Copper (I)-BOX Catalyzed Asymmetric 3-Component Reaction for the Synthesis of Trifluoromethylated Propargylic Ethers and Anilines.

An asymmetric 3-component reaction between EthynylBenziodoXoles (EBXs), 2,2,2-trifluorodiazoethane and nucleophiles catalyzed by a CuI -BOX (Bisoxazoline) catalyst is described. This protocol gives access to chiral trifluoromethylated propargyl ethers and anilines, which are valuable building blocks in synthetic and medicinal chemistry. The reaction proceeds with high enantioselectivity and yield with different nucleophiles such as primary, secondary and tertiary alcohols, as well as both electron-rich and electron-poor anilines. Aryl-, alkyl- and silyl-substituted alkynes can be successfully introduced as electrophiles. In case of chiral substrates, high catalyst control was observed, leading to good diastereoselectivity.

Cu(I)-Catalyzed gem-Aminoalkynylation of Diazo Compounds: Synthesis of Fluorinated Propargylic Amines.

The gem-aminoalkynylation of fluorinated diazo compounds catalyzed by a simple Cu(I) salt is described. This three-component reaction allows the synthesis of propargylic amines with broad functional group tolerance. Both electron-rich and electron-poor anilines can be used as nucleophiles and alkyl-, aryl-, and silyl-substituted EthynylBenziodoXoles (EBX) as electrophiles.

Is aflibercept an optimal treatment for wt RAS mCRC patients after progression to first line containing anti-EGFR?

PURPOSE: To determine the efficacy and safety data of aflibercept + FOLFIRI in wt RAS mCRC patients after progression to standard chemotherapy + anti-EGFR treatment. METHODS: Retrospective, observational study in real life conducted in wt RAS mCRC patients treated with FOLFIRI-aflibercept after progression to standard first line chemotherapy + anti-EGFR treatment. RESULTS: A total of 120 patients from 12 Spanish hospitals were enrolled. Median age is 60 years (62.5%/37.5%male/female). Primary tumor site is 24.1%/75.9% right/left-side colon, and 40.8% of patients had a prior resection. All patients had wild-type RAS tumors including 5% of patients with BRAF mutations and received anti-EGFR treatment. At the time aflibercept was initiated, ECOG PS is 0/1 in 96% of patients. Median number of FOLFIRI-aflibercept cycles is 12. Efficacy results: Overall response rate is 33%; progression-free survival (PFS) is 6.9 months (95%CI: 6.1-7.8). Primary tumor resection was the only significant variable related to PFS in the multivariate analysis. Median overall survival (OS) is 14.5 months (95%CI: 9.7-19.3). ECOG and number of metastatic sites were related to OS in multivariate analysis. About 54.1% of patients received a third-line therapy including TAS-102 (23%), regorafenib (18.5%), and capecitabine (9.2%). TOXICITY: Grade 3-4 toxicities were observed in 37.5% of the patients (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Aflibercept dose was reduced in 18.3% of patients. CONCLUSIONS: The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.

A photoredox-neutral Smiles rearrangement of 2-aryloxybenzoic acids.

We report on the use of visible light photoredox catalysis for the radical Smiles rearrangement of 2-aryloxybenzoic acids to obtain aryl salicylates. The method is free of noble metals and operationally simple and the reaction can be run under mild batch or flow conditions. Being a redox neutral process, no stoichiometric oxidants or reductants are needed.

One-pot synthesis of functionalized bis(trifluoromethylated)benziodoxoles from iodine(I) precursors.

Bis(trifluoromethylated)benziodoxoles (Bx) are broadly used cyclic hypervalent iodine reagents due to their stability and unique chemical properties. However, current methods to access them require several steps and long reaction times, making their synthesis tedious. Herein, a direct one-pot synthesis of bis(trifluoromethylated) Bx reagents from iodine(I) precursors is reported, enabling the synthesis of functionalized reagents.

Decarboxylative Cyanation of Aliphatic Carboxylic Acids via Visible-Light Flavin Photocatalysis.

An operationally simple method is disclosed for the decarboxylative cyanation of aliphatic carboxylic acids at room temperature. Riboflavin tetraacetate, which is an inexpensive organic photocatalyst, promotes the oxidation of carboxylic acids upon visible-light activation. After decarboxylation, the generated radicals are trapped by TsCN, yielding the desired nitriles without any further additive, in a redox-neutral process. Importantly, this protocol can be adapted to flow conditions.

Magnetisation switching of FePt nanoparticle recording medium by femtosecond laser pulses.

Manipulation of magnetisation with ultrashort laser pulses is promising for information storage device applications. The dynamics of the magnetisation response depends on the energy transfer from the photons to the spins during the initial laser excitation. A material of special interest for magnetic storage are FePt nanoparticles, for which switching of the magnetisation with optical angular momentum was demonstrated recently. The mechanism remained unclear. Here we investigate experimentally and theoretically the all-optical switching of FePt nanoparticles. We show that the magnetisation switching is a stochastic process. We develop a complete multiscale model which allows us to optimize the number of laser shots needed to switch the magnetisation of high anisotropy FePt nanoparticles in our experiments. We conclude that only angular momentum induced optically by the inverse Faraday effect will provide switching with one single femtosecond laser pulse.

Photocatalytic Dehydrogenative Lactonization of 2-Arylbenzoic Acids.

A metal-free dehydrogenative lactonization of 2-arylbenzoic acids at room temperature was developed. This work illustrates the first application of visible-light photoredox catalysis in the preparation of benzo-3,4-coumarins, an important structural motif in bioactive molecules. The combination of photocatalyst [Acr(+)-Mes] with (NH4)2S2O8 as a terminal oxidant provides an economical and environmentally benign entry to different substituted benzocoumarins. Preliminary mechanistic studies suggest that this reaction most likely occurs through a homolytic aromatic substitution pathway.

Resolving the role of femtosecond heated electrons in ultrafast spin dynamics.

Magnetization manipulation is essential for basic research and applications. A fundamental question is, how fast can the magnetization be reversed in nanoscale magnetic storage media. When subject to an ultrafast laser pulse, the speed of the magnetization dynamics depends on the nature of the energy transfer pathway. The order of the spin system can be effectively influenced through spin-flip processes mediated by hot electrons. It has been predicted that as electrons drive spins into the regime close to almost total demagnetization, characterized by a loss of ferromagnetic correlations near criticality, a second slower demagnetization process takes place after the initial fast drop of magnetization. By studying FePt, we unravel the fundamental role of the electronic structure. As the ferromagnet Fe becomes more noble in the FePt compound, the electronic structure is changed and the density of states around the Fermi level is reduced, thereby driving the spin correlations into the limit of critical fluctuations. We demonstrate the impact of the electrons and the ferromagnetic interactions, which allows a general insight into the mechanisms of spin dynamics when the ferromagnetic state is highly excited, and identifies possible recording speed limits in heat-assisted magnetization reversal.

Gracilis muscle transplant for correction of traumatic anal incontinence: Report of a case.

We report a case of traumatic anal incontinence successfully treated by the transplant of a gracilis muscle sling, using the technique described by Pickrell et al. in 1952. Although gracilis muscle transplant has been used in the treatment of congenital anal incontinence, its use in traumatic cases has not been widely accepted. Instead, many techniques offering uncertain results have been employed. We believe that Pickrell's technique is a worthwhile procedure in the presence of traumatic anal incontinence, particularly with noniatrogenic large perineal wounds, and that establishment of a temporary colostomy immediately after the injury, together with use of surgical steel sutures and antibiotics, is very helpful in averting posttransplant infection.

Hemorrhoidectomy--how I do it: experience with the St. Mark's Hospital technique for emergency hemorrhoidectomy.

Eighty-five patients who had thrombosed hemorrhoids underwent emergency hemorrhoidectomy according to St. Mark's Hospital technique, with very good results. All specimens were found to have dilated blood vessels filled with thrombi of different sizes, with irregular, fibrotic or hyalinized vascular walls. Early complications included urinary retention and painful defecation in some patients. Late complications included only skin tags. No sepsis was found among our patients. Although operative bleeding can be tedious during the hemorrhoidectomy, it was a complication in the postoperative period of only one patient. Segmental, open hemorrhoidectomy performed according to the St. Mark's Hospital technique has been shown to be an ideal operation for the treatment of patients who have hemorrhoidal thrombosis, prolapse, edema, and bleeding.

[Clinical predictors of long-term outcome of lithium prophylaxis in bipolar disorder]. / Factores predictores de respuesta al litio en pacientes bipolares en seguimiento a largo plazo.

INTRODUCTION: In spite of the frequent prophylactic use of lithium salts in affective disorders, few papers have been published about clinical outcome predictors in long-term follow-up. OBJECTIVE: To identify clinical predictors of long-term outcome in a sample of bipolar outpatients on lithium treatment. METHODS: An intervention study was conducted in a case series of all patients treated, at least for two years, at two Affective Disorders ambulatory Units. It was examined the association between two dependent outcome variables (presence vs absence of relapses and number of relapses/person/year) and the rest of clinical variables. RESULTS: 139 outpatients diagnosed of bipolar disorder were included in the sample. In each case, therapeutic lithium dosages were administered. Delay time to start treatment since the disorder has begun was the only variable useful to predict weakly outcome. The time spent without treatment and the association with other mood stabilizers or neuroleptics correlates with bad outcome. CONCLUSION: Whichever clinical characteristics of the sample may be, patients should be treated as soon as possible with lithium to get better outcome.

Subcutaneous rabies vaccination of pigtail macaques.

Nonhuman primates housed in outside cages in rabies enzootic areas should be vaccinated against rabies because of the risk of exposure to rabid wildlife. This article reports that vaccination with an inactivated rabies vaccine for domestic animals induced levels of neutralizing antibodies against rabies in pigtail macaques (Macaca nemestrina) without causing adverse reactions.

[Effectiveness of lithium in the prophylaxis of affective disorders]. / Efectividad del litio en la profilaxis de las recaídas en pacientes con trastornos afectivos.

UNLABELLED: Lithium effectiveness in manic depressive illness is still controversial. Recent naturalistic trials on lithium effectiveness as a mood stabilizer offer poorer results than previous controlled studies. These previous studies have methodological deficiencies. OBJECTIVE: To determine the effectiveness of lithium treatment as a mood stabilizer under real clinical conditions. METHODOLOGY: An intervention study in a case series of all patients treated at least for two years at two Affective Disorders ambulatory Units was conducted to evaluate the incidence of episodes by year, before and during lithium therapy. RESULTS: 152 patients were included. (91% were bipolar patients). Most of them were in monotherapy. The average time of illness before lithium treatment was 13 years, and cases were followed up a media of 8 years. Only 33% of the sample had no relapses during lithium therapy. An average of 1.38 (+/- 2.89) episodes/person year was estimated previous to lithium therapy and was decreased to 0.35 (+/- 0.47) phases/person year during lithium therapy. CONCLUSIONS: Although the total absence of relapses is not attained in most of the patients, our results support the lithium effectiveness to reduce the relapses in bipolar patients.

A non-invasive technique for the control of intestinal parasites in rhesus macaques (Macaca mulatta).

Control of intestinal parasites is a major concern in maintaining the health and well-being of captive primates. This study established that percutaneous application of ivermectin was as effective as subcutaneous administration for the control of nematodes in captive rhesus macaques. The method is less intrusive than the standard subcutaneous or oral delivery routes and did not adversely affect the health of any of the study subjects.

Efectos tiroideos inducidos por el tratamiento con litio en pacientes con trastornos afectivos / Thyroid effects in lithium-treated patients with affective disordes

FUNDAMENTO: Se investigan la prevalencia y los factores de riesgo del hipotiroidismo clínico y subclínico en pacientes tratados con litio. PACIENTES Y MÉTODO: Se estudiaron todos los pacientes que recibían litioterapia de al menos 2 años de duración. RESULTADOS: La prevalencia de hipotiroidismo clínico y subclínico fue del 10,5 por ciento. La edad elevada al inicio del tratamiento y el sexo femenino se asociaron significativamente con la presencia de hipotiroidismo clínico. CONCLUSIONES: Los factores de riesgo de hipotiroidismo en pacientes tratados con litio son similares a los de la población general (AU)

Efectividad del litio en la profilaxis de las recaídas en pacientes con trastornos afectivos / Effectiveness of lithium in the prophylaxis of affective disorders

Introducción: En la actualidad existe todavía controversia sobre la efectividad del litio como profiláctico, dado que en los estudios observacionales más recientes se obtienen muy pobres resultados, en comparación con los ensayos controlados iniciales, los cuales a su vez presentaban serios problemas metodológicos. Objetivo: Valorar la efectividad del litio como estabilizador del ánimo en condiciones clínicas habituales. Metodología: Diseño: estudio de intervención, con evaluación pre-post en una serie de casos. Muestra: Todos los pacientes en tratamiento durante al menos dos años, en dos Unidades de trastornos afectivos. Se comparó la incidencia de recaídas (por unidad de tiempo) antes y durante el tratamiento con litio. Resultados: Se incluyeron 152 pacientes (91 por ciento bipolares). El tiempo medio de enfermedad antes del tratamiento con litio era de 13 años y durante el tratamiento con litio fue de ocho años. Sólo el 33 por ciento no tuvo ninguna recaída, pero globalmente se alcanzó una disminución significativa de la incidencia de recaídas maníacas y depresivas, pasando de 1,38 (ñ 2,89) antes del litio hasta 0,35 (ñ 0,47) durante la litioterapia. Es decir, se obtuvo una reducción del riesgo de recaídas totales de una fase/persona año1. Conclusiones: Si bien no se obtiene una ausencia total de recaídas en la mayoría de los pacientes, nuestros resultados apoyan la efectividad del litio en la reducción del número de recaídas de los pacientes bipolares. (AU)