Accumulation of 125I-labelled thiouracil and propylthiouracil in murine melanotic melanomas.

We have shown that thioamides are incorporated as false precursors into melanin during its synthesis. To be clinically useful in the diagnosis or therapy of melanotic melanomas, they would have to be tagged with an appropriate isotope or possibly a cytotoxic moiety. 125I-Thiouracil (125I-TU) is here shown to be accumulated in the melanin of melanotic melanomas transplanted into mice in a similar way as is 14C-thiouracil (14C-TU). 125I-TU gives tumour/liver and tumour/muscle ratios up to 22 and 778 respectively, at 4 days after administration. 125I-TU is accumulated by melanoma cells in vitro more effectively than 14C-TU (125I-TU/14C-TU, 2.7), while the in vivo accumulation into melanomas is slightly lower for 125I-TU as compared to 14C-TU (125I-TU/14C-TU, 0.35). This appears to be due to a partial deiodination (less than 14% of the dose within 4 days) and probably a more rapid excretion of 125I-TU or its metabolite(s). The accumulation of radioactivity in the thyroid can essentially be eliminated by pretreatment with potassium iodide and/or thyroxine. 125I-Propylthiouracil is also accumulated in melanotic melanoma cells in vivo and in vitro, but at a lower level than in 125I-TU and 14C-TU

Sensory Ataxic Neuropathy in Golden Retriever Dogs Is Caused by a Deletion in the Mitochondrial tRNATyr Gene

Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNATyr gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0–11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNATyr had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNATyr gene is the causative mutation for SAN

Understanding Interorganizational Learning Based on Social Spaces and Learning Episodes

Different organizational settings have been gaining ground in the world economy, resulting in a proliferation of different forms of strategic alliances that translate into a growth in the number of organizations that have started to deal with interorganizational relationships with different actors. These circumstances reinforce Crossan, Lane, White and Djurfeldt (1995) and Crossan, Mauer and White (2011) in exploring what authors refer to as the fourth, interorganizational, level of learning. These authors, amongst others, suggest that the process of interorganizational learning (IOL) warrants investigation, as its scope of analysis needs widening and deepening. Therefore, this theoretical essay is an attempt to understand IOL as a dynamic process found in interorganizational cooperative relationships that can take place in different structured and unstructured social spaces and that can generate learning episodes. According to this view, IOL is understood as part of an organizational learning continuum and is analyzed within the framework of practical rationality in an approach that is less cognitive and more social-behavioral

Psychodynamic Guided Self-help for Adult Deperssion through the Internet: A Randomised Controlled Trial.

Abstract Background and aims: Psychodynamic psychotherapy (PDT) is an effective treatment for major depressive disorder (MDD), but not all clients with MDD can receive psychotherapy. Using the Internet to provide psychodynamic treatments is one way of improving access to psychological treatments for MDD. The aim of this randomised controlled trial was to investigate the efficacy of an Internet-based psychodynamic guided self-help treatment for MDD. Methods: Ninety-two participants who were diagnosed with MDD according to the Mini-International Neuropsychiatric Interview were randomised to treatment or an active control. The treatment consisted of nine treatment modules based on psychodynamic principles with online therapist contact. The active control condition was a structured support intervention and contained psychoeducation and scheduled weekly contacts online. Both interventions lasted for 10 weeks. The primary outcome measure was the Beck Depression Inventory-II (BDI-II). Results: Mixed-effects model analyses of all randomised participants showed that participants receiving Internet-based PDT made large and superior improvements compared with the active control group on the BDI-II (between-group Cohen’s d = 1.11). Treatment effects were maintained at a 10-month follow-up. Conclusions: Internet-based psychodynamic guided self-help is an efficacious treatment for MDD that has the potential to increase accessibility and availability of PDT for MDD

“It’s ok that I feel like this”: a qualitative study of adolescents’ and parents’ experiences of facilitators, mechanisms of change and outcomes in a joint emotion regulation group skills training

Abstract Background Emotion regulation difficulties underlie several psychiatric conditions, and treatments that focus on improving emotion regulation can have an effect on a broad range of symptoms. However, participants’ in-depth experiences of participating in emotion regulation treatments have not been much studied. In this qualitative study, we investigated participants’ experiences of a joint emotion regulation group skills training in a child and adolescent psychiatric outpatient setting. Methods Twenty-one participants (10 adolescents and 11 parents) were interviewed about their experiences after they had participated in a seven-session transdiagnostic emotion regulation skills training for adolescents and parents. The aim of the skills training was to decrease emotion regulation difficulties, increase emotional awareness, reduce psychiatric symptoms, and enhance quality of life. The skills training consisted of psychoeducation about emotions and skills for regulating emotions. The interviews were transcribed and analysed using reflexive thematic analysis. Results The analysis resulted in three overarching themes: Parent – Child processes, Individual processes, and Group processes. The result showed that participants considered an improved parent-child relationship to be the main outcome. Increased knowledge, emotion regulation skills and behavioural change were conceptualised as both mechanisms of change and outcomes. The group format, and the fact that parents and adolescents participated together, were seen as facilitators. Furthermore, the participants experienced targeting emotions in skills training as meaningful and helpful. Conclusion The results highlight the potential benefits of providing emotion regulation skills training for adolescents and parents together in a group format to improve the parent-child relationship and enable the opportunity to learn skills