A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur.

Isothiocyanates (ITCs) are typically prepared using amines and highly toxic reagents such as thiophosgene, its derivatives, or CS2. In this work, an investigation of a multicomponent reaction (MCR) using isocyanides, elemental sulfur and amines revealed that isocyanides can be converted to isothiocyanates using sulfur and catalytic amounts of amine bases, especially DBU (down to 2 mol%). This new catalytic reaction was optimized in terms of sustainability, especially considering benign solvents such as Cyrene™ or γ-butyrolactone (GBL) under moderate heating (40 °C). Purification by column chromatography was further optimized to generate less waste by maintaining high purity of the product. Thus, E-factors as low as 0.989 were achieved and the versatility of this straightforward procedure was shown by converting 20 different isocyanides under catalytic conditions, while obtaining moderate to high yields (34-95%).

Sustainable catalytic rearrangement of terpene-derived epoxides: towards bio-based biscarbonyl monomers.

Seeking a sustainable and selective approach for terpene modification, a catalyst deconvolution approach was applied to the Meinwald rearrangement of (+)-limonene oxide as a model substrate to yield dihydrocarvone. In order to identify the most suitable catalyst and reaction conditions, different Lewis acids were evaluated. Bismuth triflate proved to be the most active catalyst under mild reaction conditions, with a low catalyst loading (1 mol%) and a relatively short reaction time (3 h). The optimized reaction conditions were subsequently transferred to other terpene-based epoxides, yielding different bio-based biscarbonyl structures, which constitute interesting and valuable substances, e.g. for polymer synthesis or as fragrances. Monoepoxides derived from (R)-(-)-carvone and (+)-dihydrocarvone rearranged to the desired products with high selectivities and yields. γ-Terpinene dioxide could be transformed in a double rearrangement to the respective biscarbonyl in moderate yields. A better result was achieved for limonene dioxide after further adjustment of the protocol to reach acceptable yields with a low catalyst loading of 0.1 mol% using 2-methyl tetrahydrofuran as a sustainable solvent. Compared to many procedures described in the literature, this procedure represents a step towards an increased sustainability in terpene modification by considering several principles of Green Chemistry, such as renewable resources, catalysis and mild reaction conditions for elementary chemical transformations. This article is part of a discussion meeting issue 'Science to enable the circular economy'.

Percutaneous Microwave Ablation of Histologically Proven T1 Renal Cell Carcinoma.

OBJECTIVES: To assess the safety and efficacy of percutaneous microwave ablation (MWA) of histologically proven T1 renal cell carcinoma (RCC). METHODS: We analysed patients with a histologically proven RCC (≤ 7 cm) treated by MWA from April 2012-April 2018. Primary and secondary efficacy, local tumour recurrence (LTR), morbidity and mortality were reported. Efficacy was defined as no residual tumour enhancement on follow-up imaging 1 month after the first ablation (primary efficacy) and after re-ablation(s) for residual disease (secondary efficacy). Adverse events (AE) were registered by the Clavien-Dindo classification and the common terminology criteria for AE. Univariable and multivariable logistic regression analyses were performed to investigate a relation among pre-treatment factors incomplete ablation and complications. RESULTS: In 100 patients, a total of 108 RCCs (85 T1a and 23 T1b) were treated by MWA. Median size was 3.2 cm (IQR 2.4-4.0). Primary efficacy was 89% (95%CI 0.81-0.94) for T1a lesions and 52% (95%CI 0.31-0.73) for T1b lesions (p < 0.001). Fifteen lesions (7 T1a) were re-ablated for residual disease by MWA in one (n = 13) and two (n = 2, both T1b) sessions resulting in secondary efficacy rates of 99% (T1a) and 95% (T1b, p = 0.352). LTR occurred in four tumours (2 T1a, 2 T1b) after 10-60 months. Six (4%) AEs grade > 3-5 were observed (2 T1a, 4 T1b, p = 0.045). Multivariable analysis showed that mR.E.N.A.L. nephrometry was independently associated with incomplete ablation (p = 0.012). CONCLUSION: Microwave ablation is safe and effective for T1a and T1b RCC lesions with a significantly lower primary efficacy for T1b lesions.

The hidden simplicity of subduction megathrust earthquakes.

The largest observed earthquakes occur on subduction interfaces and frequently cause widespread damage and loss of life. Understanding the rupture behavior of megathrust events is crucial for earthquake rupture physics, as well as for earthquake early-warning systems. However, the large variability in behavior between individual events seemingly defies a description with a simple unifying model. Here we use three source time function (STF) data sets for subduction zone earthquakes, with moment magnitude Mw ≥ 7, and show that such large ruptures share a typical universal behavior. The median STF is scalable between events with different sizes, grows linearly, and is nearly triangular. The deviations from the median behavior are multiplicative and Gaussian-that is, they are proportionally larger for larger events. Our observations suggest that earthquake magnitudes cannot be predicted from the characteristics of rupture onsets.

Peptide array functionalization via the Ugi four-component reaction.

The Ugi four-component reaction was investigated as a tool for the functionalization of peptide arrays via post-synthetic side-chain modification, mimicking post-translational processes. Additionally, as a proof of concept for the synthesis of peptidomimetics on arrays, the integration of an Ugi unit into a growing peptide chain was demonstrated.

Highly efficient Tsuji-Trost allylation in water catalyzed by Pd-nanoparticles.

Palladium nanoparticles stabilized by poly(vinylpyrrolidone) catalyze Tsuji-Trost allylations in water with very high turnover numbers. The di-allylation of methylene active compounds and the allylation of bio-based phenols was performed in high yield. The allylation of lignin showed a high selectivity towards the phenolic OH groups.

Hepatitis B virus covalently closed circular DNA homeostasis is independent of the lymphotoxin pathway during chronic HBV infection.

Current treatment options for patients with chronic hepatitis B virus (HBV) infection are not curative as they are not effective in eliminating covalently closed circular DNA (cccDNA). cccDNA is a stable template for HBV transcription in the nucleus of hepatocytes and is thought to be one of the main factors responsible for HBV persistence. Recently, activation of the lymphotoxin beta receptor (LTßR) has been shown to trigger degradation of cccDNA through induction of cytidine deaminases of the APOBEC3 family in HBV cell culture model systems. To assess the presence and relevance of such mechanisms in the liver of chronically HBV-infected patients, we compared intrahepatic cccDNA levels with the expression levels of lymphotoxins and some of their target genes (eg APOBEC deaminases) in liver biopsy tissue. Our results confirm elevated gene expression levels of components of the lymphotoxin pathway including lymphotoxin alpha (LTα), lymphotoxin beta (LTß), APOBEC3B (A3B) and APOBEC3G (A3G) in the chronically HBV-infected liver compared to uninfected liver. Furthermore, expression levels of the genes of the APOBEC deaminase family were correlated with those of LTα and LTß gene expression, consistent with lymphotoxin-mediated upregulation of APOBEC gene expression. However, intrahepatic cccDNA and HBV replication levels were not correlated with LTα, LTß and APOBEC gene expression. In conclusion, these results suggest that although the lymphotoxin pathway is activated in the chronically HBV-infected liver, it has no major impact on HBV cccDNA metabolism in chronic HBV infection.

Effect of different colored filters on photooxidation in pasteurized milk.

The effect of different colored filters and atmospheres on photooxidation and quality in milk was studied. Pasteurized bovine milk (3.9% fat) was packed in 2 different atmospheres (air and N(2)) and exposed to light for 20 h at 4 degrees C under 8 transparent filters with different light transmission properties. The following transparent, noncolored, and colored filters based on polyethylene terephthalate (PET) were used: noncolored (PET), noncolored with 2 different UV-block regions, yellow, green, amber, orange, and red. Control samples were stored in darkness and in a carton. Sensory evaluation showed off flavors significantly increased in milk stored under all filters compared with the control samples. Variation in atmosphere resulted in significant differences in formation of rancid flavor in milk stored under different filters. Milk samples stored in N(2) underwent the most sensory deterioration under orange and red filters, whereas milk samples stored in air were most deteriorated under noncolored filters. According to the oxidation compounds measured by gas chromatography, milk samples stored under noncolored and orange filters were highly oxidized, whereas red, green, and amber filters offered better protection against photooxidation. Fluorescence spectroscopy was used to examine the degradation of photosensitizers (riboflavin, protoporphyrin, and chlorophyllic compounds) in the milk samples. Degradation of protoporphyrin and chlorophyllic compounds in N(2) correlated well with sensory properties related to photooxidation (R(2)=0.75-0.95). The study indicates that protoporphyrin and chlorophyllic compounds were effective photosensitizers in milk. To avoid photooxidation in milk, it is therefore important to protect it against light from the UV spectrum as well as light from the entire visible region.

Cutting-balloon-associated vascular rupture after failed standard balloon angioplasty.

The following case reports illustrate a possible complication of vascular rupture when cutting balloon dilatation is performed immediately after failed standard balloon angioplasty to the same diameter. Deferral of the cutting balloon dilatation should be considered in such circumstances.

Adiabatic electron thermal pressure fluctuations in tokamak plasmas.

Electron thermal pressure fluctuations measured in the edge plasma of the Texas Experimental Tokamak Upgrade are a fundamental component of plasma turbulence on both sides of the velocity shear layer. The ratio of specific heats, estimated from fluctuations in electron temperature and electron number density measured simultaneously at the same electrode, indicates that observed fluctuations are adiabatic. The observations are made by means of a novel Langmuir probe technique, the time domain triple-probe method, which concurrently measures multiple plasma properties at each of two electrodes with the temporal and the spatial resolution required to estimate thermodynamic properties in a turbulent plasma.

[Coronary fistula associated with severe pulmonary stenosis and cianosis]. / Fístula coronariana associada à estenose pulmonar grave e cianose.

A 17 year old male adolescent was admitted to the hospital due to dyspnea and cyanosis, since the age of 6 years. On physical examination, it was found a continuous murmur over the left esternal border at the 4th and 5th intercostal spaces suggesting a coronary fistula. A color-echocardiogram associated with an angiography confirmed the diagnosis of coronary fistula and severe pulmonary stenosis. The functional consequence was a right to left shunt with cyanosis. A surgical repair was performed with closure of the fistula at the point where it drained into the right ventricle plus a pulmonary commissurotomy. The patient had an uneventful recovery.

Fístula coronariana associada à estenose pulmonar grave e cianose / Coronary Fistula Associated with Severe Pulmonary Stenosis and Cianosis

Adolescente do sexo masculino, 17 anos, com queixa de dispnéia e cianose desde os 6 anos, apresentava ao exame fisíco sopro contínuo nos quarto e quinto espaços intercostais esquerdos, sugestivo de fístula coronariana. O eco-color e a angiografia confirmaram a hipótese de fístula coronariana associada a estenose pulmonar valvar grave e shunt direito-esquerdo, o que provocava a cianose. Foi submetido a correçäo cirúrgica para fechamento da fístula ao nível do seu sítio de drenagem e realizaçäo de cosurotomia pulmonar, permanecendo assintomático até o momento.

Aneurisma subvalvar mitral em criança pós meningite bacteriana / Subvalvar mitral aneurism in child with bacterial meningitis

Os autores relatam um caso de aneurisma subvalvar mitral pós meningite bacteriana aguda, em crianças de cor branca. O aneurisma ventricular surgiu como complicaçäo de uma miopericardite, três semanas após a relaizaçäo de uma pericardiocentese. Foi realizada a resseçäo cirúrgica do aneurisma e a funçäo do ventrículo esquerdo penaneceu inalterada. Säo discutidas as possíveis causas de aneurisma ventricular.

[Surgical treatment of high-risk valvar endocarditis]. / Tratamento cirúrgico da endocardite valvar de alto risco.

The authors have studied the immediate and long term outcome of surgical treatment of acute phase infective endocarditis in a group of 33 high risk patients with valvular heart disease. The age varied from 2 to 68 years, 18 patients were male and 22 were of the white race. The aortic valve was the most frequently involved (18/54.5%), followed by mitral valve (13/39.3%), and tricuspid valve (2/6.0%). Twenty-four patients (72.7%) were in functional class III and seven (21.0%) in functional class IV. The noninvasive studies in those patients revealed 13 cases (39.4%) with normal cardiac size. The EKG was abnormal in 27 cases (81.8%) mostly with left atrial and ventricular hypertrophy. The echocardiogram revealed the presence of vegetations in 27 patients (81.8%) and the blood cultures were positive in 24 cases (72.7%). All patients were treated with antibiotics. The pathologic analysis revealed the presence of vegetations in 94% and structural alterations in 16.5%. Twenty-one patients had heart valve replacement with mechanical prosthesis (63.6%), 11 (33.3%) had bioprosthesis and one had tricuspid excision without replacement (3.0%). The hospital mortality was 12% and the late mortality 3%. Three deaths occurred in patients who had prolonged clinical treatment (more than 35 days) and one patient died of severe fungal endocarditis. The follow-up of the remaining 26 patients varied from 1 to 596 weeks (mean 183) demonstrating important clinical improvement and a normally functioning valve prosthesis. All patients remained in functional class I or II. The analysis of our data indicates that surgical treatment is the best option for high risk endocarditis and should be undertaken earlier in all patients in this group.

[Surgical treatment of high-risk valvular endocarditis]. / Tratamento cirúrgico da endocardite valvular de alto risco.

The authors have studied the short and long term results of surgical treatment of acute phase of infectious endocarditis in a group of 33 high risk patients with valvular heart disease. The age varied from 2 to 68 years; 18 patients were male and 22 were of the white race. The aortic valve was most frequently involved (18/54.5%), followed by the mitral valve (13/39.3%) and tricuspid valve (2/6.0%). Twenty four patients (72.7%) were in functional class III and seven (21%) in functional class IV. The noninvasive studies in those patients revealed 13 cases (39.4%) with normal cardiac size. The ECG was abnormal in 27 cases (81.8%) mostly with left atrial and ventricular hypertrophy. The echocardiogram revealed the presence of vegetations in 27 patients (81.8%) and blood cultures were positive in 22 cases (66.6%). All patients were treated with antibiotics. The pathologic analysis revealed the presence of vegetations in 94% and structural alterations in 16.5%. Twenty-one patients had heart valve replacement with mechanical prosthesis (63.6%), 11(33.3%) had bioprosthesis and one had tricuspid excision without replacement (3.0%). The hospital mortality was 12% and the late mortality 3%. Three deaths occurred in patients who had prolonged clinical treatment (more than 65 days) and one patient died of severe fungal endocarditis. The follow-up of the remaining 26 patients varied from 01 to 448 weeks (mean 183) demonstrating important clinical improvement and a normally functioning valve prostheses. All patients are in functional class I and II. The analysis of our data indicates that surgical treatments is the best option for high risk endocarditis and should be undertaken earlier in all patients in this risk group.

A new technique for repair of mitral insufficiency caused by ruptured chordae of the anterior leaflet.

Prolapse of the anterior leaflet of the mitral valve is the result of ruptured chordae, elongated chordae, or elongated or ruptured papillary muscle. Several techniques have been described for the correction of mitral valve insufficiency. However, when there is severe rupture of the chordae, the most widely accepted solution is valve replacement. We describe a technique for the creation of a neochorda with a strip of tissue from the anterior leaflet of the mitral valve. This technique was used in two patients with severe mitral valve regurgitation. Formation of a neochorda and placement of a Carpentier ring to remodel the anulus obviated the need for a valve replacement. Both patients had an uneventful recovery. Studies performed 3 and 4 months postoperatively showed competent and well-functioning valves. One patient required a valve replacement for acute mitral insufficiency 5 years later, but the other patient was doing well 3 years after the operation. Despite the limited experience, we believe this technique offers a reasonable alternative to valve replacement.

A new technique for repair of aortic coarctation. Subclavian flap aortoplasty with preservation of arterial blood flow to the left arm.

From February 1984 to March 1986, 28 patients underwent a new technique of coarctation repair. This technique consists of a complete mobilization of the left subclavian artery extended to the origin of its first branches. The aorta need not be extensively mobilized and the intercostal arteries are individually controlled with snares. After all the proper clamping, the left subclavian artery is detached from the aorta at its origin and is opened longitudinally on its posterior aspect. The anterior wall of the aorta is then incised, beginning with the opening at the origin of the left subclavian artery and extending distally to the descending aorta 12 to 15 mm past the coarctation. The coarctation membrane is excised and the ductus is ligated and divided. The opened left subclavian artery, now forming a flap, is pulled down and sutured to the edges of the aorta, widening the coarctation site and also preserving the blood flow to the left arm. The ages of the patients ranged from 2 months to 25 years (mean 4.24 +/- 4.9 years) and their weights ranged from 2.8 to 52 kg (mean: 14.8 +/- 10.0 kg). There were no hospital deaths and the mean follow-up was 9.6 months (+/- 4.9 months). Recatheterization of four patients from 4 to 12 months postoperatively showed adequate correction and strongly suggested normal growth of the aorta at the site of coarctation, as well as preservation of the blood flow through the left subclavian artery. Doppler measurements showed normal flow to the left arm and no gradients through the isthmic area. Our experience indicates that this technique is not only feasible but is the procedure of choice in most cases of discrete isthmic coarctation and in some cases of long narrowing of the isthmus in patients with a wide range of ages and weights.

Molecular epidemiology of antibiotic resistance plasmids of Haemophilus species and Neisseria gonorrhoeae.

Ampicillin resistance in Haemophilus influenzae and Neisseria gonorrhoeae is most commonly due to plasmid-mediated production of the TEM beta-lactamase. The H. influenzae plasmids may have evolved by insertion of various antibiotic resistance transposons into a phenotypically cryptic plasmid found in one of 699 isolates of H. influenzae examined. The small, nonconjugative, beta-lactamase-specifying plasmids of N. gonorrhoeae and Haemophilus species are highly related. Phenotypically cryptic plasmids found in several epidemiologically distinct isolates of Haemophilus parainfluenzae are highly related to the beta-lactamase plasmids but carry no transposon A (TnA) sequences. This evidence strongly favors the hypothesis that the beta-lactamase plasmids evolved by the insertion of TnA (possibly introduced from enteric bacteria) into cryptic plasmids resident in H. parainfluenzae.

Anatomia cirúrgica dos tecidos de condução nas cardiopatias congênitas / Surgical anatomy of the conduction system in congenital heart defects

O perigo de lesao do feixe de conducao esta sempre presente na correcao cirurgica das cardiopatias congenitas. E um risco pequeno nos defeitos dos septos atrial e ventricular; ligeiramente maior na tetralogia de Fallot e nos defeitos do septo atrioventricular; tornando-se alto na transposicao das grandes arterias, nos coracoes com valvulas atrioventriculares cavalgadas e consideravelmente elevada na transposicao corrigida (com lesoes associadas) e na septacao dos coracoes com conexao atrioventricular univentricular.Com base na experiencia coletiva dos autores, os tecidos de conducao do coracao foram estudados na sua disposicao e trajetoria normais e tambem do modo como eles podem ser observados pelo cirurgiao nas varias cardiopatias congenitas. Com relativamente poucas regras a posicao e curso dos tecidos de conducao nos coracoes malformados, podem ser localizados e evitados o traumatismo e lesao dessas estruturas.Na experiencia dos autores a incidencia de disturbios da conducao e praticamente nula na correcao das cardiopatias simples e significativamente baixa nas lesoes complexas