Impact of hormone therapy side effects on health-related quality of life, distress, and well-being of breast cancer survivors.

To explore the modulatory role of Adjuvant Hormone Therapy (AHT) on health-related quality of life (QoL), subjective well-being and distress prevalence in Breast Cancer (BC) survivors, considering the survival phase. Cross-sectional study with control group. 616 BC survivors participated. Examination of interaction effect between AHT and time since end of primary treatment showed that many of the positive changes observed through the survival phases were experienced exclusively by survivors without AHT. When AHT was not prescribed, longer time elapsed was associated with a decrease in distress prevalence and an improvement in subjective well-being and QoL. It seems there is a turning point around the fifth year after finalization of primary treatment, from which the survivors without AHT significantly improve in several areas and those with AHT do so to a lesser extent. It is expected that the improvement in QoL throughout the different survival phases will have a significant impact on the adherence and maintenance of AHT and, consequently, the likelihood of survival. Thus, AHT side-effects should be routinely assessed by health care providers to gain accurate knowledge that allows improving the QoL of BC survivors.

Novel fluorescent anthracene-bodipy dyads displaying sensitivity to pH and turn-on behaviour towards Cu(ii) ions.

Three bichromophoric compounds containing anthracene and bodipy moieties connected by different spacers have been synthesized and fully characterized. The set of spacers comprises a variety of bridges (short and flexible 1,2-diaminoethane in compound 1a, long and flexible 1,8-diaminooctane in compound 1b and short and rigid piperazine in compound 1c). The new compounds show interchromophoric communication via Electronic Energy Transfer (EET). When anthracene is excited, the energy is efficiently transferred to the bodipy moiety. The emission of the acceptor is partially quenched in dyad 1a but remarkably not in 1b and 1c. In an aqueous environment, the fluorescence of the new compounds display sensitivity to pH (emissive at acidic values and non-emissive at neutral ones), a typical behaviour of photoinduced electron-transfer (PET) probes, but with remarkable differences in the pKa of each compound, attributable to the nature of the linker. Additionally, the behaviour in the presence of several metallic cations (Cu2+, Ni2+, Cd2+, Zn2+) has been studied, and a turn-on response towards Cu2+ in water at neutral pH has been found.

The synthesis of new fluorescent bichromophoric compounds as ratiometric pH probes for intracellular measurements.

Three different bichromophoric compounds (1-3) containing an aminomethyl anthracene moiety linked to a second chromophore (pyrene, 4-nitrobenzo-2-oxa-1,3-diazole (NBD) and dansyl) through a valine-derived pseudopeptidic spacer have been prepared and their fluorescent properties studied. The results obtained show that upon irradiation the photophysical behavior of these probes involves electronic energy transfer from the excited anthracene to the second chromophore and also intramolecular photoinduced electron transfer. The X-ray structure obtained for 3 reveals that the folding associated with the pseudopeptidic spacer favours a close proximity of the two chromophores. The emissive response of 3 is clearly dependent on the pH of the medium, hence this bichromophoric compound was shown to be an excellent ratiometric pH fluorescent sensor. The emission intensity due to the anthracene moiety exhibits a decrease at neutral-basic pH values that is concomitant with an increase in the intensity arising from the dansyl fluorophore. These properties make this compound a good candidate for biological pH sensing as has been confirmed by preliminary studies with RAW 264.7 macrophage cells imaged by means of confocal fluorescence microscopy with an average pH estimation of 5.4-5.8 for acidic organelles.

Meiosis and its deviations in polyploid animals.

We review the different modes of meiosis and its deviations encountered in polyploid animals. Bisexual reproduction involving normal meiosis occurs in some allopolyploid frogs with variable degrees of polyploidy. Aberrant modes of bisexual reproduction include gynogenesis, where a sperm stimulates the egg to develop. The sperm may enter the egg but there is no fertilization and syngamy. In hybridogenesis, a genome is eliminated to produce haploid or diploid eggs or sperm. Ploidy can be elevated by fertilization with a haploid sperm in meiotic hybridogenesis, which elevates the ploidy of hybrid offspring such that they produce diploid gametes. Polyploids are then produced in the next generation. In kleptogenesis, females acquire full or partial genomes from their partners. In pre-equalizing hybrid meiosis, one genome is transmitted in the Mendelian fashion, while the other is transmitted clonally. Parthenogenetic animals have a very wide range of mechanisms for restoring or maintaining the mother's ploidy level, including gamete duplication, terminal fusion, central fusion, fusion of the first polar nucleus with the product of the first division, and premeiotic duplication followed by a normal meiosis. In apomictic parthenogenesis, meiosis is replaced by what is effectively mitotic cell division. The above modes have different evolutionary consequences, which are discussed. See also the sister article by Grandont et al. in this themed issue.

Pathogen inactivation technology applied to a blood component collected from an asymptomatic carrier of Leishmania infantum: a case report.

Asymptomatic Leishmania infections have been the main cause of transfusion transmission in endemic areas. Polymerase chain reaction has been used to detect L. infantum DNA in the peripheral blood of asymptomatic Leishmania carriers. In our region, the prevalence of asymptomatic L. infantum infection in donors is markedly high (5·9% of donors studied). We investigated the ability of pathogen inactivation technology, using amotosalen and UVA illumination, to eliminate L. infantum in a blood component collected from an asymptomatic L. infantum infected donor. This is the first report of the INTERCEPT system being used to eliminate a parasite from a component collected from a donor.

Efficiency and safety of inhaled amphotericin B lipid complex (Abelcet) in the prophylaxis of invasive fungal infections following lung transplantation.

BACKGROUND: Invasive fungal infections (IFIs) in patients undergoing lung transplantation (LT) are associated with significant mortality. Previous studies have shown the efficacy of aerosolized amphotericin B deoxycholate and oral fluconazole for antifungal prophylaxis. Evolving data show a potential advantage of prophylaxis with lipid-based formulations of amphotericin B in the prevention of IFIs. We reviewed the incidence of IFIs among patients receiving aerosolized amphotericin B lipid complex (ABLC) in LT. METHODS: We undertook a retrospective review of the results of our antifungal protocol in a cohort of 60 LT patients. We analyzed the efficiency, safety, and tolerability of 50 mg of aerosolized ABLC administered postoperatively for IFI prophylaxis once every 2 days for 2 weeks and then once per week for at least 13 weeks. In addition, these transplanted patients received fluconazole (200 mg/d) during the first 21 days posttransplant. The prophylaxis-related efficiency and safety were quantified for IFIs and adverse events (AEs) for 6 months after study drug initiation. RESULTS: Prophylaxis was efficient in 59 (98.3%) patients. Only one patient developed a possible IFI, due to Aspergillus fumigatus. Four patients presented nausea and vomiting as an AE, although aerosolized amphotericin B was ongoing. CONCLUSIONS: Nebulized ABLC was effective, safe, and well tolerated for the prophylaxis of aspergillosis in lung transplant patients during the early posttransplant period.

Heritabilities and additive genetic variances of the activities of some enzymes in Drosophila melanogaster populations living in different habitats.

Drosophila melanogaster samples were collected from a large population in two habitats: farmyards and distilleries. Samples were taken from two villages in each habitat. Three isofemale lines were established from all four samples and full-sib crosses were set in each isofemale line. Activities of four enzymes (ADH, alpha GPDH, IDH and 6PGDH) were measured in the offspring of each cross on starch gel after electrophoresis. Broad sense heritabilities and additive genetic variances were estimated in all four samples. Most of the activity variation was observed within the isofemale lines. The isofemale lines tended to be more different in the distilleries than in the farmyards. There was no significant difference in the average activities between the two habitats for any of the enzymes investigated. The additive genetic variance of the enzyme activities did not exhibit a consistent habitat pattern. In the farmyard habitat, we detected a higher activity variation in Tiszafüred than in the other village. Strong correlation was observed among the activities of the enzymes investigated. Correlation coefficients indicated higher level of correlation in the samples collected in Tiszafüred than in those originating from Tiszaszolos. The heritability values were rather high and they had a considerable variation both between the habitats and across the enzymes.

A unique mechanism of nuclear division in Giardia lamblia involves components of the ventral disk and the nuclear envelope

The fine structure of the binucleate, parasitic protist Giardia lamblia during interphase and divisional stages was studied by serial thin sectioning and three-dimensional reconstructions. The earlier sign of nuclear division is the development of a few peripheral areas of densely packed chromatin directly attached to the inner nuclear envelope. An intracytoplasmic sheet of ventral disk components grows from the cell periphery towards one of the nuclei, apparently constricting this nucleus, which becomes located at a ventral bulge. After the basal bodies become duplicated, a full nuclear division occurs in trophozoites, giving two pairs of parent-daughter nuclei. This full division occurs in a dorsal-ventral direction, with the resulting nuclear pairs located at the sides of the two sets of basal bodies. A new ventral disk is formed from the disk-derived sheets in the cell harboring the four nuclei. Cytokinesis is polymorphic, but at early stages is dorsal-to-dorsal. Encysting trophozoites show the development of Golgi cisternae stacks and dense, specific secretory granules. 3-D reconstructions show that cysts contain a single pair of incompletely strangled nuclei. The dividing Giardia lacks a typical, microtubular spindle either inside or outside the nuclei. The nuclear envelope seems to be the only structure involved in the final division of the parent-daughter nuclei.

Evolution of clonality and polyploidy in a weevil system.

The increased interest in asexual organisms calls for in-depth studies of asexual complexes that actively give rise to new clones. We present an extensive molecular study of the Otiorhynchus scaber (Coleoptera, Curculionidae) weevil system. Three forms have traditionally been recognized: diploid sexuals, triploid, and tetraploid parthenogens. All forms coexist in a small central area, but only the polyploid parthenogens have colonized marginal areas. Analyzing the phylogenetic relationship, based on three partial mitochondrial genes, of 95 individuals from 19 populations, we find that parthenogenesis and polyploidy have originated at least three times from different diploid lineages. We observe two major mitochondrial lineages, with over 2.5% sequence divergence between the most basal groups within them, and find that current distribution and phylogenetic relationships are weakly correlated. Quite unexpectedly, we also discover diploid clones that coexist with, and are morphologically indistinguishable from, the diploid sexual females. Our results support that these diploid clones are derived directly from the diploid sexuals. We also find that it is mainly an increase in ploidy level and not the benefits of asexual reproduction that confers to polyploid parthenogens the advantage over their diploid sexual relatives.

Interaction between the Adh and Odh loci in response to ethanol in Drosophila melanogaster.

Six Drosophila melanogaster strains were constructed from two isofemale lines. The strains had four allele combinations at the alcohol dehydrogenase (Adh) and octanol dehydrogenase (Odh) loci, while all alpha-glycerophosphate dehydrogenase (alpha Gpdh), malate dehydrogenase (Mdh), and aldehyde oxidase (Aldox) alleles were identical. Second-instar and early and late third-instar larvae were exposed to different concentrations of ethanol (0, 5, and 7.5%) and 3 days later fresh weights and the activities of ADH, ODH, alpha GPDH, and MDH were measured. Activity differences were observed between the two Adh genotypes: ADHF allozyme had considerably higher activity than ADHS. Exogenous ethanol resulted in the highest increase in ADH activity in the second- and early third-instar stages. This ADH induction depended on the allele combination at the Adh and Odh loci; e.g., in the strain having the AdhS-OdhS allele combination, increased ADH activity was observed only after exposure to 7.5% ethanol. ODH activities differed according to the Odh genotypes, in that the ODHS allozyme had a higher activity than ODHF. ODH activities did not appreciably respond to different ethanol treatments. All six strains had identical alleles at the Mdh and alpha Gpdh loci, but nevertheless, the responses of these enzymes to ethanol depended on the allele combinations at the Adh and Odh loci. alpha GPDH activity followed that of ADH in all experiments. MDH activities were not influenced by exogenous ethanol in the strains homozygous for the AdhS allele. In AdhF strains, however, exposure to 7.5% ethanol resulted in a considerable decrease in MDH activity in the second-instar larvae. Correlations among the response variables showed that ODH activities were strongly associated with fresh weight and the activities of all other enzymes, except for ADH. ADH activity, however, showed a significant correlation only with alpha GPDH activity throughout the larval life. Both MDH and ODH activities were found to be in strong negative correlation with ADH activity in the second-instar larvae. At this most sensitive life stage, the metabolic response to ethanol is highly correlated.

Ultrastructure of regions containing homologous loci in polytene chromosomes of Drosophila melanogaster and Drosophila subobscura.

We have used a new approach involving in situ hybridisation and electron microscopy to establish ultrastructural homologies between polytene chromosome regions of Drosophila melanogaster and Drosophila subobscura. Twelve probes were chosen to cover all the chromosomal elements: the myospheroid gene, the collagen type IV gene, the collagen-like gene, the w26 homeobox gene, the beta3 tubulin gene, the kinesin heavy chain gene, the tryptophan hydrolase gene, the Hsp82, Hsp22-26 and Hsp23-28, Hsp68, Hsp70 genes and the beta unit of the F0-F1 ATPase gene. Most of these loci were previously undescribed in D. subobscura and imprecisely located in D. melanogaster. We have demonstrated here, by an ultrastructural analysis of each chromosomal region, that homologous genetic loci tend to show a similar ultrastructure in the two species. With a few exceptions, the structural homology extends to the chromosomal regions surrounding the loci. In some cases, however, no structurally recognisable homology can be seen either in the locus or in its flanking regions.

Enzymatic responses of Drosophila melanogaster to long- and short-term exposures to ethanol.

The effects of environmental ethanol on larva-to-pupa survival and on the activities of four enzymes were investigated in three Drosophila melanogaster strains. The strains had different allelic combinations at the Odh and Aldox loci on their third chromosomes, but they all carried the Adh(S)-Gpdh(F) allelic combination on the second chromosome. Replicates of each of the strains were exposed to three different ethanol treatments: (i) no ethanol in the medium (control); (ii) 5% ethanol for a single generation (short-term exposure); (iii) 5% ethanol for 20 generations (long-term exposure). In all experiments, the activities of four enzymes (ADH, ODH, GPDH and AOX) were measured in larvae, pupae and adults. The results showed that (i) the larval and adult metabolic responses to environmental ethanol were different; (ii) enzyme activity changes under short-term exposure differed from those measured under long-term exposure; (iii) the activities of the allozymes common to all strains (ADH-S and GPDH-F), differed depending on the genetic background. Changes in larva-to-pupa survival were seen when the larvae of control and exposed lines of the three strains were confronted with various concentrations of ethanol. In all three strains, the exposed lines had significantly higher initial survival rate and ethanol tolerance than the control lines. Strain-specific differences were observed in the ethanol tolerance of both types of line.

Differences in environmental temperature, ethanol and sucrose associated with enzyme activity and weight changes in Drosophila melanogaster.

Activity changes of three enzymes (ADH, ODH and AOX) of Drosophila melanogaster were followed under different environmental conditions. The influences of ethanol, starvation (no carbohydrates in the medium) and ethanol stress during starvation were studied at both 18 and 26 degrees C. Two strains that were monomorphic for different alleles at the Odh and Aldox loci but otherwise identical were used. The investigated environmental conditions affected ADH induction by exogenous ethanol differently in the two strains. The different allozymes of ODH and AOX also responded differently to the treatments. We observed that the sucrose content of the medium on which ethanol exposure took place and the temperature strongly affected the responses within any single strain. Correlations were estimated among the three enzymes in the larval and adult stages of each strain separately. At both temperatures, differences between strains were observed in the patterns of associations of the response variables, in the larval, but not in the adult stages.

Electron micrograph map of the Drosophila melanogaster polytene chromosome 3R divisions 91 through 100.

The banding pattern of the distal half of the polytene salivary gland 3R chromosome of Drosophila melanogaster was studied by means of the thin section electron microscopy. Bands were identified according to the revised light microscopic map of Bridges. Bridges' map contains 332 single bands and 137 double bands within the region 91 through 100. This makes a total of 606 bands when the doublets are counted as two bands each, but 469 bands when the doublets are counted as one band. In the electron micrographs we found a total of 443 bands within this region. 109 Bridges' singlets were easily detected in almost all thin sections, while 144 mainly faint bands could be seen only in some micrographs. 79 Bridges' single bands and one doublet (94D7-8) could not be found. 42 Bridges' doublets were made up of two separate bands each, 87 Bridges' doublets looked single, and three pairs of Bridges' doublets formed dark complexes in the thin sections. The telomere region with the most distal band 100F4-5 was gray. A total of 15 new bands, which are not drawn on Bridges' map, were detected. Most of the new bands were in the divisions 96 and 99.

Electron micrograph map of the Drosophila melanogaster polytene chromosome 3R divisions 81 through 90.

The banding pattern of the proximal half of the polytene salivary gland 3R chromosome of Drosophila melanogaster was studied with thin section electron microscopy. Bands were identified according to Bridges' revised light microscopic map, which contains 330 single and 121 double bands within the regions 81 through 90. We found a total of 447 bands in this region. 97 Bridges' single bands were easily detected in almost all thin sections, while 177 faint bands could be seen only in some micrographs. 56 Bridges' single bands could not be found. 32 Bridges' doublets were made up of two separate bands each in thin sections. The other 89 Bridges' doublets seemed to be either single bands or remained obscure. A total of 20 small new bands, which were not drawn on Bridges' map, were detected.

Does Drosophila melanogaster use ethanol as an energy source during starvation?

The influence of starvation on activities of three enzymes (ADH, ODH and alpha GPDH) was studied in Drosophila melanogaster. The changes were compared in two inbred lines which had different allelic combinations at the Odh and Aldox loci. We also studied the effect of ethanol on media which contained no sucrose ("starvation conditions"). The results show that there are large differences in the larval and adult alcohol utilization. The alcohol content of the medium, in the absence of sugar, appeared to be toxic for the larvae, while the adults appeared to utilize it as an energy source. The two strains differed little in their responses to starvation or to the ethanol treatment applied under starvation conditions. We conclude that the degree of toxicity of ethanol is highly dependent on the presence of sucrose.

The influence of the Odh-Aldox region of the third chromosome on the response of Drosophila melanogaster to environmental alcohol.

Second instar larvae of Drosophila melanogaster were exposed to exogenous alcohol, which is known to influence the activities of several enzymes. In this study, the activity changes were followed in four enzymes (ADH, ODH, alpha GPDH and AOX) during ethanol exposure and compared in three inbred lines that had different allelic combinations at the Odh and Aldox loci. The results indicate that the Odh-Aldox region of the third chromosome may alter the general response to ethanol. The activity of ADH increased considerably in two strains in the larval stages in the presence of alcohol; nevertheless, strain 1, with the OdhS-AldoxF allelic combination, showed a delay in the ADH induction compared to strain 2, which had the OdhF-AldoxS combination. In strain 3 (OdhS*-AldoxS) larvae, ADH induction by environmental ethanol was not detected. Moreover, the activities of alpha GPDH and AOX in strains 2 and 3 were not affected by ethanol. In contrast, the activities of all four enzymes in strain 1 changed after exposure to ethanol.

Electron microscopic analysis of the banding pattern in the salivary gland chromosomes of Drosophila melanogaster. Divisions 11 through 20 of X.

The banding pattern of the proximal half of the polytene salivary gland X chromosome of Drosophila melanogaster was studied using thin section electron microscopy. The bands were identified according to Bridges' revised light microscopic map. On Bridges' map, the divisions 11 to 20 contain 112 single bands and as many as 181 double bands. A majority of Bridges' single bands were identified in the thin sections. A total of 23 Bridges' single bands (and 4 bands of division 20) could not be found; in particular, bands were missing from the difficult regions 11DE, 15A, 15C and 16A. Electron microscopy showed the existence of 18 additional faint bands, 4 at the region 18D and 7 at 19EF. Bridges' faintest single bands and the new bands were best seen in formaldehyde fixed material. About 1/4 of Bridges' double bands were found to be made up of two separate bands each. The remaining Bridges' doublets include all kinds of bands: broad, narrow, dark, faint, puffed. Many of them look single in thin sections.