Dilated ascending aorta is associated with the difficulty in correct placement of pulmonary artery catheter

The present case report highlights that a tense mega-sized aortic root and ascending aorta can mechanically resist the passage of fully inflated (1.5 ml air) balloon to wedge-trace position in the pulmonary artery. Any attempt to push the catheter rather predisposed its recoiling and rebutting into the right ventricle and the cardiac arrhythmia. Inflating continuous cardiac output catheter balloon with lesser volume of air (1 ml) is suggested to overcome this problem.     

Wilson's disease presenting as isolated obsessive-compulsive disorder

Wilson's disease (WD) is a genetic neurodegenerative disorder; it exhibits wide heterogeneity in symptoms and usually presents with liver disease and/ or neuropsychiatric manifestations. The common neurological manifestations observed are dysarthria, gait disturbance, dystonia, rigidity, tremor, dysphagia and chorea. The frequent psychiatric manifestations reported are personality and mood changes, depression, phobias, cognitive impairment, psychosis, anxiety, compulsive and impulsive behavior. Isolated obsessive-compulsive disorder (OCD) is a rare presentation of WD. Reported herein is a case of a 17-year-old boy with isolated OCD. He presented to the psychiatrist with symptoms of contamination obsessions and washing compulsions, along with compulsion of repeated feet tapping and was treated with adequate doses of fluoxetine for 6 months but did not improve. Later on, he was diagnosed as a case of WD and showed improvement with chelating and behavior therapy. This implies the importance of the occurrence of isolated psychological symptoms in WD.     

Depression-free day to utility-weighted score: is it valid?

BACKGROUND: Cost-utility analyses using formulas to convert depression-free days (DFDs) to utility-weighted scores are increasingly common. These formulas are based on linear extrapolation of data documenting the correlation between depression symptom severity and generic health-related quality of life. OBJECTIVE: We sought to examine the validity of formulas converting DFDs to utility weights. METHODS: We undertook an observational study with data collection at baseline, 1 week and 1, 3, 6, 9, and 12 months on 77 subjects (42 inpatient, 35 outpatient) diagnosed with current major depression. Subjects were divided into treatment response categories based on changes in depression severity. Depression severity measures used were the Hamilton Rating Scale for Depression (HAM-17) and Beck Depression Inventory (BDI) and the health-related quality of life measure was the self-administered Quality of Well-Being scale (QWB-SA). DFD calculations were based on depression severity scores and converted to utility weights using available formulas. Utility-weighted data collected over the course of 1 year were used to estimate quality-adjusted life years (QALYs). RESULTS: QALYs estimated from the QWB-SA were significantly lower than those based on utility-weighted DFD calculations but the incremental QALYs were not significantly different. Using a slightly lower utility-weighted conversion factor for the BDI or a larger BDI severity range to calculate DFDs resulted in a better fit compared with the QWB-SA. CONCLUSIONS: Our results support the validity of the existing HAM-17 utility-weighted formula and suggest modifications for the BDI formula. If generic health-related quality of life measures are not available for conducting cost-utility analyses of depression interventions then the existing HAM-17 and modified BDI formulas appear to be reasonable alternatives.     

Individual Differences in Attentional Bias Associated with Cocaine Dependence Are Related to Varying Engagement of Neural Processing Networks

Cocaine and other drug dependencies are associated with significant attentional bias for drug use stimuli that represents a candidate cognitive marker of drug dependence and treatment outcomes. We explored, using fMRI, the role of discrete neural processing networks in the representation of individual differences in the drug attentional bias effect associated with cocaine dependence (AB-coc) using a word counting Stroop task with personalized cocaine use stimuli (cocStroop). The cocStroop behavioral and neural responses were further compared with those associated with a negative emotional word Stroop task (eStroop) and a neutral word counting Stroop task (cStroop). Brain–behavior correlations were explored using both network-level correlation analysis following independent component analysis (ICA) and voxel-level, brain-wide univariate correlation analysis. Variation in the attentional bias effect for cocaine use stimuli among cocaine-dependent men and women was related to the recruitment of two separate neural processing networks related to stimulus attention and salience attribution (inferior frontal–parietal–ventral insula), and the processing of the negative affective properties of cocaine stimuli (frontal–temporal–cingulate). Recruitment of a sensory–motor–dorsal insula network was negatively correlated with AB-coc and suggested a regulatory role related to the sensorimotor processing of cocaine stimuli. The attentional bias effect for cocaine stimuli and for negative affective word stimuli were significantly correlated across individuals, and both were correlated with the activity of the frontal–temporal–cingulate network. Functional connectivity for a single prefrontal–striatal–occipital network correlated with variation in general cognitive control (cStroop) that was unrelated to behavioral or neural network correlates of cocStroop- or eStroop-related attentional bias. A brain-wide mass univariate analysis demonstrated the significant correlation of individual attentional bias effect for cocaine stimuli with distributed activations in the frontal, occipitotemporal, parietal, cingulate, and premotor cortex. These findings support the involvement of multiple processes and brain networks in mediating individual differences in risk for relapse associated with drug dependence.     

Metal free oxidation of vinamidine derivatives: a simple synthesis of α-keto-β-diimine ligands

Oxidation of vinamidinium salts with meta-chloroperbenzoic acid is the key synthetic step towards new persistent 1,3-di(amino)oxyallyl radical cations. When applied to parent vinamidines, this protocol allows for a simple straightforward synthesis of α-keto-β-diimine ligands, for which no convenient synthesis was previously available.

Oxidation of vinamidinium salts with meta-chloroperbenzoic acid not only provides access to new persistent 1,3-di(amino)oxyallyl radical cations, but also to α-keto-β-diimine ligands, for which no convenient synthesis was previously available.

β-Diketiminates, so-called NacNac ligands (Scheme 1), have been a focus in coordination chemistry for decades.¹ Structural modifications include a large variety of N-substituents, as well as bulky,² electron-withdrawing,³ or electron donating⁴ R groups. Substitution at the central carbon atom (R′ ≠ H) has also been explored as a strategy to tame this reactive position and enhance the chemical stability of the complex.⁵ The α-keto-β-diimines are among rare representatives with a more significant modification at the central carbon. These electron-deficient ligands have found applications in the design of highly active nickel(ii) initiators for the synthesis of high molecular weight polyethylenes and poly-α-olefins.⁶ Interestingly, low-disperse semi-crystalline polymers could be obtained under living conditions and remarkable enantiomorphic site control could be achieved.⁷Open in a separate windowScheme 1Previously reported synthesis of α-keto-β-diimines and synthesis of air-persistent radical 4˙⁺ from vinamidinium 3.The low availability of α-keto-β-diimines has clearly hampered further development. Their metal complexes have been known for long, but only as occasional by-products from the air-decomposition of unprotected NacNac complexes (R′ = H).⁸ To date only a rare selective oxygen-degradation of copper(ii) complexes allows for the synthesis of a handful of 2,4-di(arylimino)pentan-3-ones 2 from the corresponding vinamidines 1.^6a,d,9 The procedure requires (i) the synthesis of the NacNac–Cu(ii) complex, (ii) oxidation at the ligand with dioxygen in a methanol/dichloromethane mixture, (iii) the decomplexation and hydrolysis of the resulting hemiacetal ligand (Scheme 1). In turn, we had to synthesize 2,4-bis((2,6-diisopropylphenyl)imino)pentan-3-one 2a and experienced firsthand the length and limitations of this methodology. Among the three steps, the oxidation of the NacNac–copper complex is especially inconvenient and wasteful, as it consists of a continuous bubbling of pure dioxygen in a warm solution for two days.^6a Recently, we released a parented, though in principle far simpler, oxidation of tetrakis(dimethylamino) vinamidinium 3 into di(amidinium)ketone 4²⁺ with meta-chloroperbenzoic acid (m-CPBA) as oxidant. Our initial focus was on the corresponding radical 4˙⁺, which was found remarkably air-persistent, despite minimal steric hindrance.¹⁰ Herein we report how further assessment of such 1,3-(diamino)oxyallyl radical cations ultimately led to a straightforward protocole for the synthesis of α-keto-β-diimines from NacNac precursors.Prior to 4˙⁺, only two oxyallyl radical cations had been synthesized from the reaction of rare stable electrophilic carbenes with carbon monoxide.^11–13 In principle, the oxidation of vinamidinium salts should provide for a more simple and general route, with no need of sophisticated N-substituents. To probe this assumption, we first considered the oxidative functionalization of the chloride salt of vinamidinium 5⁺, which was synthesized from N,N-dimethyl-benzamide and 1-dimethylamino-1-phenylethene.¹⁴ Addition of m-CPBA at room temperature yielded 2-chlorovinamidium 6 in 71% yield (Scheme 2). This result indicated the competitive formation of meta-chlorobenzoyl hypochlorite Cl(C₆H₄)CO₂Cl, from the reaction of chloride anions with m-CPBA.¹⁵ Therefore we proceeded to an anion metathesis. The resulting tetrafluoroborate salt reacted with m-CPBA, but this time to afford 7·H⁺, which was fully characterized and isolated in 74% yield. Of note, the NMR spectra of vinamidiniums 6 and 7·H⁺ mostly differ in the ¹³C chemical shift of their central carbon: 94 and 127 ppm, respectively. They were unambiguously characterized by mass spectrometry analyses and X-ray diffraction studies (Fig. 1).Open in a separate windowScheme 2Redox transformations of di(imidazole)methane and 1,3-di(phenyl) vinamidinium derivatives.Open in a separate windowFig. 1X-ray structures of 6, 7·H⁺ and 2c,d with thermal ellipsoids drawn at 50% probability level. Most hydrogen atoms, solvent molecules and counter-anions were omitted for clarity.Solutions of 7·H⁺ featured an EPR signal upon exposure to air. This slow reaction could be brought to fast completion in presence of potassium hydrogenocarbonate. The remarkable persistency under aerobic conditions of the resulting radical (in aerated solutions for several hours) was reminiscent of our previously reported stable oxyallyl radicals, some being similarly synthesized by auto-oxidation of parented enol-cations.^11a Therefore, we hypothesized the formation of radical 7˙⁺. Although the radical ultimately decayed and couldn''t be isolated, the excellent fit between the experimental EPR hyperfine coupling constants¹⁶ and the calculated values¹⁷ for 7˙⁺ strongly supported this reasonable assumption (Fig. 2a). The reaction of 7·H⁺ with excess meta-chloroperbenzoic acid or stronger oxidants, such dibromine or potassium ferricyanate, led to over oxidation and directly afforded EPR-silent mixtures of trione 8 and the corresponding hydrated gem-diol 8·H₂O,¹⁸ likely through the formation and subsequent hydrolysis of electron-poor di(iminium)ketone 7²⁺.Open in a separate windowFig. 2Experimental isotropic X-band EPR spectra in dichloromethane at room temperature (plain black line) of 7˙⁺ (a), 10˙⁺ (b) and a crude reaction mixture of m-CPBA and 1a (c). Simulated spectra (dashed blue line) were obtained with (a) a Lorentzian line-broadening parameter of 0.22 and the following set of hyperfine constants: a(¹⁴N) = 8.6 MHz (2 nuclei) and a(¹H) = 12.0 MHz (12 nuclei); (b) with a Lorentzian line-broadening parameter of 0.013 and the following set of hyperfine constants: a(¹⁴N) = 3.1 MHz (4 nuclei), a(¹H) = 6.5 MHz (12 nuclei) and a(¹H) = 0.86 MHz (4 nuclei); (c) with a Lorentzian line-broadening parameter of 0.37 and the following set of hyperfine constants: a(¹⁴N) = 7.8 MHz (2 nuclei), a(¹H) = 16.5 MHz (1 nucleus) and a(¹H) = 15.6 MHz (6 nuclei).We turned to mono(methine)cyanine 9 featuring electron-richer benzimidazole patterns.¹⁹ However, the reaction of 9 with m-CPBA afforded known²⁰ 1,3-dimethyl- benzimidazolium 10, and not the expected di(benzimidazolium)ketone 13²⁺ (Scheme 2). Note that uncompleted, but clean, formation of 10 was still observed when adding sub-stoichiometric (one equivalent) m-CPBA over one hour at −78 °C. Importantly, dication 13²⁺ could be finally synthesized by the oxidation of di(imine)methane 11¹⁹ by m-CPBA, followed by di(alkylation) of the resulting di(imine)ketone 12. Given that 13²⁺ was found almost unreactive towards water, the formation of 10 from 9 results from further oxidative cleavages of 13²⁺, and not its hydrolysis.²¹ According to cyclic voltammetry experiments, 13²⁺ undergoes successive reductions at E_1/2 = −0.12 V vs. Fc/Fc⁺ (reversible) and E_pc = −0.9 V (with further chemical evolution), which we attributed to the formation of radical cation 13˙⁺ and zwitterionic oxyallyl 13, respectively (see ESI^†). We performed the electrochemical reduction of a solution of 13²⁺ in acetonitrile at E = −0.5 V. The stoichiometry (one coulomb per mole of substrate), the observation of a strong EPR signal, as well as an excellent fit between experimental and theoretical hyperfine coupling constants, confirmed the formation of persistent 13˙⁺ (Fig. 2b), which ultimately decayed at room temperature after several hours.The formation of di(imine)ketone 12 from 11 was so clean that it prompted us to explore further the direct oxidation of NacNac precursors. To our delight, treatment of 1a²² afforded 2a in 98% yield. In contrast with the former long and tedious syntheses from literature, the one-step reaction was completed after one hour at room temperature on multigram scales. EPR monitoring of the reaction showed the formation of a paramagnetic intermediate. Simulation of the hyperfine structure of the spectra required significant coupling with a single proton, in addition to two equivalent nitrogen atoms and six protons (Fig. 2c). This suggested the transient formation of N-protonated radical 1a·H˙⁺, parented to 4˙⁺, 7˙⁺ and 13˙⁺, thus implying closely related pathways for the m-CPBA oxidation of vinamidiniums and vinamidine 1a.The only few reported β-di(imine)ketones were derivatives of acetylacetone and ortho-substituted anilines. Apart from 1a, which can be stored for several days, they were described as unstable ligands, to be used as soon as synthesized.^6d We applied our protocole to vinamidine 1b²¹ with 2,4,6-trimethylaryl N-substituents and, indeed, the resulting ketone 2b decayed into a complex mixture within hours. Fast work-up allowed for its isolation in 75% yield (Scheme 3). However, even freshly crystalized 2b contained an impurity with similar NMR chemical shifts, except for a ¹³C NMR signal (quarternary carbon) at 94 ppm in place of the CO band of 2b at 194 ppm. Although the instability of 2b limited further investigations, drying crystals in vacuo in presence of P₂O₅ decreased the amount of impurity, allowing us to assign this latter to the corresponding hydrated gem-diol 2b·H₂0.^23,24Open in a separate windowScheme 3One-step synthesis of α-keto-β-diimines 2a–d from vinamidines 1a–d.Finally, we considered vinamidines 1c²⁵ and 1d,^4b,d with phenyl and di(methyl)amino R groups, respectively. The corresponding di(imine)ketones 2c,d, which are out of reach of previous methods, were isolated in 86–87% yield. They features similar key structural data (IR_ATR: ν = 1700 cm⁻¹; ¹³C NMR δ_CO = 194–191 ppm). Their structures were asserted by a structural X-ray diffraction study (Fig. 1). Importantly, in ketones 2c,d were found remarkably bench stable and have been stored for month with no noticeable degradation.In conclusion, the synthesis and characterization of radicals 7˙⁺ and 13˙⁺ are further evidences that introducing 1,3-di(amino)oxyallyl patterns is a robust principle for the design of persistent radical cations. However, the outcome of the reaction of vinamidiniums with m-CPBA is too dependent of the substitution pattern to constitute a general route and over-oxidation is only manageable with extra electron-donating amino groups. In contrast, when applied to vinamidines, this protocol allows for a straightforward synthesis of α-keto-β-diimines. In addition to its simplicity, stable derivatives were isolated, with unprecedented bulky or electron-donating R groups. We are now evaluating these new ligands for nickel-initiated polymerization of ethylene.