Isomerization Reactions of the Cu15V+ Cluster: A Density Functional Theory Study.

The investigation of the chemical reactivity of complex systems such as transition metal clusters is a very complicated task because often the structures of the corresponding transition states are far from being intuitive. Bimetallic transition metal clusters represent a particular class of complex systems. In this work, density functional theory (DFT) is applied to study the isomerization reactions of the Cu15V+ cluster. Full geometry optimizations of dozens of initial structures taken along Born-Oppenheimer molecular dynamics (BOMD) trajectories were performed using a quasi-Newton method in a reduced space Cartesian coordinate system that works considering the internal degrees of freedom. Harmonic frequencies calculations were performed at the optimized structures. To study the isomerization reactions between the obtained stable isomers, a hierarchical transition state algorithm has been applied to locate the transition states of this cluster. The found transition states were than connected with the corresponding minimum structures by calculating the intrinsic reaction coordinates. This work demonstrates the capability of the applied method to study non-intuitive rearrangement mechanisms in complex finite systems and to create networks between minima and transition state structures on their potential energy surface.

Simultaneous robotic kidney transplantation and bariatric surgery for morbidly obese patients with end-stage renal failure.

Patients with obesity have limited access to kidney transplantation, mainly due to an increased incidence of surgical complications, which could be reduced with selective use of robotic-assisted surgery. This prospective randomized controlled trial compares the safety and efficacy of combining robotic sleeve gastrectomy and robotic-assisted kidney transplant to robotic kidney transplant alone in candidates with class II or III obesity. Twenty candidates were recruited, 11 were randomized to the robotic sleeve gastrectomy and robotic-assisted kidney transplant group and 9 to the robotic kidney transplant group. At 12-month follow-up, change in body mass index was -8.76 ± 1.82 in the robotic sleeve gastrectomy and robotic-assisted kidney transplant group compared to 1.70 ± 2.30 in the robotic kidney transplant group (P = .0041). Estimated glomerular filtration rate, serum creatinine, readmission rates, and graft failure rates up to 12 months were not different between the two groups. Length of surgery was longer in the robotic sleeve gastrectomy and robotic-assisted kidney transplant group (405 minutes vs. 269 minutes, p = .00304) without increase in estimated blood loss (120 ml vs. 117 ml, p = .908) or incidence of surgical complications. Combined robotic-assisted kidney transplant and sleeve gastrectomy is safe and effective compared to robotic-assisted kidney transplant alone.

Spectral Characteristics Related to Chemical Substructures and Structures Indicative of Organic Precursors from Fulvic Acids in Sediments by NMR and HPLC-ESI-MS.

The aim of this work was to determine Fulvic Acids (FAs) in sediments to better know their composition at the molecular level and to propose substructures and structures of organic precursors. The sediment samples were obtained from a priority area for the conservation of ecosystems and biodiversity in Mexico. FAs were extracted and purified using modifications to the International Humic Substances Society method. The characterization was carried out by 1D and 2D nuclear magnetic resonance (NMR) and high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) in positive (ESI+) and negative (ESI-) modes. Twelve substructures were proposed by the COSY and HSQC experiments, correlating with compounds likely belonging to lignin derivatives obtained from soils as previously reported. The analysis of spectra obtained by HPLC-ESI-MS indicated likely presence of compounds chemically similar to that of the substructures elucidated by NMR. FAs studied are mainly constituted by carboxylic acids, hydroxyl, esters, vinyls, aliphatics, substituted aromatic rings, and amines, presenting structures related to organic precursors, such as lignin derivatives and polysaccharides.

Cardio-oncology: the Nuclear Option.

PURPOSE OF REVIEW: Cardio-oncology focuses increased effort to decrease cancer treatment-related cardiotoxicity while continuing to improve outcomes. We sought to synthesize the latest in nuclear cardiology as it pertains to the assessment of left ventricular function in preventative guidelines and comparison to other modalities, novel molecular markers of pre-clinical cardiotoxicity, and its role in cardiac amyloid diagnosis. RECENT FINDINGS: Planar ERNA (equilibrium radionuclide angiocardiography) provides a reliable and proven means of monitoring and preventing anthracycline cardiotoxicity, and SPECT ERNA using solid-state gamma cameras may provide reproducible assessments of left ventricular function with reduced radiation exposure. While certain chemotherapeutics have vascular side effects, the use of stress perfusion imaging has still not been adequately studied for routine use. Similarly, markers of apoptosis, inflammation, and sympathetic nerve dysfunction are promising, but are still not ready for uniform usage. SPECT tracers can assist in nonbiopsy diagnosis of cardiac amyloid. Nuclear cardiology is a significant contributor to the multimodality approach to cardio-oncology.

2,6-Dihy-droxy-4-oxo-2-(pyridin-1-ium-3-yl)-4H-1,3,2-benzodioxaborinin-2-ide 0.67-hydrate.

The asymmetric unit of the title compound, C12H10BNO5·0.67H2O, contains three independent pyridinylboronic acid esters adopting zwitterionic forms and two water mol-ecules. The six-membered heterocyclic rings in the boronic esters have half-chair conformations and the deviations of the B atoms from the boronate mean planes range from 0.456 (3) to 0.657 (3) Å. All of the B atoms have tetra-hedral coordination environments, with B-O and B-C bond lengths of 1.446 (4)-1.539 (3) and 1.590 (5)-1.609 (5) Å, respectively. In the crystal, the ester and water mol-ecules are linked into a three-dimensional network by a large number of O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds. The crystal packing is further accomplished by π-π inter-actions, with centroid-centroid distances of 3.621 (4)-3.787 (4) Å.

Substituent effects and pH profiles for stability constants of arylboronic acid diol esters.

Stability constants of boronic acid diol esters in aqueous solution have been determined potentiometrically for a series of meta-, para-substituted phenylboronic acids and diols of variable acidity. The constants ß(11-1) for reactions between neutral forms of reactants producing the anionic ester plus proton follow the Hammett equation with ρ depending on pKa of diol and varying from 2.0 for glucose to 1.29 for 4-nitrocatechol. Observed stability constants (K(obs)) measured by UV-vis and fluorometric titrations at variable pH for esters of 4,5-dihydroxy-1,3-benzenedisulfonate (Tiron) generally agree with those expected on the basis of ß(11-1) values, but the direct fitting of K(obs) vs pH profiles gives shifted pKa values both for boronic acids and diol as a result of significant interdependence of fitting parameters. The subsituent effects on absorption and fluorescence spectra of Tiron arylboronate esters are characterized. The K(obs) for Tiron determined by (11)B NMR titrations are approximately 1 order of magnitude smaller than those determined by UV-vis titrations under identical conditions. A general equation, which makes possible an estimate of ß(11-1) for any pair of boronic acid and diol from their pKa values, is proposed on the basis of established Brönsted-type correlation of Hammett parameters for ß(11-1) with acidity of diols. The equation allows one to calculate stability constants expected only on basis of acid-base properties of the components, thus permitting more strict evaluation of contributions of additional factors such as steric or charge effects to the ester stability.

Competing risks for death and cardiac transplantation in children with dilated cardiomyopathy: results from the pediatric cardiomyopathy registry.

BACKGROUND: Pediatric dilated cardiomyopathy (DCM) is the leading indication for heart transplantation after 1 year of age. Risk factors by etiology at clinical presentation have not been determined separately for death and transplantation in population-based studies. Competing risks analysis may inform patient prioritization for transplantation listing. METHODS AND RESULTS: The Pediatric Cardiomyopathy Registry enrolled 1731 children diagnosed with DCM from 1990 to 2007. Etiologic, demographic, and echocardiographic data collected at diagnosis were analyzed with competing risks methods stratified by DCM etiology to identify predictors of death and transplantation. For idiopathic DCM (n=1192), diagnosis after 6 years of age, congestive heart failure, and lower left ventricular (LV) fractional shortening z score were independently associated with both death and transplantation equally. In contrast, increased LV end-diastolic dimension z score was associated only with transplantation, whereas lower height-for-age z score was associated only with death. For neuromuscular disease (n=139), lower LV fractional shortening was associated equally with both end points, but increased LV end-diastolic dimension was associated only with transplantation. The risks of death and transplantation were increased equally for older age at diagnosis, congestive heart failure, and increased LV end-diastolic dimension among those with myocarditis (n=272) and for congestive heart failure and decreased LV fractional shortening among those with familial DCM (n=79). CONCLUSIONS: Risk factors for death and transplantation in children varied by DCM etiology. For idiopathic DCM, increased LV end-diastolic dimension was associated with increased transplantation risk but not mortality. Conversely, short stature was significantly related to death but not transplantation. These findings may present an opportunity to improve the transplantation selection algorithm.

4-[(E)-2-(Pyridin-2-yl)ethen-yl]pyridine-terephthalic acid (2/1).

The title 2:1 co-crystal, 2C12H10N2·C8H6O4, crystallizes with one mol-ecule of 4-[(E)-2-(pyridin-2-yl)ethen-yl]pyridine (A) and one half-mol-ecule of terephthalic acid (B) in the asymmetric unit. In the crystal, the components are linked through heterodimeric COOH⋯Npyridine synthons, forming linear aggregates of composition -A-B-A-B-. Further linkage through weak C-H⋯O and C-H⋯π inter-actions gives two-dimensional hydrogen-bonded undulating sheets propagating in the [100] and [010] directions. These layers are connected through additional weak C-H⋯O contacts, forming a three-dimensional structure.

Temporary Deceased Donor Splenic Transplant Prior to Intestinal Transplantation: A New Strategy for Desensitization?

Intestinal transplantation is a therapeutic treatment option for patients with irreversible intestinal failure. The presence of donor-specific antibodies (DSAs) has been associated with increased antibody-mediated rejection and allograft loss for recipients of all the solid organ transplants. This case report describes the posttransplant course in the first year of a patient who received a T-cell and B-cell flow cross-match (FXM) and complement-dependent cytotoxicity cross-match positive intestinal transplant in the presence of several class I and class II DSAs who underwent a "temporary desensitization" using the donor spleen. The temporary donor splenic transplant removed several class I and II DSAs as demonstrated by the negative subsequent T-cell FXM, the decreased mean channel shift of the positive B-cell FXM with a significant decrease in DSA mean florescence intensity post temporary splenic transplant. The patient experienced an isolated incidence of acute rejection, which responded to therapy. He had no infectious or cancerous sequelae from the immunosuppression modalities. He was able to discontinue total parenteral nutrition and gained weight after the procedure. Long-term effects are not able to be determined from this approach; hence, further research is warranted to better evaluate the real efficacy of this strategy.

Tracheostomy Following Liver Transplantation.

BACKGROUND: With increased demand for liver transplantation, sicker patients are being transplanted frequently. These patients are at a higher risk of significant postoperative morbidity, including respiratory failure. This study evaluated the phenotype that characterizes liver transplant candidates who may benefit from early tracheostomy. METHODS: A single center retrospective review of all liver transplant candidates between January 2012 and December 2017. Patients who eventually required tracheostomies were identified and compared to their counterparts. RESULTS: Of the 130 liver transplants performed during the study period, 11 patients required tracheostomy. Although patients in the tracheostomized population (TP) did not have significantly worse preoperative functional status (<4 metabolic equivalents; 64% vs 42%, P = .21), they had a higher native model for end-stage liver disease (MELD) score (37 vs 30, P < .05) at the time of transplantation. Patients who eventually succumbed to respiratory failure had lower arterial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratios at the start of surgery and remained unchanged for the duration of surgery compared with the nontracheostomy group (P < .05). TP patients required more net fluid intraoperatively (7.3 vs 5.0 L, P < .05), increased length of time to attempted extubation (3.5 vs 1 day, P < .05), longer ventilation days (15 vs 1 day, P < .05), increased length of stay (37 vs 9 days, P < .05), and higher 1-year mortality (36% vs 8%, P < .05). CONCLUSIONS: Based on our findings, patients with a high MELD score (>30), net postoperative fluid balance >6 L, and PaO2/FiO2 ratio ≤300 who fail to wean off mechanical ventilation after 72 hours may benefit from tracheostomy during the postoperative period.

Macrocyclic diorganotin complexes of gamma-amino acid dithiocarbamates as hosts for ion-pair recognition.

The dimethyl-, di-n-butyl-, and diphenyltin(IV) dithiocarbamate (dtc) complexes [{R2Sn(L-dtc)}x] 1-7 (1, L = L1, R = Me; 2, L = L1, R = n-Bu; 3, L = L2, R = Me, x = infinity; 4, L = L2, R = n-Bu; 5, L = L3, R = Me, x = 2; 6, L = L3, R = n-Bu, x = 2; 7, L = L3, R = Ph, x = 2) have been prepared from a series of secondary amino acid (AA) homologues as starting materials: N-benzylglycine (alpha-AA derivative = L1), N-benzyl-3-aminopropionic acid (beta-AA derivative = L2), and N-benzyl-4-aminobutyric acid (gamma-AA derivative = L3). The resulting compounds have been characterized by elemental analysis, mass spectrometry, IR and NMR ((1)H, (13)C, and (119)Sn) spectroscopy, thermogravimetric analysis, and X-ray crystallography, showing that in all complexes both functional groups of the heteroleptic ligands are coordinated to the tin atoms. By X-ray diffraction analysis, it could be shown that [{Me2Sn(L2-dtc)}x] (3) is polymeric in the solid state, while the complexes derived from L3 (5-7) have dinuclear 18-membered macrocyclic structures of the composition [{R2Sn(L3-dtc)}2]. For the remaining compounds, it could not be established with certainty whether the structures are macrocyclic or polymeric. A theoretical investigation at the B3LYP/SBKJC(d,p) level of theory indicated that the alpha-AA-dtc complexes might have trinuclear macrocyclic structures. The macrocyclic complexes 5-7 have a double-calix-shaped conformation with two cavities large enough for the inclusion of aliphatic and aromatic guest molecules. They are self-complementary for the formation of supramolecuar synthons that give rise to 1D molecular arrangements in the solid state. Preliminary recognition experiments with tetrabutylammonium acetate have shown that the [{R2Sn(L3-dtc)}2] macrocycles 6 and 7 might interact simultaneously with anions (AcO(-)), which coordinate to the tin atoms, and organic cations (TBA(+)), which accommodate within the hydrophobic cavity (ion-pair recognition).

Pediatric Cardiomyopathy as a Chronic Disease: A Perspective on Comprehensive Care Programs.

Substantial numbers of children with cardiomyopathy are now surviving into adulthood, making it essentially a chronic disease. As a chronic condition, it may be best treated through comprehensive, multidisciplinary treatment programs. Such programs have improved health outcomes and reduced costs in managing other pediatric chronic diseases and heart failure in adults, but the treatment and cost implications of programs for managing pediatric cardiomyopathy are unknown. We investigated the treatment and cost implications of establishing such programs by reviewing cost-effectiveness studies of similar programs, estimating the current inpatient costs of this diagnosis, and interviewing experts in the field about the need and desirability of these programs. According to our findings, comprehensive pediatric heart failure programs do exist, but they have not been evaluated or even described in the literature. Consensus among experts in the field is that such programs are highly desirable, and similar programs have reported tremendous cost savings through early and intensive management: the return on investment has been as high as 22 to 1. Another study reported that mean length of stay decreased from 83.9 to 10.6 days, mean annual admissions decreased from 2,796 to 1,622, and median hospital charges decreased from $26.1 million to $14.6 million. In conclusion, limited experience and strong circumstantial evidence suggest that, despite substantial costs, comprehensive multidisciplinary pediatric heart failure programs would be highly cost-effective and beneficial to patients, families, and institutions alike.

The Pediatric Cardiomyopathy Registry: 1995-2007.

Cardiomyopathy is a serious disorder of the heart muscle and, although rare, it is potentially devastating in children. Funded by the National Heart Lung and Blood Institute since 1994, the Pediatric Cardiomyopathy Registry (PCMR) was designed to describe the epidemiology and clinical course of selected CMs in patients 18 years old or younger and to promote the development of etiology-specific prevention and treatment strategies. Currently, data from more than 3,000 children with cardiomyopathy have been entered in the PCMR database with annual follow-up continuing until death, heart transplant, or loss-to-follow up. Using PCMR data, the incidence of cardiomyopathy in two large regions of the United States is estimated to be 1.13 cases per 100,000 children. Only 1/3 of children had a known etiology at the time of cardiomyopathy diagnosis. Diagnosis was associated with certain patient characteristics, family history, echocardiographic findings, laboratory testing, and biopsy. Greater incidence was found in boys and infants (<1 yr) for both dilated and hypertrophic cardiomyopathy (DCM, HCM) and black race for only DCM. In DCM, prognosis is worse in older children (>1yr), heart failure (HF) at diagnosis or idiopathic etiology. For HCM, worse prognosis is associated with inborn errors of metabolism or combination of HCM and another cardiomyopathy functional type. The best outcomes were observed in children presenting at age >1 yr with idiopathic HCM. PCMR data have enabled analysis of patients with cardiomyopathy and muscular dystrophy, as well as Noonan Syndrome. Currently, collaborations with the Pediatric Heart Transplant Study group and a newly established Pediatric Cardiomyopathy Biologic Specimen Repository at Texas Children's Hospital will continue to yield important results. The PCMR is the largest and most complete multi-center prospective data resource regarding the etiology, clinical course and outcomes for children with cardiomyopathy.

Supramolecular arrangement and photophysical properties of a dinuclear cyanophenylboronic acid ester.

Boronic esters are useful building blocks for crystal engineering and the generation of supramolecular architectures, including macrocycles, cages and polymers (one-, two- and three-dimensional), with potential utility in diverse fields such as separation, storage and luminescent materials. The novel dinuclear cyanophenylboronic ester described herein, namely 4,4'-(2,4,8,10-tetraoxa-3,9-diboraspiro[5.5]undecane-3,9-diyl)dibenzonitrile, C19H16B2N2O4, was prepared by condensation of 4-cyanophenylboronic acid and pentaerythritol and fully characterized by elemental analysis, IR and NMR (1H and 11B) spectroscopy, single-crystal X-ray diffraction analysis and TG-DSC (thermogravimetry-differential scanning calorimetry) studies. In addition, the photophysical properties were examined in solution and in the solid state by UV-Vis and fluorescence spectroscopies. Density functional theory (DFT) calculations with ethanol as solvent reproduced reasonably well the HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) of the title compound. Hirshfeld surface and fingerprint plot analyses are presented to illustrate the supramolecular connectivity in the solid state.

Outcome Predictors for Pediatric Dilated Cardiomyopathy: A Systematic Review.

Dilated cardiomyopathy comprises the largest group of pediatric cardiomyopathy functional types and is the most common indication for heart transplant in children over 5 years old. Prognostic factors for this condition have long been sought by many researchers. In a systematic review of these factors, we found 32 relevant articles published since 1976. Four studies report finding no predictive factors. In the remaining 28 studies, several factors indicating better prognosis stand out across multiple articles: younger age at diagnosis, higher left-ventricular fractional shortening and ejection fraction, and the presence of myocarditis. Results for other factors conflict across studies: severe mitral regurgitation, arrhythmias, and a family history of cardiomyopathy. Elevated left-ventricular end diastolic pressure was statistically significant in two studies, but it may be of limited utility as a result of its invasiveness. Although most children have congestive heart failure at presentation, only two studies found it to be a significant predictor of mortality. The largest study of this factor qualified the increased risk to 1 year after presentation. Other significant predictors that have not been analyzed or reported by more than one study group, are right ventricular failure and impaired cardiac adrenergic innervation, as detected by radiolabeled meta-iodobenzylguanidine imaging. Although 1- and 5-year survival rates have steadily improved, as more children with DCM receive cardiac transplants, event-free survival rates (the absence of "heart death" resulting in death or transplant) are similar to those from decades ago. A unified risk algorithm may assist in clinical decision-making but requires more studies. Other studies are needed to assess the post-transplant survival experience.

The Apical Localization of Na+, K+-ATPase in Cultured Human Retinal Pigment Epithelial Cells Depends on Expression of the ß2 Subunit.

Na+, K+-ATPase, or the Na+ pump, is a key component in the maintenance of the epithelial phenotype. In most epithelia, the pump is located in the basolateral domain. Studies from our laboratory have shown that the ß1 subunit of Na+, K+-ATPase plays an important role in this mechanism because homotypic ß1-ß1 interactions between neighboring cells stabilize the pump in the lateral membrane. However, in the retinal pigment epithelium (RPE), the Na+ pump is located in the apical domain. The mechanism of polarization in this epithelium is unclear. We hypothesized that the apical polarization of the pump in RPE cells depends on the expression of its ß2 subunit. ARPE-19 cells cultured for up to 8 weeks on inserts did not polarize, and Na+, K+-ATPase was expressed in the basolateral membrane. In the presence of insulin, transferrin and selenic acid (ITS), ARPE-19 cells cultured for 4 weeks acquired an RPE phenotype, and the Na+ pump was visible in the apical domain. Under these conditions, Western blot analysis was employed to detect the ß2 isoform and immunofluorescence analysis revealed an apparent apical distribution of the ß2 subunit. qPCR results showed a time-dependent increase in the level of ß2 isoform mRNA, suggesting regulation at the transcriptional level. Moreover, silencing the expression of the ß2 isoform in ARPE-19 cells resulted in a decrease in the apical localization of the pump, as assessed by the mislocalization of the α2 subunit in that domain. Our results demonstrate that the apical polarization of Na+, K+-ATPase in RPE cells depends on the expression of the ß2 subunit.

Enhanced left ventricular systolic function early in type 2 diabetic mice: clinical implications.

It is unclear whether the increase in availability of substrates for energy production in diabetes can lead to enhanced systolic function early in the disease, before the onset of structural changes to the myocardium. To examine this issue, BKS.Cg-m +/+ Lepr db (db/db) mice with type 2 diabetes and wild type controls had left ventricular pressure-volume relationships determined in situ. We demonstrated that the db/db mice, when compared to their wild type controls, generated greater left ventricular pressure and an enhancement of left ventricular systolic function based on enhanced power/EDV, positive dP/dt, preload recruitable stroke work, dP/dt--EDV relationship, and curvilinear end-systolic elastance. This enhancement in systolic function occurred despite the db/db mice having greater body weight, but similar preload (end-diastolic volume) and afterload (effective arterial elastance). We postulate that the previously described enhancement in renal glomerular filtration rate seen early in type 2 diabetes may be in part due to enhanced left ventricular systolic function early in this disease.

Dynamic profiles of interleukin-6 and the soluble form of CD25 in burned patients.

Changes in the time courses of serum levels of interleukin-6 (IL6) and the soluble form of CD25 (sCD25) were evaluated in 48 burned patients (31 had sepsis, 21 died). Differences among groups along the time were assessed with ANOVA. The Pearson's r correlation coefficient was used to relate quantitative variables. ROC curves were constructed to analyse the prognostic value of IL6 and sCD25. The values of IL6 and sCD25 were related to treatment outcome and time post-burn. In general, two patterns emerged: In non-survivors, there was a depression of sCD25 with time, and an increase in IL6 levels previous to death, whereas survivors had the opposite pattern. On admission, patients with higher levels of sCD25 had a bad prognosis.

[Expanded pedicled forearm flap for reconstruction of multiple finger amputations]. / Expandierter gestielter Unterarmlappen zur Rekonstruktion von multiplen Fingeramputationen.

Soft-tissue injuries of the hand frequently require flap coverage to preserve structures damaged at the time of injury or to facilitate later reconstruction. The radial forearm flap makes local tissue readily available and offers a simple method of reconstruction. Secondary augmentation of the skin flap by means of tissue expansion appears to be a useful alternative to improve the possibilities of reconstruction. This case report describes a primary reconstruction of a hand with multiple finger amputations using both techniques: Forearm flap and tissue expansion.