Late chronotypes are associated with neoadjuvant chemotherapy-induced nausea and vomiting in women with breast cancer.

Neoadjuvant chemotherapy, that is, the administration of chemotherapy before surgery, has been commonly used for locally advanced breast cancer to improve the surgical outcomes and increase the opportunity for breast-conserving therapy. Women with breast cancer often receive an anthracycline-based regimen as the neoadjuvant chemotherapy, which is associated with a high risk of emesis. Despite the development of novel antiemetics, chemotherapy-induced nausea and vomiting (CINV) has been commonly reported as a major adverse effect, affecting the quality of life of the patients. However, the factors predicting CINV in women with breast cancer undergoing neoadjuvant chemotherapy remain unclear. In this single-institution, prospective, observational study conducted at an outpatient cancer centre in the Republic of Korea from November 2013 to March 2016, we analysed women with breast cancer who planned to be treated with neoadjuvant chemotherapy before surgery. Candidate factors associated with CINV were assessed before neoadjuvant chemotherapy using the Munich Chronotype Questionnaire, Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale. CINV was assessed after chemotherapy by using the Multinational Association of Supportive Care in Cancer Antiemesis Tool. Of a total of 143 participants, 7 patients were lost to follow-up and 2 patients were excluded due to changes in their treatment plan; thus, 134 patients were finally included in the analyses. Overall, 48.5% of the participants experienced CINV, with delayed CINV prevalence (42.5%) being more common than acute (39.6%). In the univariate analyses, overall CINV was significantly associated with late chronotypes (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.37-8.87; p = 0.009), a history of nausea/vomiting (OR, 2.19; 95% CI, 1.10-4.37; p = 0.026) and anxiety (OR, 2.25; 95% CI, 1.05-4.81; p = 0.036). In the multivariate analyses, late chronotypes (OR, 3.53; 95% CI, 1.27-9.79; p = 0.015) and a history of nausea/vomiting (OR, 2.83; 95% CI, 1.31-6.13; p = 0.008) remained significantly associated with CINV. In conclusion, in women with breast cancer undergoing neoadjuvant chemotherapy before surgery, late chronotypes were found to have an increased risk of CINV; these data suggest that clinicians need to assess and consider the chronotype in the management of CINV.

Lifetime prevalence of psychiatric morbidities, suicidality, and quality of life in a community population with the bimodal chronotype: A nationwide epidemiologic study.

Chronotypes are classified as morning, evening, or intermediate, but there are reports of a bimodal type. This study was undertaken to describe the characteristics of the bimodal chronotype and to explore relationships between the bimodal type and psychiatric disorders, fatigue, and quality of life. A total of 2389 subjects from a Korean national epidemiological survey of psychiatric disorders responded during face-to-face interviews. The Korean Composite International Diagnostic Interview was used to diagnose psychiatric disorders, and the Composite Scale of Morningness was used to assess chronotypes. Among intermediate-type subjects, those with a positive bimodal index were classified as bimodal type. In the present study, the proportions of bimodal, morning, intermediate, and evening types were 4.8%, 10.8%, 73.3%, and 11.1%, respectively. Distributions of sociodemographic variables were similar for the bimodal and intermediate types. After controlling for sociodemographic variables, any mood disorder and major depressive disorder were found to be significantly more associated with the bimodal type than the morning type, and dysthymic disorder was significantly more associated with the bimodal type than the intermediate type. For quality-of-life domains, moderate or extreme pain/discomfort was complained about more by subjects with the bimodal type than other types. In summary, the study shows chronotypes differ with respect to their relationships with mood disorder and quality of life. Before the bimodal type is classified as a clinically valid type, further investigations are needed to examine its psychological, physiological, and genetic characteristics.

Phosphoryl azides as versatile new reaction partners in the Cu-catalyzed three-component couplings.

Phosphoryl azide was successfully employed as an efficient reacting partner in the Cu-catalyzed three-component reaction with 1-alkynes and amines to produce the corresponding phosphoryl amidines in high yields. A range of fruitful applicability of the produced amidines was also demonstrated such as an alkoxide exchange and asymmetric alpha-alkylation of optically active BINOL-derived amidines.

Catalytic one-pot synthesis of cyclic amidines by virtue of tandem reactions involving intramolecular hydroamination under mild conditions.

A new synthetic methodology for the generation of cyclic amidines has been developed by the reaction of 1,n-aminoalkynes with electron-deficient azides using a ruthenium catalyst at ambient temperature. The reaction proceeds most likely via a tandem sequence of intramolecular hydroamination of aminoalkynes, cycloaddition of azides with the resulting enamines, and rearrangement of triazoline intermediates. It demonstrates, as the proof-of-principle, that an equilibria cascade sequence can be favorably driven by an irreversible step, thus enabling a facile one-pot synthetic route to deliver molecular complexity under unprecedented mild conditions without relying on the traditional linear approaches.

Hydrogen-bond-directed highly stereoselective synthesis of Z-enamides via Pd-catalyzed oxidative amidation of conjugated olefins.

An efficient procedure for the preparation of Z-enamides has been developed, involving the reaction of primary amides with conjugated olefins using a Pd/Cu cocatalyst system. It was found that certain additives, such as phosphine oxides and phosphonates, increase the efficiency of the reaction in nonpolar solvents under an oxygen atmosphere, thus producing a variety of Z-enamides in high yields with excellent stereoselectivity under Wacker-type conditions. The oxidative amidation reaction has a broad substrate scope, allowing alkyl, aryl, and vinyl amides to react with olefins conjugated with ester, amide, phosphonate, and ketone groups. The notable preference for the formation of Z-enamides is presumably due to the presence of an intramolecular hydrogen bond between the amido proton and the carbonyl oxygen. The energy difference between two plausible sigma-alkylamidopalladium intermediates, leading to Z- and E-isomeric enamide products, respectively, was calculated to be 4.18 kcal/mol. The beta-hydride elimination step is assumed to be a stereochemistry-determining step in the overall oxidative amidation process, with the energy level for the transition state leading to the Z-enamide being 5.35 kcal/mol lower than that leading to the E-isomer. The efficiency of photoisomerization between Z- and E-enamides was observed to be largely dependent on the substrates' substituents, and certain E-enamides could be obtained in synthetically useful yields by photoirradiation of Z-isomers. Synthetic application of the present method was successfully demonstrated by a direct formal synthesis of cis-CJ-15,801.