rb) has been used to study its effects on depression and cancers, the interaction between microbial commensals and Rb is still unexplored. To gain the knowledge of the relationship between Rb and microbes, 51 mice receiving RbCl-based treatment and 13 untreated mice were evaluated for their characteristics and bacterial microbiome changes. RESULTS: The 16S ribosomal RNA gene sequencing of fecal microbiota showed that RbCl generally maintained fecal microbial community diversity, while the shifts in fecal microbial composition were apparent after RbCl exposure. RbCl significantly enhanced the abundances of Rikenellaceae, Alistipes, Clostridium XlVa and sulfate-reducing bacteria including Deltaproteobacteria, Desulfovibrionales, Desulfovibrionaceae and Desulfovibrio, but significantly inhibited the abundances of Tenericutes, Mollicutes, Anaeroplasmatales, Anaeroplasmataceae and Anaeroplasma lineages. With regarding to the archaea, we only observed two less richness archaea Sulfolobus and Acidiplasma at the genus level. CONCLUSIONS: Changes of fecal microbes may in part contribute to the anticancer or anti-depressant effects of RbCl. These findings further validate that the microbiome could be a target for therapeutic intervention.

A new method for detecting Na+ , K+ -ATPase activity by ICP-MS: Quantitative analysis on the inhibitory effect of rhein on Na+ , K+ -ATPase activity by ICP-MS in HCT116 cells.

Rhein is an active component from Chinese herbal medicine. It can cause diarrhea by inhibiting Na+ , K+ -ATPase activity on intestinal epithelial cells, thus decreasing the re-absorption of Na+ from intestinal tract to blood. However, when this Na+ , K+ -ATPase inhibition was quantitated by a colorimetric method that measures ATPase-catalyzed release of inorganic phosphorus, the data obtained were inconsistent and showed great variation. We developed a novel method using inductively coupled plasma mass spectrometry (ICP-MS) to quantitate the amount of intracellular Rb+ . This method largely mimics the 86 RbCl tracer flux assay, but it uses non-radioactive RbCl as a flux substrate. The results demonstrated that this method has better precision and accuracy than the conventional colorimetric method. More importantly, this method is free from radioactive substances, which is expected to make it safer and more convenient than the radioactive 86 RbCl tracer flux method. In conclusion, the ICP-MS method for Na+ , K+ -ATPase activity determination is novel and accurate. It can also provide a reference for studying the transport of other metal ions across membranes under biological conditions.

Surprising Condensation Reactions of the Azadithiolate Cofactor.

Azadithiolate, a cofactor found in all [FeFe]-hydrogenases, is shown to undergo acid-catalyzed rearrangement. Fe2 [(SCH2 )2 NH](CO)6 self-condenses to give Fe6 [(SCH2 )3 N]2 (CO)17 . The reaction, which is driven by loss of NH4+ , illustrates the exchange of the amine group. X-ray crystallography reveals that three Fe2 (SR)2 (CO)x butterfly subunits interconnected by the aminotrithiolate [N(CH2 S)3 ]3- . Mechanistic studies reveal that Fe2 [(SCH2 )2 NR](CO)6 participate in a range of amine exchange reactions, enabling new methodologies for modifying the adt cofactor. Ru2 [(SCH2 )2 NH](CO)6 also rearranges, but proceeds further to give derivatives with Ru-alkyl bonds Ru6 [(SCH2 )3 N][(SCH2 )2 NCH2 ]S(CO)17 and [Ru2 [(SCH2 )2 NCH2 ](CO)5 ]2 S.

Periodic Tendril Perversion and Helices in the AMoO2F3 (A = K, Rb, NH4, Tl) Family.

Although compounds of the formula AMoO2F3 (A = K, Rb, Cs, NH4, Tl) have been known for decades, crystal structures have only been reported for CsMoO2F3 and NH4MoO2F3. The three compounds (Rb/NH4/Tl)MoO2F3 are isostructural and crystallize in the centrosymmetric space group C2/c (No. 15). The compounds contain the MoO2F3- anionic chain, composed of corner-sharing MoO2F4 octahedra, with Mo6+ coordinated by two cis bridging fluoride anions that are trans to terminal oxide anions. The MoO2F3- chain has a very unusual and complex chain structure; a single chain contains alternating zigzag and helical sections. These helical regions alternate in chirality along the chain, and thus the chains exhibit periodic tendril perversion. To the best of the authors' knowledge, no other materials with a similar chain structure have been reported. On the other hand, KMoO2F3 is noncentrosymmetric and chiral, crystallizing in the enantiomorphic space group P212121 (No. 19). KMoO2F3 also contains the MoO2F3- anionic chain. However, the chain is helical, with only one enantiomer present, resulting in a chiral, noncentrosymmetric structure.

Automated dynamic motion correction using normalized gradient fields for 82rubidium PET myocardial blood flow quantification.

BACKGROUND: Patient motion can lead to misalignment of left ventricular (LV) volumes-of-interest (VOIs) and subsequently inaccurate quantification of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to develop an image-based 3D-automated motion-correction algorithm that corrects the full dynamic sequence for translational motion, especially in the early blood phase frames (~ first minute) where the injected tracer activity is transitioning from the blood pool to the myocardium and where conventional image registration algorithms have had limited success. METHODS: We studied 225 consecutive patients who underwent dynamic rest/stress rubidium-82 chloride (82Rb) PET imaging. Dynamic image series consisting of 30 frames were reconstructed with frame durations ranging from 5 to 80 seconds. An automated algorithm localized the RV and LV blood pools in space and time and then registered each frame to a tissue reference image volume using normalized gradient fields with a modification of a signed distance function. The computed shifts and their global and regional flow estimates were compared to those of reference shifts that were assessed by three physician readers. RESULTS: The automated motion-correction shifts were within 5 mm of the manual motion-correction shifts across the entire sequence. The automated and manual motion-correction global MBF values had excellent linear agreement (R = 0.99, y = 0.97x + 0.06). Uncorrected flows outside of the limits of agreement with the manual motion-corrected flows were brought into agreement in 90% of the cases for global MBF and in 87% of the cases for global MFR. The limits of agreement for stress MBF were also reduced twofold globally and by fourfold in the RCA territory. CONCLUSIONS: An image-based, automated motion-correction algorithm for dynamic PET across the entire dynamic sequence using normalized gradient fields matched the results of manual motion correction in reducing bias and variance in MBF and MFR, particularly in the RCA territory.