Spiritual well-being, dignity-related distress and demoralisation at the end of life-effects of dignity therapy: a randomised controlled trial.

OBJECTIVES: This single-centre prospective randomised controlled study aimed to investigate the effectiveness of dignity therapy on spiritual well-being, demoralisation and dignity-related distress compared with standard palliative care. METHODS: A total of 111 terminally ill hospice patients were randomly allocated to one of two groups: dignity therapy plus standard palliative care (intervention group) or standard palliative care alone (control group). The main outcomes were meaning, peace, faith, loss of meaning and purpose, distress and coping ability, existential distress, psychological distress and physical distress. Assessments were conducted at baseline, 7-10 and 15-20 days. RESULTS: Following randomisation, 11 dropped out before baseline assessment and 33 after post-treatment assessment. A total of 67 patients completed the study, 35 in the experimental group and 32 in the control group. Repeated measures general linear model showed significant differences between groups on peace and psychological distress over time, but not on existential distress, physical distress, meaning and purpose, distress and coping ability, meaning and faith. Specifically, patients in the dignity therapy intervention maintained similar levels of peace from baseline to follow-up, whereas patients in the control group significantly declined in peace during the same time period. Moreover, psychological distress significantly decreased from pretreatment to post-treatment in the intervention group and increased in the control group. CONCLUSIONS: Dignity therapy may be an effective intervention in maintaining sense of peace for terminally ill patients. The findings of our study are of relevance in palliative care and suggest the potential clinical utility of this psychological intervention.

Dignity Therapy Helps Terminally Ill Patients Maintain a Sense of Peace: Early Results of a Randomized Controlled Trial.

Introduction: Dignity Therapy (DT) is a brief, individualized, narrative psychotherapy developed to reduce psychosocial and existential distress, and promote dignity, meaning, and hope in end of life patients. Previous studies have shown that DT was effective in reducing anxiety and depression, and improving dignity-related distress. However, less is known about its efficacy on spiritual well-being. The aim of this study is to contribute to the existing literature by investigating the effects of DT on specific dimensions of spiritual well-being, demoralization and dignity-related distress in a sample of terminally ill patients. Methods: A randomized, controlled trial was conducted with 64 terminally ill patients who were randomly assigned to the intervention group (DT + standard palliative care) or the control group (standard palliative care alone). The primary outcome measures were Meaning, Peace, and Faith whereas the secondary outcome measures were (loss of) Meaning and purpose, Distress and coping ability, Existential distress, Psychological distress, and Physical distress. All measures were assessed at baseline (before the intervention), 7-10 and 15-20 days after the baseline assessment. The trial was registered with ClinicalTrials.gov (Protocol Record NCT04256239). Results: The MANOVA yielded a significant effect for the Group X Time interaction. ANOVA with repeated measures showed a significant effect of time on peace and a significant Group X Time interaction effect on peace. Post hoc comparisons revealed that, while there was a decrease in peace from pre-treatment to follow-up and from post-treatment to follow-up in the control group, there was no such trend in the intervention group. Discussion: This study provides initial evidence that patients in the DT intervention maintained similar levels of peace from pre-test to follow-up, whereas patients in the control group showed a decrease in peace during the same time period. We did not find significant longitudinal changes in measures of meaning, faith, loss of meaning and purpose, distress and coping ability, existential, psychological and physical distress. The findings of our study are of relevance in palliative care and suggest the potential clinical utility of DT, since they offer evidence for the importance of this intervention in maintaining peace of mind for terminally ill patients.

RrS1-like sequences of water frogs from Central Europe and around the Aegean Sea: chromosomal organization, evolution, possible function.

RrS1-like sequences of water frogs (genus Pelophylax) display varied genomic organization, whereas the centromeric hybridization pattern reveals species-specific differences. Using fluorescent in situ hybridization, Pelophylax cf. bedriagae, Pelophylax kurtmuelleri, and Pelophylax ridibundus showed a hybridization signal at centromeres of chromosomes 1-5, but in P. kurtmuelleri the medium-small chromosome labeled was 10 rather than 8. Pelophylax cretensis had almost 16 of 26 centromeres labeled, as did Pelophylax lessonae from Poland when its chromosomes are hybridized with a homologous probe. When StuI-digested genomic DNA was hybridized with RrS1 probe, hybridization ladders for P. ridibundus from Poland have evenly spaced steps (about 100 bp) of uniform intensity from about 200 bp upward. Steps in hybridization ladders from circum-Aegean taxa vary in intensity: larger, odd-numbered steps are often fainter. A strong double band (800/900 bp) in Anatolian P. cf. bedriagae, emphasized by a weak 700 bp band, distinguishes them from P. kurtmuelleri from the Peloponnisos, in which the 900 bp band is almost absent. The ladder in P. cretensis lacks odd-numbered steps. A and B repeats, observed originally within the RrS1 satellite of P. ridibundus, occur also in the circum-Aegean frogs and in P. lessonae, Pelophylax epeiroticus, Pelophylax saharicus, and Pelophylax shqipericus. It is plausible that AB dimers or ABB trimers rather than A or B monomers correspond to functional/evolutionary units. The presence of regions similar to yeast CDEs and mammalian CENP-B boxes suggests a role for RrS1 sequences in centromere organization.

Daz- and pumilio-like genes are asymmetrically localized in Pelophylax (Rana) oocytes and are expressed during early spermatogenesis.

In many organisms, the specification of cell fate and the formation of embryonic axes depend on a proper distribution of maternal mRNAs during oogenesis. Asymmetrically localized determinants are required both for embryonic axes and germline determination in anuran amphibians. As a model system of these processes, we have used a species complex of the genus Pelophylax (Rana), characterized by a hybridogenetic reproduction that involves events of genome exclusion and endoreduplication during meiosis in both sexes. With the aim of characterizing the still largely unknown molecular events regulating Pelophylax gametogenesis, we have isolated in this animal model homologues of the deleted in AZoospermia-like (DAZl) and pumilio gene families (named RlDazl and RlPum1, respectively), which encode posttranscriptional regulators. Expression pattern analysis of these genes showed that RlDazl is exclusively expressed in gonadal tissues, whereas RlPum1 is expressed in both somatic tissues and gonads. In situ hybridization carried out on gonads revealed that the two transcripts were asymmetrically localized along the animal-vegetal (A-V) axis of oocytes. In particular, the RlDazl transcript progressively collected to the vegetal pole during oogenesis, whereas the RlPum1 mRNA was preferentially enriched at the animal hemisphere. In adult testes, RlDazl and RlPum1 were expressed in specific phases of spermatogenetic divisions as shown by immunostaining with anti-H3 phosphohistone antibody. Our results indicate that RlDazl and RlPum1 represent two early indicators of oocyte polarity in this hybridogenetic vertebrate model. Additionally, RlDazl share with vertebrate DAZ- like genes a germ cell-specific expression pattern.

Endoplasmic reticulum stress and alteration in calcium homeostasis are involved in cadmium-induced apoptosis.

Cadmium, a toxic environmental contaminant, exerts adverse effects on different cellular pathways such as cell proliferation, DNA damage and apoptosis. In particular, the modulation of Ca(2+) homeostasis seems to have an important role during Cd(2+) injury, but the precise assessment of Ca(2+) signalling still remains poorly understood. We used aequorin-based probes specifically directed to intracellular organelles to study Ca(2+) changes during cadmium injury. We observed that cadmium decreased agonist-evoked endoplasmic reticulum (ER) Ca(2+) signals and caused a 40% inhibition of sarcoplasmic-ER calcium ATPases activity. Moreover, time course experiments correlate morphological alterations, processing of xbp-1 mRNA and caspase-12 activation during cadmium administration. Finally, the time response of ER to cadmium injury was compared with that of mitochondria. In conclusion, we highlighted a novel pathway of cadmium-induced cell death triggered by ER stress and involving caspase-12. Mitochondria and ER pathways seemed to share common time courses and a parallel activation of caspase-12 and caspase-9 seemed likely to be involved in acute cadmium toxicity.

Gametogenesis of intergroup hybrids of hemiclonal frogs.

European water frog hybrids Rana esculenta (R. ridibundaxR. lessonae) reproduce hemiclonally, by hybridogenesis: in the germ line they exclude the genome of one parental species and produce haploid gametes with an unrecombined genome of the other parental species. In the widespread L-E population system, both sexes of hybrids (E) coexist with R. lessonae (L). They exclude the lessonae genome and produce ridibunda gametes. In the R-E system, hybrid males coexist with R. ridibunda (R); they exclude either their ridibunda or their lessonae genome and produce sperm with a lessonae or with a ridibunda genome or a mixture of both kinds of sperm. We examined 13 male offspring, 12 of which were from crosses between L-E system and R-E system frogs. All were somatically hybrid. With one exception, they excluded the lessonae genome in the germ line and subsequently endoreduplicated the ridibunda genome. Spermatogonial metaphases contained a haploid or a diploid number of ridibunda chromosomes, identified through in situ hybridization to a satellite DNA marker, and by spermatocyte I metaphases containing a haploid number of ridibunda bivalents. The exception, an F1 hybrid between L-E system R. lessonae and R-E system R. ridibunda, was not hybridogenetic, showed no genome exclusion, and evidenced a disturbed gametogenesis resulting from the combination of two heterospecific genomes. None of the hybridogenetic hybrids showed any cell lines excluding the ridibunda genome, the pattern most frequent in hybrids of the R-E system, unique to that system, and essential for its persistence. A particular combination of R-E system lessonae and R-E system ridibunda genomes seems necessary to induce the R-E system type of hemiclonal gametogenesis.

Differential expression of two vasa/PL10-related genes during gametogenesis in the special model system Rana.

Germline cell fate decisions are primarily controlled at the post-transcriptional level with DEAD-box RNA helicases playing a crucial role in germline development. In this study, we report the identification of two DEAD-box vasa/PL10 orthologues (RlVlg and RlPL10) in a species complex of the genus Rana, characterized by hybridogenetic reproduction, an enigmatic process that involves the exclusion of an individual genome, and endoreduplication events. Both genes were expressed during the early stages of gametogenesis of R. ridibunda, R. lessonae, and their natural hybrid R. esculenta. RlVlg expression was germline specific. On the other hand, RlPL10 was also expressed in somatic tissues, although only at low levels. The two genes were expressed in different phases of mitotic and meiotic spermatogenetic divisions as demonstrated by immunostaining with an anti-H3 phosphohistone antibody. The data indicate that RlVlg and RlPL10 may represent useful markers for dissecting the molecular aspects of genome exclusion and endoreduplication of the hybridogenetic gametogenesis.