Evaluation of a battery of biotests to improve waste ecotoxicity assessment (HP 14), using incineration bottom ash as a case study.

The assessment of waste ecotoxicity (hazardous property HP14 in the European Union) is fundamental for proper waste classification and safe application/disposal. Biotests are relevant for evaluating waste complex matrices, but their efficiency is crucial to encourage their adoption at the industrial level. This work aims at evaluating possibilities of improving the efficiency of a biotest battery previously suggested in the literature, regarding test selection, duration, and/or laboratory resources optimization. Fresh incineration bottom ash (IBA) was the case study. The test battery analysed included standard aquatic (bacteria, microalgae, macrophytes, daphnids, rotifers, fairy shrimp) and terrestrial (bacteria, plants, earthworms, collembolans) organisms. The assessment followed an Extended Limit Test design (three dilutions of eluate or solid IBA) and the Lowest Ineffective Dilution (LID-approach) for ecotoxicity classification. The results emphasize the importance of testing different species. It was also evidenced that tests with daphnids and earthworms may be shortened to 24 h; the miniaturization of tests is suitable as e.g. differential sensitivity of microalgae and macrophytes was captured with low variability; alternative testing kits can be used when methodological difficulties are found. Microalgae were more sensitive than macrophytes. Similar results were found for the Thamnotoxkit and daphnids test for eluates with natural pH, so the former may be used as an alternative. B. rapa was the most sensitive organism, suggesting that it may be tested as the only terrestrial plant species and that minimum test duration is appropriate. F. candida does not appear to add information to the battery. The differences in sensitivity of A. fischeri and E. fetida compared to the remaining species were not significant enough to exclude them from the battery. Thus, this work suggests a biotest battery to test IBA comprising aquatic tests - Aliivibrio fischeri, Raphidocelis subcapitata (miniaturised test), and Daphnia magna (24 h when clear deleterious effects are observed) or Thamnocephalus platyurus (toxkit) - and terrestrial tests - Arthrobacter globiformis, Brassica rapa (14 d), and Eisenia fetida (24 h). Testing waste with natural pH is also recommended. The Extended Limit Test design considering the LID-approach seems useful in waste testing, particularly for the industry, involving low effort, test material requirements, and few laboratory resources. The LID-approach allowed for differentiating ecotoxic from non-ecotoxic effects and captured different sensitivities between species. Ecotoxicological assessment of other waste may benefit from these recommendations, but caution should be taken given the properties of each waste type.

Caenorhabditis elegans as a tool for environmental risk assessment: emerging and promising applications for a "nobelized worm".

Caenorhabditis elegans has been an invaluable model organism in research fields such as developmental biology and neurobiology. Neurotoxicity is one of the subfields greatly profiting from the C. elegans model within biomedical context, while the corresponding potential of the organism applied to environmental studies is relevant but has been largely underexplored. Within the biomedical scope, the implication of metals and organic chemicals with pesticide activity (hereinafter designated as pesticides) in the etiology of several neurodegenerative diseases has been extensively investigated using this nematode as a primary model organism. Additionally, as a well-known experimental model bearing high sensitivity to different contaminants and representing important functional levels in soil and aquatic ecosystems, C. elegans has high potential to be extensively integrated within Environmental Risk Assessment (ERA) routines. In spite of the recognition of some regulatory agencies, this actual step has yet to be made. The purpose of this review is to discuss the major advantages supporting the inclusion of C. elegans in lower tiers of ERA. Special emphasis was given to its sensitivity to metals and pesticides, which is similar to that of other model organisms commonly used in ERA (e.g. Daphnia magna and Eisenia sp.), and to the large array of endpoints that can be tested with the species, both concerning the aquatic and the soil compartments. The inclusion of C. elegans testing may hence represent a relevant advance in ERA, providing ecologically relevant insights toward improvement of the regulatory capacity for establishing appropriate environmental protection benchmarks.

Adaptability and stability of soybean cultivars for grain yield and seed quality.

This study aimed at verifying the adaptability and stability of soybean cultivars, considering the grain yield and quality of seeds, adopting univariate and multivariate approaches. The experiments were conducted in two crops, three environments, in 2013/2014 and 2014/2015 crop seasons, in the county of Inconfidentes, Lavras, and Patos de Minas, in the Minas Gerais State, Brazil. We evaluated 17 commercial soybean cultivars. For adaptability and stability evaluations, the Graphic and GGE biplot methods were employed. Previously, a selection index was estimated based on the sum of the standardized variables (Z index). The data relative to grain yield, mass of one thousand grain, uniformity test (sieve retention), and germination test were standardized (Zij) per cultivar. With the sum of Zij, we obtained the selection index for the four traits evaluated together. In the Graphic method evaluation, cultivars NA 7200 RR and CD 2737 RR presented the highest values for selection index Z. By the GGE biplot method, we verified that cultivar NA 7200 RR presented greater stability in both univariate evaluations, for grain yield, and for selection index Z.

Selection of maize inbred lines and gene expression for resistance to ear rot.

In recent years, there has been a large incidence of fungi causing "ear rot" in maize in Brazil, the main fungus being Fusarium verticillioides. The most efficient and competitive alternative for control of this disease consists of using maize hybrids resistant to this pathogen. Thus, the aims of this study were to analyze the genetic variability of maize inbred lines in regard to resistance to ear rot to observe if there is a maternal effect to resistance to ear rot, to study genetic control of the traits evaluated in hybrids originating from inbred lines of the maize breeding program at the Agriculture Department of Universidade Federal de Lavras (Lavras, MG, Brazil), and characterize the gene expression pattern related to the plant defense mechanism against F. verticillioides. High genetic availability was observed for resistance to this disease among the inbred lines evaluated. Considering combined diallel analysis, it was observed that the mean square of general combining ability (GCA) was not significant for the characteristic under study. However, specific combining ability (SCA) was significant, which indicates the predominance of non-additive effects involved in control of the characteristic for the population evaluated. A maternal effect was not observed for the characteristic of ear rot resistance in this study. Inbred lines 22, 58, and 91 showed potential for use in breeding programs aiming at resistance to F. verticillioides. Only two genes, LOX8 and Hsp82, had a satisfactory result that was able to be related to a plant defense mechanism when there is ear rot infection, though expression of these genes was observed in only one susceptible genotype. Thus, the genes LOX8 and Hsp82 are potential molecular markers for selection of maize inbred lines resistant to F. verticillioides.

Effect of bariatric surgery on microvascular dysfunction associated to metabolic syndrome: a 12-month prospective study.

OBJECTIVE: To prospectively evaluate the effect of weight loss after bariatric surgery on microvascular function in morbidly obese patients with and without metabolic syndrome (MetS). METHODS: A cohort of morbidly obese patients with and without MetS was studied before surgery and after 12 months of surgery. Healthy lean controls were also examined. Microvascular function was assessed by postocclusive reactive hyperemia (PORH) at forearm skin evaluated by laser Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated from laser-Doppler skin blood flow and blood pressure. Regression analysis was performed to assess the contribution of different clinical, metabolic and biochemical parameters to microvascular function. RESULTS: Before surgery, 62 obese patients, 39 with MetS and 23 without MetS, and 30 lean control subjects were analyzed. The absolute area under the hyperemic curve (AUC(H)) CVC of PORH was significantly decreased in obese patients compared with lean control subjects. One year after surgery, AUC(H) CVC significantly increased in patients free of MetS, including patients that had MetS before surgery. In contrast, AUC(H) CVC did not significantly change in patients in whom MetS persisted after surgery. Stepwise multivariate regression analysis showed that only changes in HDL cholesterol (HDL-C) and oxidized LDL (oxLDL) independently predicted improvement of AUC(H) after surgery. These two variables together accounted for 40.9% of the variability of change in AUC(H) CVC after surgery. CONCLUSIONS: Bariatric surgery could significantly improve microvascular dysfunction in obese patients, but only in patients free of MetS after surgery. Improvement of microvascular dysfunction is strictly associated to postoperative increase in HDL-C levels and decrease in oxLDL levels.

An integrated characterisation of incineration bottom ashes towards sustainable application: Physicochemical, ecotoxicological, and mechanical properties.

Environmental protection is a central concern regarding municipal solid waste incineration bottom ash (IBA) management, but the assessment of waste Hazardous Property HP14 (ecotoxicity) is still under debate. Civil engineering applications may be a suitable management strategy. This work aimed at evaluating IBA regarding mechanical behaviour and environmental hazardous potential, including a biotest battery for ecotoxicity assessment (comprising miniaturised tests), to explore its potential for safe utilization. Physical, chemical, ecotoxicological (Aliivibrio fischeri, Raphidocelis subcapitata, Lemna minor, Daphnia magna, Lepidium sativum), and mechanical (one-dimensional compressibility, shear strength) analyses were performed. The low leaching for potentially toxic metals and ions complied with European Union (EU) limit values for non-hazardous waste landfills. No relevant ecotoxicological effects were found. The biotest battery seems suitable for ecotoxicological assessment in the aquatic ecosystem, providing wide information on waste impact on different trophic/functional levels and chemical uptake routes, simultaneously involving short-duration tests and reduced amounts of waste. IBA presented more compressibility than sand, but its mixture with sand (30%:70%) was closer to sand compressibility. IBA (lower stresses) and the mixture (higher stresses) showed slightly higher shear strength than sand. Overall, IBA presented the potential for valorisation as loose aggregates from an environmental and mechanical viewpoint in a circular economy framework.

Evaluation of the efficacy of a 2-step etch-and-rinse, 2-step self-etch and 1-step self-etch adhesive systems, in class II primary molars restorations. An one year prospective, randomized clinical trial.

PURPOSE: To evaluate the clinical efficacy at 6 months (6 M) and 12 months (12 M) of 3 adhesive strategies (two-step etch-and-rinse; two-step self-etch; one step self-etch) used in composite resin restorations in primary molars. METHODS: This randomized clinical study involved 101 class II restorations in primary molars of 34 children (4-8 years old), distributed by 3 groups according to the 3 tested adhesive systems: GI- ClearfilTMS3Bond Plus (CSB); GII- ClearfilTMSE Protect Bond (CSEPB); GIII- Prime&Bond®XP (PBXP). Restorations were evaluated according to FDI criteria, immediately after execution, at 6 M and 12 M. All ethical and legal requirements were met. Statistical analysis was performed using IBM®SPSS®v26 and MS Excel® (5% significance level). RESULTS: The aesthetic, biological and most of the functional parameters evaluated remained without significant changes over time. Statistically significant differences were only found regarding the "marginal adaptation" parameter at 12 M, with worsening of scores for the three groups (p < 0.001). Comparing the groups, no significant differences were detected between any of the evaluated parameters (aesthetics properties: p = 0.721; functional properties: p = 0.122). CONCLUSIONS: After a one-year period, the self-etch adhesives tested presented a clinical efficacy similar to the etch-and-rinse adhesive in restoring class II cavities in primary molars. TRIAL REGISTRATION NUMBER: ISRCTN11458186.

The role of mitochondrial DNA damage in the citotoxicity of reactive oxygen species.

Mitochondria contain their own genome, a small circular molecule of around 16.5 kbases. The mitochondrial DNA (mtDNA) encodes for only 13 polypeptides, but its integrity is essential for mitochondrial function, as all 13 proteins are regulatory subunits of the oxidative phosphorylation complexes. Nonetheless, the mtDNA is physically associated with the inner mitochondrial membrane, where the majority of the cellular reactive oxygen species are generated. In fact, the mitochondrial DNA accumulates high levels of oxidized lesions, which have been associated with several pathological and degenerative processes. The cellular responses to nuclear DNA damage have been extensively studied, but so far little is known about the functional outcome and cellular responses to mtDNA damage. In this review we will discuss the mechanisms that lead to damage accumulation and the in vitro models we are establishing to dissect the cellular responses to oxidative damage in the mtDNA and to sort out the differential cellular consequences of accumulation of damage in each cellular genome, the nuclear and the mitochondrial genome.

Prevalence and sociobehavioural determinants of early childhood caries among 5-year-old Portuguese children: a longitudinal study.

PURPOSE: To assess the prevalence of early childhood caries (ECC) and associated factors among a 5-year-old cohort. METHODS: An observational longitudinal study was conducted with a sample of 142 preschoolers. A calibrated dentist performed intraoral examinations following International Caries Detection and Assessment System (ICDAS-II) criteria at baseline and after 6 months. A questionnaire on sociodemographic variables and oral health-related behaviours was answered by caregivers. Statistical analysis included descriptive statistics and computation of confidence intervals (95% confidence level). RESULTS: Baseline prevalence of ECC and severe ECC (S-ECC) were 40.1% and 11.3%, respectively. After 6 months ECC and S-ECC prevalence rates were 46.5%, and 13.2%, respectively. At both evaluations most caries lesions were untreated. Parental education and occupation were significantly associated with ECC. Behaviour variables found to be significantly associated with the disease comprised: establishing toothbrushing habits before the first year, toothbrushing twice daily and with parental assistance, frequency of dental visits, age at first dental visits, daily ingestion of sweets and number of daily meals. CONCLUSION: The prevalence of ECC was very high, with most of the lesions left untreated. ECC experience was associated with participants' socioeconomic background and several of the surveyed oral health-related behaviour variables.

Assessing the neurotoxicity of the carbamate methomyl in Caenorhabditis elegans with a multi-level approach.

The neurotoxicity and developmental effects of a widely applied insecticide (methomyl) was investigated by a multi-level approach (behavior and biometry, biochemical alterations and neurodegeneration) in Caenorhabditis elegans upon a short-term exposure (1 h) and a post-exposure period (48 h). The 1-h exposure to sub-lethal concentrations of methomyl (lower than 0.320 g L-1; i.e. below the estimated LC10) triggered significant changes on motor behavior and development impairment. The type of movement was significantly altered in methomyl-exposed worms, as well as biometric parameters (worms frequently idle and moving more backwards than controls; small body area, length and wavelength). These effects were followed by an increase of acetylcholine levels. Interestingly, after the 48-h recovery period, movement of previously exposed worms was similar to controls, and a concentration-dependent reversion of biometric endpoints was recorded, pointing out the transient action of the carbamate in line with an apparent absence of cholinergic neurons damage. This study provided new insight on the neurotoxicity of methomyl by showing that effects on movement and development were transient, and apparently did not result in neurodegeneration in cholinergic neurons. Moreover, these findings reinforced the advantages of using C. elegans in a multi-level approach for pesticide effects assessment.

Influence of crop management practices on bean foliage arthropods.

Crop management practices can affect the population of phytophagous pest species and beneficial arthropods with consequences for integrated pest management. In this study, we determined the effect of no-tillage and crop residue management on the arthropod community associated with the canopy of common beans (Phaseolus vulgaris L.). Abundance and species composition of herbivorous, detritivorous, predaceous and parasitoid arthropods were recorded during the growing seasons of 2003 and 2004 in Coimbra County, Minas Gerais State, Brazil. Arthropod diversity and guild composition were similar among crop management systems, but their abundance was higher under no-tillage relative to conventional cultivation and where residues from the preceding crop were maintained in the field. Thirty-four arthropod species were recorded, and those most representative of the impact of the crop management practices were Hypogastrura springtails, Empoasca kraemeri and Circulifer leafhoppers, and Solenopsis ants. The infestation levels of major insect-pests, especially leafhoppers (Hemiptera: Cicadellidae), was on average seven-fold lower under no-tillage with retention of crop residues relative to the conventional system with removal of residues, whereas the abundance of predatory ants (Hymenoptera: Formicidae) and springtails (Collembola: Hypogastruridae) were, respectively, about seven- and 15-fold higher in that treatment. Importantly, a significant trophic interaction among crop residues, detritivores, predators and herbivores was observed. Plots managed with no-tillage and retention of crop residues had the highest bean yield, while those with conventional cultivation and removal of the crop residues yielded significantly less beans. This research shows that cropping systems that include zero tillage and crop residue retention can reduce infestation by foliar insect-pests and increase abundance of predators and detritivores, thus having direct consequences for insect pest management.

Environmental benchmarks based on ecotoxicological assessment with planktonic species might not adequately protect benthic assemblages in lotic systems.

Freshwater ecosystems face widespread diffuse and point-source contamination. Species Sensitivity Distributions (SSDs) have been used as a tool to determine chemical concentration benchmarks that represent protective levels for most species in the environment. Here we used a SSD approach to assess on the adequacy of standard planktonic organisms to reflect the response of benthic communities, critically supporting the structure and function of lotic ecosystems. For the purpose, SSDs reflecting non-lethal responses of standard planktonic and selected benthic organisms were built based on EC50 values (collected in the literature or estimated following testing herein) regarding three model contaminants: potassium dichromate (PD), 3,5-dichlorophenol (DCP) and lead chloride (LC). The derived HC5 estimates were discriminatory between chemicals and the uncertainty associated with the estimate was remarkably low. The HC5 estimates with corresponding uncertainty were generally within the same order of magnitude for the three chemicals tested, with better discrimination between chemicals regarding their hazardous potential being achieved for benthic organisms: DCP was clearly less hazardous than PD, but LC tends to be as hazardous as PD and DCP (assuming the confidence interval ranges). Moreover, benthic communities were more sensitive to both DCP and PD, in this later case the HC5 being lower by more than one order of magnitude than that found for planktonic communities; for LC, confidence intervals overlapped, preventing a feasible assumption regarding differential sensitivity of the compared communities. Microphytobenthos was highlighted as the most sensitive group to the three tested chemicals in SSDs covering the benthic compartment, while SSDs with planktonic organisms did not consistently show trends in sensitivity ordering. Overall, our results suggest that protective benchmarks retrieved from SSDs built with the responses of standard planktonic organisms (which are the most commonly used for regulation purposes) do not adequately protect benthic communities.

Cytotoxicity profiling of deep eutectic solvents to human skin cells.

The tailor-made character of deep eutectic solvents (DES) turns them very attractive to be used in several applications, including in health-related areas such as pharmaceutical, nutraceutical, and cosmetic industries. However, although DES has been touted as "green" solvents, several works proved that their potential toxicity should not be neglected. Using the premise of DES applicability in the cosmetic and pharmaceutical sectors, we chose two cell lines to work as a skin model (keratinocytes HaCaT and tumor melanocytes MNT-1), to assess DES cytotoxicity. The effect of three different hydrogen bond acceptors (HBA) ([Chol]Cl, [N1111]Cl and [N4444]Cl) and three different hydrogen bond donors (HBD) (hexanoic and butanoic acid, ethylene glycol, 1-propanol and urea) were evaluated through a common viability assay (MTT assay). Results were promising since [Chol]Cl and [N1111]Cl- based DES showed good biocompatibility for the tested cells. [N4444]Cl-based DES, however, showed cytotoxicity for both cell lines, with the HBA being the driver of the toxicity. Interestingly, some compounds increased cell viability in the HaCaT cell line, namely [Chol]Cl, ethylene glycol, hexanoic acid, urea, and all [Chol]Cl and [N1111]Cl-based DES and should be considered as targets for future studies. These results highlight their possible use in cosmetic or pharmaceutical formulations.

[Competencies in palliative care: what should the physicians be able to do?]. / Compétences en soins patiatifs: que faut-il savoir faire en tant que médecin?

Palliative patients (patients with progressive incurable illnesses) have a number of needs, early and late in their illness trajectories. This article highlights some of the most important competencies required by physicians to address these needs. They cover a broad spectrum of domains and include pain and symptom management, communication, disclosure, prognostication, and psychological, social and spiritual needs. All physicians, generalists and specialists alike, should possess the basic competencies but should also recognize that some patients, especially those not responding to initial strategies, require timely referrals to specialized palliative care teams.

One living donor and two donations: sequential kidney and liver donation with 20-years interval.

The shortage of cadaveric donor organs remains the critical factor limiting the use of organ transplantation. In this environment of organ shortage, living donor transplantation has emerged as a reasonable therapeutic alternative. Simultaneous kidney-liver transplantation from the same donor has been described. We report a case of right liver lobe transplant from a living donor who had donated his kidney to the same recipient 20 years prior.

Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study.

CONTEXT: Delirium impedes communication and contributes to symptom distress in patients with advanced cancer. There are few prospective data on the reversal of delirium in this population. OBJECTIVES: To evaluate the occurrence, precipitating factors, and reversibility of delirium in patients with advanced cancer. DESIGN: Prospective serial assessment in a consecutive cohort of 113 patients with advanced cancer. Precipitating factors were examined using standardized criteria; 104 patients met eligibility criteria. SETTING: Acute palliative care unit in a university-affiliated teaching hospital. MAIN OUTCOME MEASURES: Delirium occurrence and reversal rates, duration, and patient survival. Strengths of association of various precipitating factors with reversal were expressed as hazard ratios (HRs) in univariate and multivariate analyses. RESULTS: On admission, delirium was diagnosed in 44 patients (42%), and of the remaining 60, delirium developed in 27 (45%). Reversal of delirium occurred in 46 (49%) of 94 episodes in 71 patients. Terminal delirium occurred in 46 (88%) of the 52 deaths. In univariate analysis, psychoactive medications, predominantly opioids (HR, 8.85; 95% confidence interval [CI], 2.13-36.74), and dehydration (HR, 2.35; 95% CI, 1.20-4.62) were associated with reversibility. Hypoxic encephalopathy (HR, 0.39; 95% CI, 0.19-0.80) and metabolic factors (HR, 0.44; 95% CI, 0.21-0.91) were associated with nonreversibility. In mulitivariate analysis, psychoactive medications (HR, 6.65; 95% CI, 1.49-29.62), hypoxic encephalopathy (HR, 0.32; 95% CI, 0.15-0.70), and nonrespiratory infection (HR, 0.23; 95% CI, 0.08-0.64) had independent associations. Patients with delirium had poorer survival rates than controls (P<.001). CONCLUSIONS: Delirium is a frequent, multifactorial complication in advanced cancer. Despite its terminal presentation in most patients, delirium is reversible in approximately 50% of episodes. Delirium precipitated by opioids and other psychoactive medications and dehydration is frequently reversible with change of opioid or dose reduction, discontinuation of unnecessary psychoactive medication, or hydration, respectively.

Internet usage among women with breast cancer: an exploratory study.

An increasing number of breast cancer patients are accessing the Internet for medical information. A survey was administered to breast cancer patients and their families attending follow-up outpatient clinics in a comprehensive cancer care center to explore their frequency of Internet use, their motivation for online activity, the type of information they sought, and the perceived impact of the information they found on the Internet on their medical care. The survey was conducted over a 4-month period. A total of 107 surveys were returned. Seventy-nine of these (74%) were from patients while 28 (26%) were from family members and friends. Thirty-four of the patient responses (43%) indicated that the patient had used the Internet to look for cancer-related information. Patients who had used the Internet to access cancer-related information were significantly younger (P = 0.007), better educated (P = 0.027), and less satisfied with the amount of treatment-related information given by caregivers than those patients who had not used the Internet to access cancer-related information (P = 0.032). The majority of patient Internet users desired more information on their cancer and its treatment (91%), looked up information that was presented to them by their clinicians (66%), researched other treatment options (63%), and obtained more information on "alternative treatments" (63%). Patient Internet users generally found the cancer-related information on the Internet to be useful, and the majority discussed Internet-derived information with their health care providers and perceived that clinicians listened to such information. However, 53% were undecided about the trustworthiness of the medical information obtained via the Internet. Internet nonusers commonly lacked Internet access (53%) or were unfamiliar with the Internet (33%), but few (13%) distrusted Internet-derived information. This exploratory study underscores the need for more research in this area, specifically with the aims of identifying and verifying factors that lead patients to use the Internet and the impact of their online activities on their medical care.

Esophageal obstruction by solidification of the enteral feed: a complication to be prevented.

We report three cases of esophageal obstruction due to solidification of enteral feed refluxed from the stomach in patients being fed through a nasogastric tube. All three patients were administered sucralfate continuously by tube. The few previous descriptions of this rare complication have also implicated sucralfate with its pathogenesis. Given its clinical importance and the growing use of long-term enteral nutrition, this adverse event needs to be considered.

Synthesis and Conformational Characteristics of Inherently Chiral Monoalkyl Ethers of p-tert-Butyldihomooxacalix[4]arene.

The synthesis of four inherently chiral monoalkyl ethers (methyl, ethyl, allyl, and benzyl), derived from p-tert-butyldihomooxacalix[4]arene, is described. Their conformational features were studied by variable temperature (1)H NMR spectroscopy in solvents with different polarity, such as chloroform (or CDCl(2)CDCl(2)), acetone, DMSO, and pyridine. Coalescence temperatures and DeltaG() were determined in CDCl(2)CDCl(2) and pyridine solutions. Monomethyl ether has a T(c) of 86 degrees C in CDCl(2)CDCl(2) and of -8 degrees C in pyridine, and the other derivatives are conformationally immobilized (DeltaG() >> 20 kcal mol(-1) in both solvents). The cone conformation, obtained for all monoethers, was confirmed by (13)C and NOESY spectra and also from a series of NOE 1D experiments. Complete assignment of both proton and carbon NMR spectra was achieved for the monomethyl ether by a combination of COSY, HMQC, and selective INEPT experiments, in chloroform at room temperature. Inherent chirality for all compounds was demonstrated by the addition of Pirkle's reagent to CDCl(3) solutions of monoethers derivatives, causing duplication of the NMR proton signals.

The impact of delirium on the circadian distribution of breakthrough analgesia in advanced cancer patients.

Most cancer patients will experience pain requiring opioid therapy during their illness. Standard opioid therapy includes fixed scheduled doses and so-called "rescue" doses for breakthrough pain. Circadian rhythms seem to influence the expression of pain and the responsiveness to analgesic medication. Delirium is a common complication in advanced cancer patients and it also may modify the expression of pain and the use of analgesic medication. We reviewed the circadian distribution of breakthrough analgesia (BTA) doses in 104 advanced cancer patients who were part of a prospective study of the occurrence of delirium. We found that the circadian distribution of BTA is significantly different from a random distribution in the case of patients with and without delirium. Patients without delirium tended to use more BTA (P < 0.001) in the morning, whereas patients with delirium tended to use more BTA in the evening and at night (P = 0.02). We conclude that delirium is associated with changes in the circadian distribution of BTA, which is possibly related to reversal of the normal circadian rhythm.