The silent transition from curative to palliative treatment: a qualitative study about cancer patients' perceptions of end-of-life discussions with oncologists.

OBJECTIVE: The aims of the study were to examine patients' experiences of end-of-life (EOL) discussions and to shed light on patients' perceptions of the transition from curative to palliative care. METHODS: This study was based on a qualitative methodology; we conducted semi-structured interviews with advanced cancer patients admitted to the palliative care unit (PCU) of the Medical University of Vienna. Interviews were recorded digitally and transcribed verbatim. Data were analyzed based on thematic analysis, using the MAXQDA software. RESULTS: Twelve interviews were conducted with patients living with terminal cancer who were no longer under curative treatment. The findings revealed three themes: (1) that the medical EOL conversation contributed to the transition process from curative to palliative care, (2) that patients' information preferences were ambivalent and modulated by defense mechanisms, and (3) that the realization and integration of medical EOL conversations into the individual's personal frame of reference is a process that needs effort and information from different sources coming together. CONCLUSIONS: The results of the present study offer insight into how patients experienced their transition from curative to palliative care and into how EOL discussions are only one element within the disease trajectory. Many patients struggle with their situations. Therefore, more emphasis should be put on repeated offers to have EOL conversations and on early integration of aspects of palliative care into the overall treatment.

Regorafenib therapy in metastatic colorectal cancer patients: markers and outcome in an actual clinical setting.

The oral multikinase inhibitor regorafenib had beneficial effects in randomized clinical phase III trials compared to the placebo in patients with metastatic colorectal cancer (mCRC) who progressed on standard therapies. The factors which influence regorafenib response and therapy sequence during treatment history are still highly discussed, and herein we analyzed the therapy algorithm, outcome and clinical markers following regorafenib application in a single center register study. Clinical data for 48 metastatic colorectal cancer patients were collected from 01.01.2013 to 31.12.2016. Treatment effects according to various patient and tumor characteristics were evaluated using univariate and multivariate Cox proportional hazard regression models. The 48 patients comprised 14 (29%) females and 34 (71%) males, with mean age 64.2±9 and ECOG 0-1. Progression free survival under regorafenib therapy was 2.9 months (quartiles 2.2; 4.4) and the overall response rate was 2 (4%) and disease control rate was 19 (40%). Overall survival (OS) and progression free survival (PFS) were investigated under regorafenib in the chemotherapy regimen given immediately before and afterthis treatment. Variables including tumor localization, Ras status, CEA and CA 19-9 plasma levels were analyzed for their impact on PFS, and the regorafenib-related adverse events were also observed. Our study confirms the efficacy of regorafenib in a real-life setting. We established that response rate and PFS in regorafenib treatment are independent of tumor localization, Ras status or biomarkers such as CEA and CA 19-9. Trifluridin/tripacil application or re-induction of chemotherapy +/- target therapy was effective following regorafenib therapy.

The mitochondrial genome of Arabidopsis thaliana contains 57 genes in 366,924 nucleotides.

We have determined the complete sequence of the mitochondrial DNA in the model plant species Arabidopsis thaliana, affording access to the first of its three genomes. The 366,924 nucleotides code for 57 identified genes, which cover only 10% of the genome. Introns in these genes add about 8%, open reading frames larger than 100 amino acids represent 10% of the genome, duplications account for 7%, remnants of retrotransposons of nuclear origin contribute 4% and integrated plastid sequences amount to 1%-leaving 60% of the genome unaccounted for. With the significant contribution of duplications, imported foreign DNA and the extensive background of apparently functionless sequences, the mosaic structure of the Arabidopsis thaliana mitochondrial genome features many aspects of size-relaxed nuclear genomes.

Prevalence of anxiety and depression in people with different types of cancer or haematologic malignancies: a cross-sectional study.

AIMS: Cancer patients often present with psychological symptoms that affect their quality of life, physical health outcomes and survival. Two of the most frequent psychiatric comorbidities are anxiety and depression. However, the prevalence of these disorders among cancer patients remains unclear, as studies frequently report varying rates. In the present study, we aimed to provide robust point estimates for the prevalence of anxiety and depression for both a mixed cancer sample and for 13 cancer types separately, considering confounding variables. METHODS: In a sample of 7509 cancer outpatients (51.4% female), we used the Hospital Anxiety and Depression Scale to assess rates of anxiety and depression. Applying ordinal logistic regression models, we compared the prevalence of anxiety and depression between different cancer types, controlling for age and gender. RESULTS: About one third of our sample showed symptoms of anxiety (35.2%) or depression (27.9%), and every sixth patient had a very likely psychiatric condition, with women being more frequently affected. Elderly patients more often showed signs of depression. The prevalence of anxiety and depression was significantly higher in lung and brain cancer patients, than in other cancer patients. Lowest depression rates were found in breast cancer patients. CONCLUSIONS: The prevalence of anxiety and depression is high in cancer patients. Type of cancer is an important predictor for anxiety and depressive symptoms, with lung and brain cancer patients being highly burdened. Considering a personalised medicine approach, physicians should take into account the high prevalence of psychiatric comorbidities and include psychiatric consultations in the treatment plan.

copia-, gypsy- and LINE-like retrotransposon fragments in the mitochondrial genome of Arabidopsis thaliana.

Several retrotransposon fragments are integrated in the mitochondrial genome of Arabidopsis thaliana. These insertions are derived from all three classes of nuclear retrotransposons, the Ty1/copia-, Ty3/gypsy- and non-LTR/LINE-families. Members of the Ty3/gypsy group of elements have not yet been identified in the nuclear genome of Arabidopsis. The varying degrees of similarity with nuclear elements and the dispersed locations of the sequences in the mitochondrial genome suggest numerous independent transfer-insertion events in the evolutionary history of this plant mitochondrial genome. Overall, we estimate remnants of retrotransposons to cover > or = 5% of the mitochondrial genome in Arabidopsis.

PTEN expression in endothelial cells is down-regulated by uPAR to promote angiogenesis.

The tumour suppressor phosphatase and tensin homologue (PTEN), mutated or lost in many human cancers, is a major regulator of angiogenesis. However, the cellular mechanism of PTEN regulation in endothelial cells so far remains elusive. Here, we characterise the urokinase receptor (uPAR, CD87) and its tumour-derived soluble form, suPAR, as a key molecule of regulating PTEN in endothelial cells. We observed uPAR-deficient endothelial cells to express enhanced PTEN mRNA- and protein levels. Consistently, uPAR expression in endogenous negative uPAR cells, down-regulated PTEN and activated the PI3K/Akt pathway. Additionally, we found that integrin adhesion receptors act as trans-membrane signaling partners for uPAR to repress PTEN transcription in a NF-κB-dependent manner. Functional in vitro assays with endothelial cells, derived from uPAR-deficient and PTEN heterozygous crossbred mice, demonstrated the impact of uPAR-dependent PTEN regulation on cell motility and survival. In an in vivo murine angiogenesis model uPAR-deficient PTEN heterozygous animals increased the impaired angiogenic phenotype of uPAR knockout mice and were able to reverse the high invasive potential of PTEN heterozygots. Our data provide first evidence that endogenous as well as exogenous soluble uPAR down-regulated PTEN in endothelial cells to support angiogenesis. The uPAR-induced PTEN regulation might represent a novel target for drug interference, and may lead to the development of new therapeutic strategies in anti-angiogenic treatment.

Genomic recombination of the mitochondrial atp6 gene in Arabidopsis thaliana at the protein processing site creates two different presequences.

In the mitochondrial genome of the flowering plant Arabidopsis thaliana the atp6 open reading frame is located on the border of one of the repeats resulting in two copies with different presequence extensions. The two presequences of 135 and 97 amino acids respectively show no similarity to each other, while the mature protein sequences are identical. Both preproteins are most likely synthesized in Arabidopsis mitochondria from promoter elements upstream of each copy. The presence of two arrangements in the mitochondrial genome of fertile Arabidopsis plants suggests this recombination to be unrelated to a cytoplasmic male sterile phenotype. This recombination precisely at the mature protein terminus is reminiscent of the domain shuffling model in protein evolution.

Suicidal ideation and temperament: an investigation among college students.

BACKGROUND: Suicide is a major health problem accounting for up to 1.5 percent of all deaths worldwide and represents one of the most common causes of death in adolescents and young adults. A number of studies has been performed to establish risk factors for suicide in patients with psychiatric disorders including temperamental features. This study set out to assess the relationship between suicidal ideation and temperament in young adults. METHODS: A cross-sectional sample of healthy college students (n=1381) was examined using a self-rating questionnaire. Suicidal ideation, social background, educational status, substance abuse, and affective temperament according to TEMPS-M were assessed. Predictors of lifetime suicidal ideation were examined in multivariate logistic regression analyses. RESULTS: Suicidal ideation was reported by 12.5% of all subjects at some point in their life and was higher in nicotine dependents, youth with alcohol related problems and users of illicit substances as well as in youth with lower educational status. Lifetime suicidal ideation was associated with the anxious, depressive and cyclothymic temperament in both sexes and the irritable temperament in males. These results remained significant after adjustment for smoking status, frequency of alcohol consumption, drug experience and educational status in a multivariate logistic regression analysis. LIMITATIONS: The use of self-rating instruments always reduces objectivity and introduces the possibility of misreporting. CONCLUSIONS: Considering the fact that many subjects completing suicide have never been diagnosed with mental disorders it might be reasonable to include an investigation of temperament in screenings for risk of suicide. This might be especially useful for health care professionals without mental health care background.

The rps4-gene is encoded upstream of the nad2-gene in Arabidopsis mitochondria.

In Arabidopsis mitochondria the nad2-gene consists of five exons (a-e) which are separated by three cis-splicing introns and one trans-splicing intron. Sequence analysis of the region upstream of exons a and b reveals an open reading frame encoding ribosomal protein S4 (rps4). In the second nad2 coding region (exons c-e) a pseudo tRNA(Tyr) sequence and a fragment of the plastid psbA gene are located upstream of the trans-spliced exon c. Primer extension analysis identifies RNA 5'-termini within the pseudo-tRNA(Tyr) confirming this sequence to be non-functional. Northern blot analysis suggests the rps4-gene to be cotranscribed with at least the first part of the nad2-gene. The rps4 and nad2 coding sequences as well as the first cis-intron and the trans-intron sequences of the nad2 gene are altered by RNA editing. RNA editing in the open reading frames improves in most instances conservation of the specified amino acids.

An rps14 pseudogene is transcribed and edited in Arabidopsis mitochondria.

Sequence analysis of the region upstream of the apocytochrome b (cob) gene in the Arabidopsis mitochondrial genome identifies an open reading frame with homology to ribosomal protein L5, (rpl5), and a pseudogene with similarity to ribosomal protein S14 (rps14) genes. Both cob and rpl5 genes have intact reading frames, but the rps14 homology is disrupted by a stop codon and a deleted nucleotide. The rpl5 gene, the rps14 pseudogene, and the cob gene are separated by one nucleotide and a 1604-nucleotide-long spacer respectively. A plastid-like tRNA(Ser) is encoded downstream from the cob gene. The entire region is transcribed into a 5-kb transcript, containing the rps14 pseudogene and the cob gene. Cob and rpl5 mRNAs are edited in several positions with different frequencies. The rps14 pseudogene is transcribed and edited in one position in common with other plants. Since no intact rps14 gene is found in the mitochondrial genome of Arabidopsis, the functional gene is presumably encoded in the nucleus.

Group-specific differences in the secondary structure of the 28S ribosomal RNA of yeasts.

Ribosomal RNA (rRNA) sequences represent a good taxonomic character. Even small but significant parts of rRNA molecules can be used as a basis for taxonomic conclusions. A highly variable region within the 28S ribosomal nucleotide sequences from various yeasts was analysed. Despite numerous nucleotide exchanges in this region the secondary structure is generally conserved as in helices 17.1 and 17.2. However, among the organisms analysed the basidiomycetous yeasts show an insertion of 30 nucleotides which is missing in other yeasts. In this feature the Taphrinales and Schizosaccharomycetaceae resemble the 28S rRNA of Saccharomyces carlsbergensis rather than that of the basidiomycetous yeasts. Optimal sequence alignment and a good understanding of the secondary structure is an indispensible prerequisite for any evaluation of the taxonomic significance of differences in ribosomal RNA nucleotide sequences.

Seed and vascular expression of a high-affinity transporter for cationic amino acids in Arabidopsis.

In most plants amino acids represent the major transport form for organic nitrogen. A sensitive selection system in yeast mutants has allowed identification of a previously unidentified amino acid transporter in Arabidopsis. AAT1 encodes a hydrophobic membrane protein with 14 membrane-spanning regions and shares homologies with the ecotropic murine leukemia virus receptor, a bifunctional protein serving also as a cationic amino acid transporter in mammals. When expressed in yeast, AAT1 mediates high-affinity transport of basic amino acids, but to a lower extent also recognizes acidic and neutral amino acids. AAT1-mediated histidine transport is sensitive to protonophores and occurs against a concentration gradient, indicating that AAT1 may function as a proton symporter. AAT1 is specifically expressed in major veins of leaves and roots and in various floral tissues--i.e., and developing seeds.

Mosaic open reading frames in the Arabidopsis thaliana mitochondrial genome.

In the mitochondrial genome of Arabidopsis thaliana eight mosaic open reading frames arose by recombination of fragments duplicated from one or more mitochondrial genes. These duplications represent unedited sequences, suggesting their derivation from genomic DNA rather than RNA. Five of the chimeric reading frames contain the information for the N-terminus of the original polypeptide and 5' upstream regions. These observations suggest that the generation of novel open reading frames in plant mitochondria can occur rather easily by chance extensions of duplicated gene fragments. The presence of so many mosaic open reading frames in the normal Arabidopsis thaliana mitochondrial genome suggests that such recombined sequences interfere only occasionally and fortuitously with the peak mitochondrial performance presumably required during pollen maturation, and usually do not cause a cytoplasmic male sterile phenotype.

Ribosomal protein S14 transcripts are edited in Oenothera mitochondria.

The gene encoding ribosomal protein S14 (rps14) in Oenothera mitochondria is located upstream of the cytochrome b gene (cob). Sequence analysis of independently derived cDNA clones covering the entire rps14 coding region shows two nucleotides edited from the genomic DNA to the mRNA derived sequences by C to U modifications. A third editing event occurs four nucleotides upstream of the AUG initiation codon and improves a potential ribosome binding site. A CGG codon specifying arginine in a position conserved in evolution between chloroplasts and E. coli as a UGG tryptophan codon is not edited in any of the cDNAs analysed. An inverted repeat 3' of an unidentified open reading frame is located upstream of the rps14 gene. The inverted repeat sequence is highly conserved at analogous regions in other Oenothera mitochondrial loci.

Transcripts of the NADH-dehydrogenase subunit 3 gene are differentially edited in Oenothera mitochondria.

A number of cytosines are altered to be recognized as uridines in transcripts of the nad3 locus in mitochondria of the higher plant Oenothera. Such nucleotide modifications can be found at 16 different sites within the nad3 coding region. Most of these alterations in the mRNA sequence change codon identities to specify amino acids better conserved in evolution. Individual cDNA clones differ in their degree of editing at five nucleotide positions, three of which are silent, while two lead to codon alterations specifying different amino acids. None of the cDNA clones analysed is maximally edited at all possible sites, suggesting slow processing or lowered stringency of editing at these nucleotides. Differentially edited transcripts could be editing intermediates or could code for differing polypeptides. Two edited nucleotides in an open reading frame located upstream of nad3 change two amino acids in the deduced polypeptide. Part of the well-conserved ribosomal protein gene rps12 also encoded downstream of nad3 in other plants, is lost in Oenothera mitochondria by recombination events. The functional rps12 protein must be imported from the cytoplasm since the deleted sequences of this gene are not found in the Oenothera mitochondrial genome. The pseudogene sequence is not edited at any nucleotide position.

The mitochondrial genome of Arabidopsis is composed of both native and immigrant information.

Plants contain large mitochondrial genomes, which are several times as complex as those in animals, fungi or algae. However, genome size is not correlated with information content. The mitochondrial genome (mtDNA) of Arabidopsis specifies only 58 genes in 367 kb, whereas the 184 kb mtDNA in the liverwort Marchantia polymorpha codes for 66 genes, and the 58 kb genome in the green alga Prototheca wickerhamii encodes 63 genes. In Arabidopsis' mtDNA, genes for subunits of complex II, for several ribosomal proteins and for 16 tRNAs are missing, some of which have been transferred recently to the nuclear genome. Numerous integrated fragments originate from alien genomes, including 16 sequence stretches of plastid origin, 41 fragments of nuclear (retro)transposons and two fragments of fungal viruses. These immigrant sequences suggest that the large size of plant mitochondrial genomes is caused by secondary expansion as a result of integration and propagation, and is thus a derived trait established during the evolution of land plants.

The nad4L gene is encoded between exon c of nad5 and orf25 in the Arabidopsis mitochondrial genome.

In the Arabidopsis thaliana mitochondrial genome the gene coding for subunit 4L of NADH dehydrogenase (nad4L) is located between exon c of the nad5 open reading frame and orf25. The physical proximity of these genes further supports the trans-splicing model for assembly of the nad5 mRNA. Some transcripts comprise the nad4L open reading frame cotranscribed with nad5 exon c and orf25, while other mRNAs contain only nad4L and orf25. Both open reading frames for nad4L and orf25 are edited in several positions with different frequencies.

Physical mapping of the mitochondrial genome of Arabidopsis thaliana by cosmid and YAC clones.

As part of the worldwide efforts at molecular analysis of Arabidopsis thaliana as a model plant the complete structure of the mitochondrial genome has been determined. The mitochondrial DNA molecules were mapped by restriction fragment analysis of more than 300 cosmid clones and purified mitochondrial DNA. The entire genome of 372 kb is contained in three different configurations of circular molecules and is split into two additional subgenomic molecules of 234 kb and 138 kb, respectively. These arrangements result from recombinations of the two sets of repeats present in combinations of inverted and/or direct orientation. Alignment of YAC clones confirms the in vivo presence of continuous DNA molecules of more than 300 kb in A. thaliana mitochondria. The presence of this comparatively large mitochondrial genome in a plant with one of the smallest nuclear genomes shows that different size constraints act upon the different genomes in plant cells.