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A total of 8 geriatric medicine fellows participated in an objective structured clinical examination (OSCE) assessing communication skills and clinical reasoning in common geriatric syndromes. To determine their perceptions about the experience, we conducted surveys and semistructured interviews. We analyzed the survey data using descriptive statistics, and two researchers independently utilized the constant comparative method to code themes from the interview transcriptions. Most perceived the OSCE as a formative tool, and many were concerned that the exam did not accurately measure real-world competence. In conclusion, fellows considered the OSCE to be valuable for reinforcing skills relevant to geriatric medicine but had concerns of exam validity. [ABSTRACT FROM AUTHOR]

Plant proteins are increasingly being used in the food industry due to their sustainability. They can be isolated from food industry waste and converted into value-added ingredients, promoting a more circular economy. In this study, ultrasound-assisted alkaline extraction (UAAE) was optimized to maximize the extraction yield and purity of protein ingredients from grapeseeds. Grapeseed protein was extracted using UAAE under different pH (9-11), temperature (20-50 °C), sonication time (15-45 min), and solid/solvent ratio (10-20 mL/g) conditions. The structural and functional attributes of grapeseed protein and its major fractions (albumins and glutelins) were investigated and compared. The albumin fractions had higher solubilities, emulsifying properties, and in vitro digestibilities but lower fluid binding capacities and thermal stability than the UAAE and glutelin fraction. These findings have the potential to boost our understanding of the structural and functional characteristics of grapeseed proteins, thereby increasing their potential applications in the food and other industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

A curious and noticeable structural feature in Schiff bases from 2-aminoaldoses is the fact that imino tautomers arranged equatorially in the most stable ring conformation exhibit a counterintuitive reverse anomeric effect (RAE) in the mutarotational equilibrium, i.e., the most stable and abundant anomer is the equatorial one (β). As shown by our very recent research, this effect arises from the total or partial inhibition of the exo-anomeric effect due to the presence of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen in the axial anomer (α). When the Schiff base adopts either an enamine structure or the imino group is protonated, the exo-anomeric effect is restored, and the axial α-anomer becomes the most stable species. Although the intramolecular H-bonding should appropriately be interpreted as a genuine stereoelectronic effect, the magnitude of the RAE could be affected by other structural parameters. Herein and through a comprehensive analysis of benzylidene, cinnamylidene, naphthalene, phenanthrene, and anthracene aldehydes, we show the robustness of the RAE effect, which is similar in extent to simple aldehydes screened so far, irrespective of the size and/or hydrophobicity of the substituent at the nitrogen atom.

The reverse anomeric effect is usually associated with the equatorial preference of nitrogen substituents at the anomeric center. Once postulated as another anomeric effect with explanations ranging from electrostatic interactions to delocalization effects, it is now firmly considered to be essentially steric in nature. Through an extensive research on aryl imines from 2-amino-2-deoxyaldoses, spanning nearly two decades, we realized that such substances often show an anomalous anomeric behavior that cannot easily be rationalized on the basis of purely steric grounds. The apparent preference, or stabilization, of the β-anomer takes place to an extent that not only neutralizes but also overcomes the normal anomeric effect. Calculations indicate that there is no stereoelectronic effect opposing the anomeric effect, resulting from the repulsion between electron lone pairs on the imine nitrogen and the endocyclic oxygen. Such data and compelling structural evidence unravel why the exoanomeric effect is largely inhibited. We are now confident, as witnessed by 2-iminoaldoses, that elimination of the exo-anomeric effect in the α-anomer is due to the formation of an intramolecular hydrogen bond between the anomeric hydroxyl and the iminic nitrogen, thereby accounting for a true electronic effect. In addition, discrete solvation may help justify the observed preference for the β-anomer.

This paper explores and revisits in detail the formation and characterization of sugar-based aminonitriles, whose ultimate origin can be traced to the interaction of biomolecules with cyanide. Although the synthesis and spectroscopic data of 2-amino-aldononitriles were reported long ago, there are both contradictory and confusing results among the published data. We have now addressed this concern through an exhaustive structural elucidation of acylated 2-amino- and 2-alkyl(aryl)amino-2-deoxyaldonitriles using mass spectrometry and FT-IR, FT-Raman, and NMR spectroscopies. Several structures could be unambiguously determined through single-crystal X-ray diffraction, which allowed us to correct other misassignments. Moreover, this study unveils how steric and electronic effects influence the acylation outcome of the amino, (alkyl, aryl)amino, or acetamido group at C-2. The chirality at the latter, which was assigned tentatively through optical rotation correlation, and hence the preferential threo stereochemistry generated during the cyanohydrin synthesis of 2-amino-2-deoxy aldononitriles have now been established with confidence.

This paper stems from the hypothesis that there are various key factors rooted in economic, political, and social grounds which actively influence and determine the adoption and evolution of LGBT+ rights in the legal framework of any country. The goal of this research is to analyze these factors and understand how they channel the LGBT+ legislation in our present world. Assuming there is an asymmetry in this application and by extension in LGBT+ individuals' human rights, which are often ignored if not deprived in many parts of the world, this study seeks to understand the reasons behind that asymmetry. Based on a sample of 127 countries, a correlation analysis and a Panel data model were developed to analyze the real impact of these factors.

Olive leaf, as an important by-product of olive farming, is generated from the pruning and harvesting of olive trees and represents >10 % of the total olive weight. The present study was conducted to evaluate the composition, functional and structural characterizations, as well as the in vitro digestibility of olive leaf proteins isolated from ultrasonic-assisted extraction, comparing to classical and industrial techniques. The ultrasound-assisted extraction of olive leaf protein was optimized by the simultaneous maximization of the yield and purity of protein using a Box-Behnken design (BBD) of response surface methodology (RSM). The results indicated that the optimal extraction conditions were as follows: pH of 10.99, temperature of 40.48 °C, sonication time of 47.25 min, and solvent/solid ratio of 24.08 mL/g. Under these conditions, the extraction yield and protein content were 11.67 and 51.2 %, respectively, which were significantly higher than those obtained by the conventional techniques. Regarding the functionality of protein, extraction technique had significant impacts on the structural and functional properties of proteins. In general, ultrasound assisted extraction had higher solubility, and better foaming and thermal properties and in vitro digestibility but lower emulsifying stability and fluid binding capacity compared to conventional ones. Ultrasound-assisted alkaline extraction has great potential to produce edible olive leaf protein with modified functional properties that can be used for various aims in the food applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Thirty-nine aryl azoles, thirteen triazoles and twenty-seven tetrazoles, have been synthetized and biologically evaluated to determine their activity as tumor microenvironment disruptors. Antiproliferative studies have been performed on tumor cell lines HT-29, A-549 and MCF-7 and on non-tumor cell line HEK-293. It has been studied in HT-29 the expression levels of biological targets which are involved in tumor microenvironment processes, such as PD-L1, CD-47, c-Myc and VEGFR-2. In addition, antiproliferative activity was evaluated when HT-29 were co-cultured with THP-1 monocytes and the secretion levels of IL-6 were also determined in these co-cultures. The angiogenesis effect of some selected compounds on HMEC-1 was also evaluated as well as their action against vasculogenic mimicry on HEK-293. Compounds bearing an amino group in the phenyl ring and a halogen atom in the benzyl ring showed promising results as tumor microenvironment disrupting agents. The most outstanding compound decrease dramatically the population of HT-29 cells when co-cultured with THP-1 monocytes and the levels of IL-6 secreted, as well as it showed moderate effects over PD-L1, CD-47 and c-Myc., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

This paper thoroughly explores the formation of Schiff bases derived from salicylaldehydes and a conformationally restricted amino alcohol (1-amino-2-indanol), as well as the generation of 1,3-oxazolidines, a key heterocyclic core present in numerous bioactive compounds. We provide enough evidences, both experimental-including crystallographic analyses and DFT-based calculations on imine/enamine tautomerism in the solid state and solution. In the course of imine formation, a pentacyclic oxazolidine-oxazine structure could be isolated with complete stereocontrol, whose configuration has been determined by merging theory and experiment. Mechanistic studies reveal that, although oxazolidines can be obtained under kinetic conditions, the prevalence of imines obeys to thermodynamic control as they are the most stable structures. The stereochemical outcome of imine cyclization under acylating conditions leads to formation of 2,4- trans -oxazolidines.

Plant-based proteins are gaining in attraction compared with animal-based proteins due to their superior ethical profiles, growing concerns on the part of various organizations about animal health and welfare, and increased global greenhouse-gas emissions in meat production. In this study, the response surface methodology (RSM) using a Box-Behnken design (BBD) was applied to optimize the ultrasound-assisted alkaline extraction of cherimoya-seed proteins as valuable by-products. The effects of three pH, temperature, and time factors on the protein-extraction yield and protein content were investigated. The pH at 10.5 and temperature of 41.8 °C for 26.1 min were considered the optimal ultrasound-assisted alkaline-extraction conditions since they provided the maximum extraction yield (17.3%) and protein content (65.6%). An established extraction technique was employed to enhance the cherimoya-seed protein yield, purity, and functional properties. A thermogravimetric analysis (TGA) of the samples showed that the ultrasound-assisted alkaline extraction improved the thermal stability of the protein concentrate.

In recent years, there has been a growing interest in the application of antioxidants in food and pharmaceuticals due to their association with beneficial health effects against numerous oxidative-related human diseases. The antioxidant potential can be measured by various assays with specific mechanisms of action, including hydrogen atom transfer, single electron transfer, and targeted scavenging activities. Understanding the chemistry of mechanisms, advantages, and limitations of the methods is critical for the proper selection of techniques for the valid assessment of antioxidant activity in specific samples or conditions. There are various analytical techniques available for determining the antioxidant activity of biological samples, including food and plant extracts. The different methods are categorized into three main groups, such as spectrometry, chromatography, and electrochemistry techniques. Among these assays, spectrophotometric methods are considered the most common analytical technique for the determination of the antioxidant potential due to their sensitivity, rapidness, low cost, and reproducibility. This review covers the mechanism of actions and color changes that occur in each method. Furthermore, the advantages and limitations of spectrophotometric methods are described and discussed in this review.

Polyhydroxylated phenols are components of biomass and precursors of pigments in plants. This paper reports a novel entry to xanthene dyes, involving the reaction of 2,4,6-trihydroxybenzaldehyde with primary aliphatic amines. This catalyst-free synthesis exhibits a high atom economy and can be conducted under eco-friendly conditions and operational simplicity.

An ultrasound-assisted method was used for the extraction of phenolics from defatted black cumin seeds ( Nigella sativa L.), and the effects of several extraction factors on the total phenolic content and DPPH radical scavenging activity were investigated. To improve the extraction efficiency of phenolics from black cumin seed by ultrasonic-assisted extraction, the optimal extraction conditions were determined as follows: ethanol concentration of 59.1%, extraction temperature of 44.6 °C and extraction time of 32.5 min. Under these conditions, the total phenolic content and DPPH radical scavenging activity increased by about 70% and 38%, respectively, compared with conventional extraction. Furthermore, a complementary quantitative analysis of individual phenolic compounds was carried out using the HPLC-UV technique. The phenolic composition revealed high amounts of epicatechin (1.88-2.37 mg/g) and rutin (0.96-1.21 mg/g) in the black cumin seed extracts. Ultrasonic-assisted extraction can be a useful extraction method for the recovery of polyphenols from defatted black cumin seeds.

Background: Operative vaginal birth represents an alternative to address problems during the second stage of labor. Obstetricians have access to three different instruments: forceps, vacuum, and spatulas., Objective: To evaluate the safety and effectiveness of the use of spatulas for operative vaginal birth., Search Strategy: MEDLINE/PubMed, Embase, CENTRAL, LILACS, SciELO, ClinicalTrials.gov, and OpenGrey., Selection Criteria: Randomized controlled studies and non-randomized controlled studies (NRS) were included., Data Collection and Analysis: Studies were independently assessed for inclusion, data extraction, and risk of bias., Main Results: Nine NRS (n = 16  497 women) compared the use of spatulas versus forceps. Low-certainty evidence suggests that spatulas were not different in terms of failed operative vaginal delivery rate (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.53-1.52), but may decrease the incidence of birth canal trauma (OR 0.70, 95% CI 0.54-0.91), birth canal laceration (OR 0.50, 95% CI 0.28-0.91), and neonatal soft-tissue injury (OR 0.19, 95% CI 0.13-0.29). Six NRS (n = 2992 women) compared the use of spatulas versus vacuum. Low-quality evidence suggests that spatulas may decrease failed operative vaginal delivery rate (OR 0.10, 95% CI 0.04-0.26). There were no apparent differences in other maternal and neonatal outcomes., Conclusion: Low-certainty evidence suggests that spatulas could be a safe and effective alternative for operative vaginal birth., (© 2021 International Federation of Gynecology and Obstetrics.)

The facile reaction of a readily available aminopolyol from the chiral pool, N-methyl-d-glucamine, which avoids the side reactions usually associated to anomers of amino sugars, with epoxide and polyepoxide derivatives, enables the preparation of new non-ionic surfactant-like structures combining hydrophilic and hydrophobic moieties. The molecular architectures thus obtained range from linear to tripodal and pyramidal structures. The resulting substances containing multiple chiral centers exist as diastereomeric mixtures, for which various conformations are likewise possible by virtue of inter-chain interactions. The stability and chirality preferences of all possible stereoisomers have been evaluated in detail by DFT methods. Given the amphiphilic structure of both protected and O-protected derivatives obtained by acetylation, self-aggregation could eventually lead to solvent entrapment. Unfortunately, only one compound behaves as efficient hydrogelator and DMSO-gelator at low concentrations. The issue is also discussed in terms of the different molecular arrangements., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This article describes harassment practices in higher education and explains why they are taken for granted, besides documenting forms of resistance reported by some students and professors. From January 2016 to March 2017, nine in-depth interviews were held with students who had experienced harassment at a public school of law in Mexico City, Mexico, besides interviews with three male students and two female professors. The findings suggest that some professors harass selectively, based on dress codes associated with gender stereotypes. Harassment can be viewed as an exemplary punishment with corrective purposes, or part of school discipline and the formation of female students' identity at the institution. The study also detected forms of heteronormative vigilance that take harassment for granted, to the degree that some female students consider it part of a lifestyle to which they have to adapt in order to complete their studies. Other female students have found ways of denouncing harassment, through informal strategies by which they have contributed to exposing and denaturalizing this gender violence. For example, some professors have ordered female students to wear skirts when taking exams, but this order is not always obeyed, and the students that have refused have organized resistance movements. Thus far there has been no intervention by the university administration to guarantee harassment-free spaces for women, which highlights the need to create guidelines and rules for higher education that allow typifying such acts as serious offenses and preventing sexual harassment.

It has been suggested that high altitude can reduce the infectivity and case fatality rate of COVID-19. We investigated the relationship between altitude and the COVID-19 pandemic in Colombia. Epidemiological data included the number of positive cases, deaths, and the case fatality rate of COVID-19. In particular, we analyzed data from 70 cities with altitudes between 1 and 3,180 m. Correlations and linear regression models adjusted to population density were performed to examine the relationship and contribution of altitude to epidemiological variables. The case fatality rate was negatively correlated with the altitude of the cities. The incidence of cases and deaths from COVID-19 had an apparent correlation with altitude; however, these variables were better explained by population density. In general, these findings suggest that living at high altitude can reduce the impact of COVID-19, especially the case fatality rate.

Imine and enamine bonds decorate the skeleton of numerous reagents, catalysts, and organic materials. However, it is difficult to isolate at will a single tautomer, as dynamic equilibria occur easily, even in the solid state, and are sensitive to electronic and steric effect, including π-conjugation and H-bonding. Here, using as model Schiff bases generated from salicylaldehydes and TRIS in a set of linear free energy relationships (LFER), we disclose how the formation of either imines or enamines can be controlled and provide a comprehensive framework that captures the structural underpinning of this prediction. This work highlights the potentiality of tailor-made designs en route to compounds with desirable functionality.

A one-pot procedure for preparing a series of chiral imines by direct condensation of d-glucamine with 2-hydroxyacetophenones is described. Under conventional acetylation an unexpected mixture of two different peracetylated molecules is obtained, one with an open enamine structure, and the other incorporating an N-acetyl-1,3-oxazolidine into the acyclic skeleton. Surprisingly, both molecules coexist within the crystal's unit cell, as inferred from single-crystal X-ray analysis of a 5-bromo-substituted aryl derivative. Moreover, the 1,3-oxazolidine ring exists as rotational conformers (E,Z) owing to the restricted rotation around the N-acetyl bond. The equilibrium involving imine and enamine structures has been assessed in detail, providing in addition linear free-energy relationships between the tautomerization constants (K T ) and the electronic effect of the substituents.

Tautomerism plays a pivotal role in structural stabilization and reactivity. Herein we investigate in detail, aided by DFT simulations, the case of gossypol, a naturally occurring atropisomeric dialdehyde showing promising properties as a male contraceptive and an antineoplasic agent. Its toxicity linked to reactive aldehydo groups can be reduced through amino conjugation. The occurrence of either imino or enamino structures is puzzling indeed and a clear-cut rationale is missing yet. N-enamine-N-enamine structures are prevalent or exclusive tautomers for Schiff bases from gossypol, while their corresponding hydrazones only possess N-imine-N-imine structures both in solution and the solid state. The modification of interactions between the lone pairs on the nitrogen atoms by altering the steric hindrance of the non-iminic nitrogen can favor enamine tautomers. This assumption has now been confirmed and, in the solid state, hydrazones from N-aminopiperidine and their cis-2,6-dimethylderivative present bis-imine and bis-enamine structures, respectively. In solution, these compounds exist in equilibrium between both structures. The tautomerization mechanism, analysis of axial chirality and aromaticity in such H-bonded pseudorings are discussed as well.

A paucity of research exists on medical student pressure ulcer education., Purpose: This study examines medical student competency outcomes following implementation of a competency-based curriculum that included a pressure ulcer component in its educational intervention., Methods: Over a 5-year period, 645 medical students completed the curriculum, which included a preceptor-led didactic session, online study resources, clinical experiences, and a brief online competency assessment. The assessment involved knowledge of risk factors, wound staging/classification, and prevention and management strategies and included short answer and extended matching questions. A performance standard was set; students not achieving this standard underwent remediation and reassessment. The curriculum was implemented in 3 phases with quality improvement (QI) between each phase. The average competency assessment score and passing rates were determined for each phase. Mean scores for each phase were compared using an analysis of variance test., Results: Mean competency assessment scores increased significantly after each QI from 17.5 (range 11-23) to 18.3 (range 12-24) to 19.8 (range 12-25) in phases 1, 2 and 3, respectively [F(2,642) = 59.502, P <.001]; the performance standard was raised after both QI points. Overall, 8.7% of students underwent remediation and reassessment, but all achieved the performance standard on their second attempt., Conclusion: Through a thoughtful QI process that involved carefully aligning all curricular elements (the instructional activities and the assessment), a focused and accountable curriculum was developed that ensured all medical students in the program would achieve a basic level of competency. Increasingly, accreditation agencies are asking medical schools to move toward competency-based curricula. This curriculum represents an important step in this direction.

We report a detailed investigation into the nature of products that are generated by the reactions of cyanamide and glyoxal, two small molecules of astrochemical and prebiotic significance, under different experimental conditions. The experimental data suggest that the formation of oligomeric structures is related in part to the formation of insoluble tholins in the presence of oxygen-containing molecules. Although oligomerization proceeds well in water, product isolation turned out to be impractical. Instead, solid precipitates were obtained easily in acetone. Crude mixtures have been thoroughly scrutinized by spectroscopic methods, in particular NMR and mass spectroscopy (ESI mode), which are all consistent with the generation of a few functional groups that are embedded into regular chains of five- and six-membered rings, thereby pointing to a supramolecular organization. Three different models of cross-condensation and chain growth are suggested. These synthetic explorations provide further insights into the formation of complex organic matter in interstellar scenarios and extraterrestrial bodies that might have played a pivotal role in chemical evolution., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Endometrial carcinoma comprises a group of tumours with distinct histologic and molecular features and clinical behaviour. Here, we sought to define the biological processes that govern the clinical behaviour of endometrial cancers., Methods: Sixteen prototype genes representative of different biological processes that would likely play a role in endometrial and other hormone-driven cancers were defined. RNA-sequencing gene expression data from 323 endometrial cancers from The Cancer Genome Atlas (TCGA) were used to determine the transcription module of each prototype gene. The expression of prototype genes and modules and their association with outcome was assessed in univariate and multivariate survival analyses. The association of MSH6 expression with outcome was validated in an independent cohort of 243 primary endometrial cancers using immunohistochemistry., Results: We observed that the clinical behaviour of endometrial cancers as a group was associated with hormone receptor signalling, PI3K pathway signalling and DNA mismatch repair processes. When analysed separately, in endometrioid carcinomas, hormone receptor, PI3K and DNA mismatch repair modules were significantly associated with outcome in univariate analysis, whereas the clinical behaviour of serous cancers was likely governed by apoptosis and Wnt signalling. Multivariate survival analysis revealed that MSH6 gene expression was associated with outcome of endometrial cancer patients independently from traditional prognostic clinicopathologic parameters, which was confirmed in an independent cohort at the protein level., Conclusion: Endometrioid and serous endometrial cancers are underpinned by distinct molecular pathways. MSH6 expression levels may be associated with outcome in endometrial cancers as a group., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We revisit herein the formation and structure of dihydroxy dioxanes, which can be obtained from prebiotically available precursors and can be regarded as primeval sugar surrogates. Previous studies dealing with the heterogeneous composition of interstellar bodies point to the existence of significant amounts of small polyalcohols along with oxygen-containing oligomers. Even though such derivatives did not give rise to nucleosides and oligonucleotides, nor they were incorporated into subsequent metabolic routes, molecular chimeras based on sugar-like species could be opportunistic scaffolds in pre-evolutionary scenarios. We could figure out that pseudosugars, assembled by hemiacetalic bonds from available precursors in both interstellar and terrestrial scenarios, were presumably more abundant than thought. Moreover, these species share some key features with naturally-occurring sugar rings, such as anomeric preferences, coordinating ability, and the prevalent occurrence of racemic compounds.

Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Monoaza- and diaza-derivatives of malondialdehydes, in short aminoacroleins and vinamidines, are prototypical examples of open-chain structures prone to π-electron delocalization, for which intramolecular hydrogen bonding enhances (or diminishes) their pseudoaromaticity depending on the substitution pattern. This interplay is illustrated herein by DFT-based calculations of aromaticity indices in the gas phase and polar solvents. Elucidation of transition structures involved in tautomeric conversions helps to solve how the intramolecular hydrogen transfer occurs. While TSs exhibit a high degree of aromaticity, the dichotomy between forward and backward pathways points to a complex trajectory. Addition of thermal corrections to the electronic energy decreases both the enthalpy and free energy leading to negative ΔH(‡) and ΔG(‡) values. This variational effect accounts for the otherwise elusive distinction between transition structures and saddle points (usually overlooked for high electronic barriers). Also, this rationale fits well within the framework of Marcus' theory.

Mono- and diaza-derivatives of malondialdehydes, namely 3-alkyl(aryl)amino-2-arylacroleins and 1,5-dialkyl(aryl)-3-arylvinamidines are open-chain systems in which extended electron delocalization and pseudoaromaticity can be envisaged. A set of diversely functionalized compounds has been synthesized and characterized by spectroscopic data and X-ray diffractometry. Quantum-chemical calculations were performed for all possible neutral tautomers and conformers in the gas phase and compared to those in polar solvents (CHCl3, DMSO, and EtOH) at the M06-2X/6-311++G(d,p) level. Tautomeric equilibria and conformational preferences can be rationalized in terms of structural factors, which can be roughly estimated as summation or subtractions of intramolecular interactions. As expected, a key role is played by intramolecular hydrogen bonds whose strength varies from the gas phase to polar ethanol. This issue also delves into the concept of resonance-assisted H-bond, where the donor and acceptor atoms are connected by a π-conjugated system. The most stable conformers (structures a and c) possess a high degree of pseudoaromaticity as inferred from HOMA indexes and other delocalization parameters.

An improved preparation of mesoionic heterocycles 1,3-diazolium-4-thiolates by [3 + 2] cycloadditions of münchnones with aryl isothiocyanates is reported. The process takes place with high or complete regioselectivity, and fast and clean transformations are observed under microwave heating in DMF. DFT calculations support that this cycloaddition proceeds preferably through a stepwise mechanism. Given the pattern substitution around the mesoionic ring resulting in a push-pull system, theoretical estimations predict large hyperpolarizabilities in some cases, which is typical of molecules exhibiting nonlinear optical responses.

What accounts for a particular chiral selection in the case of a few sugars of prebiotic relevance, thereby mirroring the asymmetry observed in nature? By using first-principles calculations, the generation of pentoses from glycolaldehyde (the initial product of the autocatalytic formose reaction), which has been detected in outer space), has been modeled by using L-Val-L-Val as a primeval catalyst. Our theoretical study provides insight into the mechanism of this reaction and satisfactorily explains a few key molecular events. Our rationale agrees with the reported experimental data and shows that the D-configuration is only favored for ribose. L-pentoses are usually favored in the presence of L-configured dipeptides, as observed experimentally, although no chiral selection could be observed in the case of xylose. These results confirm that a prebiotic sugar soup could be fine-tuned in the presence of shorter peptides as catalysts and that D-ribose would have also resulted in an advantageous imbalance for further amplification and chemical evolution., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Schiff bases derived from hydroxyl naphthaldehydes and o-substituted anilines have been prepared and their tautomerism assessed by spectroscopic, crystallographic, and computational methods. Tautomeric equilibria have also been studied and reveal in most cases a slight preference of imine tautomers in solution; a fact supported by DFT calculations in the gas phase as well as incorporating solvent effects through the SMD model. To simulate the effect exerted by the crystal lattice on tautomer stability, we have developed a computational protocol in the case of 1-tert-butyl-2-(2-hydroxy-1-naphthylmethylene)aminobenzene whose data have been obtained experimentally at 120 K. Although a rapid imine-enamine interconversion may be occurring in the solid state, the imine tautomer becomes the most stable form and the energy difference should be related to the difference in the packing of the molecules.

The azide-alkyne cycloaddition assisted by a self-assembled molecular flask developed by Rebek and coworkers (Org. Lett., 2002, 4, 327) has been simulated by means of the ONIOM methodology, thereby evidencing the reliability of this theoretical approach to model such large encapsulated systems. Experimental evidences accounting for this transformation within the supramolecular assembly such as the significant rate enhancement, complete regioselectivity, and product inhibition as the reaction proceeds have been qualitatively disentangled through estimation of the energy barriers and the structural characteristics of the corresponding host-guest complexes.

The conformational population of Z and E isomers of the amide bond in N-acetyl oxazolidines is dictated by the electronic nature of the vicinal aryl ring. Experimental and theoretical data support a rationale based on a strong and stereodirecting charge-charge interaction that should be added to the arsenal of non-covalent interactions and whose influence can be more important than once thought.

The archetypal Cu(I)-catalyzed alkyne-azide click cycloaddition (CuAAC) has been explored thoroughly via density functional calculations, modeling copper nuclei with the LANL2DZ basis set and aqueous environments with CPCM solvation. All the mechanistic proposals, ranging from the intermediacy of copper acetylides to π-complexes and multinuclear clusters have been compared. The known features of the CuAAC reaction such as the observed second order kinetics for the Cu(I) species and the marked regioselectivity have been taken into account. The calculated energy barriers point to the intermediacy of copper(i) acetylides with two metal centers, in agreement with the observed kinetics, which exhibit barriers of 10.1 kcal mol(-1) and 13.7 kcal mol(-1) for the 1,4- and 1,5-regiochemistries, respectively, thus accounting for the marked regioselectivity of the copper catalyzed azide-alkyne cycloaddition. The copper acetylide versus π-complexes dilemma has also been experimentally addressed through the click reaction of benzyl azide and isotopically labeled phenylacetylene. The total proton/deuterium exchange in the afforded triazole demonstrates the formation of a copper acetylide intermediate during the transformation.

The transformation of münchnones (mesoionic rings featuring the 1,3-oxazolium-5-olate core) into their sulfur counterparts (1,3-thiazolium-5-thiolates) by reaction with CS(2), pioneered by Huisgen and his group in the early 1970s, has been re-investigated in detail by means of both experimental and theoretical methods. The synthetic strategy can be tuned to incorporate donor and acceptor groups in appropriate positions. Calculations of molecular hyperpolarizabilities together with orbital topologies evidence that these sulfur-containing heterocycles exhibit nonlinear optical responses, thereby pointing to potential applications of mesoionic structures in the NLO field. From a mechanistic viewpoint, modeling of the whole systems at the B3LYP/6-31G(d) level reveals that concerted and stepwise pathways are operative depending on the substitution pattern of the parent münchnone, which also account for the experimental results.

An intramolecular S(N)Ar mechanism has been identified in the unexpected aryl migration observed in a mesomeric betaine. The process changes drastically the optical and spectroscopic properties and should be a valuable model for related heteroaromatic systems.

This paper describes a methodology that correlates experimental chemical shifts (at the alpha proton) of proteins with their geometrical data (both dihedral angles and distances) obtained from 13 representative proteins, which are taken from the Protein Data Bank (PDB) and the BioMagRes Data Bank (BMRB). To this end, the experimentally measured proton chemical shifts of simple amides have been correlated with DFT-based calculated structures, at the B3PW91/6-31G* level. This results in a series of mathematical relationships, which are extrapolated to the above-mentioned proteins giving rise to a modified equation for such skeleta. It is relevant to note that the equation is also supported by a clear comparison with NMR data of a protein beyond the chosen set, such as insulin, even with lower errors. The model also relates the dependence of chemical shifts on hydrophobic and anisotropic effects at the amino acid residues.

Despite the comprehensive literature and enormous versatility of chiral imines derived from aminosugars and aldehydes, the corresponding counterparts generated from ketones remain an underestimated research subject. Filling in the gap, this manuscript sheds light on the synthetic and structural aspects of such substances and updates the few antecedents reported so far., (Copyright 2009 Elsevier Ltd. All rights reserved.)

This paper documents in detail the reaction of 1,3-thiazolium-4-olates (thioisomunchnones) with aryl isothiocyanates. Having demonstrated with a chiral model that thionation occurs under these conditions to provide 1,3-thiazolium-4-thiolates and that this process is actually a stepwise domino reaction (J. Org. Chem. 2009, 74, 3698-3705), we extend this study to monocyclic thioisomunchnones. Herein, competition between thionation and 1,3-dipolar cycloaddition takes place. The process is synthetically disappointing at room temperature requiring prolonged reaction times for completion. The protocol has been subsequently investigated by using both microwave dielectric heating and conventional thermal heating (oil bath) in DMF at 100 degrees C with an accurate internal reaction temperature measurement. Although a slight acceleration was observed for reactions conducted under microwave irradiation, for most cases the observed yields and chemoselectivities were quite similar. Thus one can conclude that, within experimental errors, the reactivity is not related to nonthermal effects in agreement with recent reassessments on this subject, particularly by Kappe and associates (J. Org. Chem. 2008, 73, 36; J. Org. Chem. 2009, 74, 6157). The whole reaction system, which includes numerous heavy atoms, can be computationally modeled with a hybrid ONIOM[B3LYP/6-31G(d):PM3] level. This reproduces well experimental results and suggests a sequential mechanism. To further corroborate the nonconcertedness, the potential energy surface (PES) has been constructed for simplified models, locating the corresponding stationary points. In doing so, we introduce for the first time a useful and convenient mathematical protocol to locate the stationary points along a reaction path. The protocol is quite simple and should convince many organic chemists that certain daunting theoretical treatments can be made easy.

Nalbuphine and tramadol are potent analgesic drugs. Our aim was to preliminarily assess and compare the efficacy and safety of nalbuphine and tramadol for postoperative analgesia in children. In a double-blind design, 24 ASA 1-3 children aged 1 to 10 years undergoing a scheduled surgical procedure were randomly allocated to receive either an intravenous bolus dose of nalbuphine 100 microg/kg immediately before the end of surgery followed by an infusion of 0.2 microg/kg/min for 72 hrs., or an intravenous bolus dose of tramadol 1000 microg/kg followed by an infusion of 2.0 microg/kg/min for 72 hrs. Postoperative pain control and drug-related adverse events were recorded. Three children who received nalbuphine required an extra bolus dose within the 12 hrs. of post-surgery versus one child in the tramadol group. A similar number of patients in both groups required an increment in the infusion rate within the 72 post-surgery hours. Sedation was observed in 2 children in the nalbuphine group and in 1 child in the tramadol group. Four children presented vomiting with tramadol and two with nalbuphine. Cardiovascular parameters remained within the normal ranges in both groups. In conclusion, the bolus/infusion regimen of tramadol evaluated in this study appears to have better postoperative analgesic efficacy than the bolus/infusion regimen of nalbuphine. These preliminary results require further confirmation by studies with a sample size enough to clearly identify differences in their efficacy as well as in the rate of adverse events secondary to the administration of each of them.

Mesoionic heterocycles derived from 1,3-thiazolium-4-olates (thioisomunchnones) undergo thionation with aryl isothiocyanates to afford the corresponding 4-thiolate derivatives. Here, we document this transformation in detail, giving a crystallographic characterization of the solid-state structures. From the mechanistic viewpoint, the formal thionation process could be consistent with a [2 + 2] reaction of the exocyclic C-O bond of the thioisomunchnone with the C=S double bond of the isothiocyanate moiety, which would be competing with a (3 + 2) process as usual in mesoionic rings. Theoretical computations at the [B3LYP/6-31G(d):PM3] level, in which only bond-forming and bond-breaking reactions and neighboring atoms are treated at the DFT level, do reproduce the experimental results and rule out the expected pathway. Calculations instead suggest the existence of a four-step domino pathway through several polar intermediates that agrees with the electronic nature of the substituents involved. The mechanistic hypothesis has further been corroborated by an experiment with isotopically (13)C-labeled PhNCS that unambiguously shows the way in which the exchange reaction occurs.

Objective: To evaluate the quality of care and improvement opportunities of medically ill depressed patients in a Psychiatric Facility using electronic medical records., Methods: Observational, retrospective study. A literature review was conducted to identify and analyze evidence based quality indicators. We scored the clinical records to estimate the proportion of continuous antidepressant treatment at 12 and 24 weeks, response and remission rates at 8 weeks, the use of clinimetric scales, evidence based psychotherapeutic interventions (cognitive and interpersonal), and the emergence of antidepressant related safety events., Results: Of 100 patients with an average age of 48.7 years, 49 % and 34 % received treatment during 12 and 24 weeks respectively. 50 % had response and 28 % remission at 8 weeks. Use of clinimetric scales was registered in 33 % and psychotherapeutic interventions in 28 % of the interviews. One patient had seizures related to antidepressant use., Conclusions: An increase in the proportion of patients achieving remission and the use of clinimetric scales with psychotherapeutic interventions are improvement opportunities to look for in the care of depressed patients with medical comorbidity.

The use of complementary and alternative medicine (CAM) is prevalent among elderly individuals. While race and ethnicity may influence the choice of CAM, it is uncertain how this influence affects an individual's choice of CAM or conventional medicine. Furthermore, it is unclear whether this choice of CAM or conventional medicine might vary for different medical conditions. A survey of CAM use was performed on a convenience sample of 338 multi-ethnic urban elderly subjects who attended clinic at two large university-affiliated hospitals over 2 years. The survey asked about individual CAM therapies used, and whether subjects would prefer conventional (prescription or over-the-counter) or CAM (herbal or other) treatment for three different medical conditions: colds, insomnia, and back pain. Hispanic ethnicity and female gender were the best predictors of CAM use. Blacks were more likely than whites to utilize CAM. Hispanics were more likely to choose herbal medications to self-treat colds and insomnia than whites or blacks, or low-back pain than whites. More Hispanics chose herbal medications to treat insomnia than over-the-counter or prescription medications.

An unusual thionation strategy of mesoionic compounds with aryl isothiocyanates enables a facile synthesis of 1,3-thiazolium-4-thiolate systems. The mechanistic pathway of such a transformation most likely involves a stepwise 1,3-dipolar cycloaddition, which is supported by theoretical calculations performed with a two-layer hybrid method (B3LYP/6-31G(d):PM3).

A series of chiral imines derived from 1-amino-1-deoxyalditols such as d-glucamine, a rather unexplored raw material from the chiral pool, have been serendipitiously transformed into a novel family of N-acetyl-1,3-oxazolidines by means of an unexpected acetylation. The structure of these substances is supported by spectroscopic and crystallographic data. The acetylates also trigger a complex dynamic transformation, in which an initially configured trans oxazolidine converts into a more stable cis-configured derivative. Both isomers can also exist as rotational conformers (E,Z) as a consequence of the restricted rotation around the N-acetyl bond. The barriers to rotation have been determined by variable-temperature experiments. Overall, this transformation most likely involves the intermediacy of a chiral iminium ion, which has been documented in the synthesis of nitrogen heterocycles, thus explaining the experimental facts.

This article describes the systematic preparation of a novel family of carbohydrate amphiphiles and bolaamphiphiles in which hydrophilic and hydrophobic units are connected via a ureido or bis(ureido) moiety. The sugar core is derived from aminopolyols such as D-glucamine (1), N-methyl-D-glucamine (2), or the sugar-like species tris(hydroxymethyl)aminomethane (3). The O-unprotected derivatives behave as self-organizing nonionic surfactants with good water gelation ability, which can be induced under thermal or ultrasound-driven stimuli. In addition, some derivatives of 1 and 2, and rarely 3 also formed lyotropic liquid crystals with lamellar or hexagonal structures that exhibit low-temperature transitions.

The intermolecular potentials for the NO(X 2Pi)-Kr and NO(A 2Sigma+)-Kr systems have been calculated using highly accurate ab initio calculations. The spin-restricted coupled cluster method for the ground 1 2A' state [NO(X 2Pi)-Kr] and the multireference singles and doubles configuration interaction method for the excited 2 2A' state [NO(A 2Sigma+)-Kr], respectively, were used. The potential energy surfaces (PESs) show two linear wells and one that is almost in the perpendicular position. An analytical representation of the PESs has been constructed for the triatomic systems and used to carry out molecular dynamics (MD) simulations of the NO-doped krypton matrix response after excitation of NO. MD results are shown comparatively for three sets of potentials: (1) anisotropic ab initio potentials [NO molecule direction fixed during the dynamics and considered as a point (its center of mass)], (2) isotropic ab initio potentials (isotropic part in a Legendre polynomial expansion of the PESs), and (3) fitted Kr-NO potentials to the spectroscopic data. An important finding of this work is that the anisotropic and isotropic ab initio potentials calculated for the Kr-NO triatomic system are not suitable for describing the dynamics of structural relaxation upon Rydberg excitation of a NO impurity in the crystal. However, the isotropic ab initio potential in the ground state almost overlaps the published experimental potential, being almost independent of the angle asymmetry. This fact is also manifested in the radial distribution function around NO. However, in the case of the excited state the isotropic ab initio potential differs from the fitted potentials, which indicates that the Kr-NO interaction in the matrix is quite different because of the presence of the surrounding Kr atoms acting on the NO molecule. MD simulations for isotropic potentials reasonably reproduce the experimental observables for the femtosecond response and the bubble size but do not match spectroscopic results. A general overall view of the results suggests that, when the Kr-NO interaction takes place inside the matrix, potentials are rather symmetric and less repulsive than those for the triatomic system.