A Brief Cognitive Analytic Therapy-Informed Approach for Young People That Have Self-Injured (CATCH-Y): A Case Series.

BACKGROUND: Non-suicidal self-injury (NSSI) presents an increasingly prevalent problem for young people; however, there remains a scarce evidence base for effective, scalable treatments for adolescents. This study aimed to assess the feasibility and acceptability of a brief, cognitive analytic therapy (CAT)-informed intervention for young people who engage in NSSI (CATCH-Y). METHODS: A case series design recruited 13 young people who met the inclusion and exclusion criteria to participate in the five-session intervention. Eligible participants were aged 13-17 years (M = 15.15, SD = 1.28) and had engaged in NSSI at least once in the previous 6 months. Feasibility and acceptability were measured via recruitment, retention, qualitative feedback and missing data. The secondary outcome measures of personal recovery and motivation were administered pre- and post-assessment, with measures of depressive symptoms and urges to self-injure. RESULTS: The intervention was found to be largely feasible and acceptable with high rates of recruitment, retention and pre-/post-assessment data completeness. Measures showed preliminary support for positive change in rates of NSSI, urges to self-harm, low mood and personal recovery, although results were mixed. Completion rates for remote assessments were low. CONCLUSIONS: The findings of this study support further evaluation of the CATCH-Y intervention on a larger scale. In-person assessments may be preferable to remote to ensure good completion rates.

The Biomolecular Interaction Network Database and related tools 2005 update.

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues.

Isolation of a Candida glabrata homologue of RAP1, a regulator of transcription and telomere function in Saccharomyces cerevisiae.

To study the function of RAP1, an essential gene involved in the regulation of transcriptional activation, silencing and the telomere function in Saccharomyces cerevisiae, we isolated a Candida glabrata gene that complements the growth defect of a S. cerevisiae rap1 conditional mutant. The DNA sequence of the cloned gene, which we designated CgRAP1, predicted a 2064 bp open reading frame encoding a 687 amino acid protein with an overall identity of 65% and a similarity of 78% to Rap1p from S. cerevisiae.

Isolation of GCR1, a major transcription factor of glycolytic genes in Saccharomyces cerevisiae, from Kluyveromyces lactis.

To study the function of GCR1, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, a Kluyveromyces lactis gene that complements the growth defect of a S. cerevisiae Deltagcr1 mutant was isolated. Introduction of this gene into the Deltagcr1 mutant also restored the activities of glycolytic enzymes. DNA sequencing of KlGCR1 predicted an open reading frame of a 767 amino acid protein with an overall identity of 33% and similarity of 48% to Gcr1p from S. cerevisiae. Its DDBJ/EMBL/GenBank Accession No. is AB046391.

In vivo analysis of functional regions within yeast Rap1p.

We have analyzed the in vivo importance of different regions of Rap1p, a yeast transcriptional regulator and telomere binding protein. A yeast strain (SCR101) containing a regulatable RAP1 gene was used to test functional complementation by a range of Rap1p derivatives. These experiments demonstrated that the C terminus of the protein, containing the putative transcriptional activation domain and the regions involved in silencing and telomere function, is not absolutely essential for cell growth, a result confirmed by sporulation of a diploid strain containing a C terminal deletion derivative of RAP1. Northern analysis with cells that expressed Rap1p lacking the transcriptional activation domain revealed that this region is important for the expression of only a subset of Rap1p-activated genes. The one essential region within Rap1p is the DNA binding domain. We have investigated the possibility that this region has additional functions. It contains two Myb-like subdomains separated by a linker region. Individual point mutations in the linker region had no effect on Rap1p function, although deletion of the region abolished cell growth. The second Myb-like subdomain contains a large unstructured loop of unknown function. Domain swap experiments with combinations of elements from DNA binding domains of Rap1p homologues from different yeasts revealed that major changes can be made to the amino acid composition of this region without affecting Rap1p function.

Evidence for the inactivation of multiple replicative lifespan genes in immortal human squamous cell carcinoma keratinocytes.

Human keratinocyte immortality is genetically recessive to the normal phenotype of limited replicative lifespan and appears to require the dysfunction of p53 and the cyclin D-Cdk inhibitor p16. In order to test for the inactivation of other candidate replicative lifespan genes in the immortal cells of human tumors, we developed a series of mortal and immortal keratinocyte cultures derived from neoplastic lesions of the head and neck which were amenable to molecular genetic analysis by the loss of heterozygosity (LOH) technique. The results indicate that keratinocyte immortalization in head and neck squamous cell carcinoma (SCC-HN) development involves the inactivation of at least two further pathways to senescence and four in all. Chromosomes 1, 4 and 7 carry genes representing immortality complementation groups C, B and D respectively and immortal keratinocytes showed LOH at either 4q32-q34 between D4S1554 and D4S171 (group B) or 7q31 (group D) but never 1q25 (group C). These results tentatively suggest that the genes responsible for the immortality complementation groups encode proteins on the same pathway to senescence. In addition, all of the immortal keratinocyte lines possessed high levels of telomerase activity and a suppressor of telomerase activity has been mapped to the short arm of chromosome 3p. Five out of eight lines showed LOH at 3p21.2-p21.3, a region which may carry a gene capable of suppressing SCC-HN telomerase. However, alternative mechanisms of telomerase reactivation were also suggested by our results. None of the above genetic alterations were seen in seven senescent neoplastic keratinocyte cultures. Other loci harbouring antiproliferative genes implicated in replicative lifespan showed few or no alterations and any alterations seen were additional to those described above.

Significance of a partial or slow response to front-line chemotherapy in the management of intermediate-grade or high-grade non-Hodgkin's lymphoma: a literature review.

PURPOSE: The purpose of this review was to assess the outcome of patients with non-Hodgkin's lymphoma (NHL) who achieve an incomplete or slow response to front-line chemotherapy and to determine whether salvage treatment with intensive combination chemotherapy with or without autologous bone marrow transplantation (ABMT) is successful in such patients. METHODS: A comprehensive literature search of studies using combination chemotherapy for the front-line therapy of advanced-stage intermediate- and high-grade NHL and for salvage therapy of patients with a partial response (PR) was reviewed. RESULTS: The median survival duration of patients with a PR ranged between 5 to 14 months, while the median survival duration of patients with a complete response (CR) was not reached in many studies. For patients in CR, the probability of survival at 24 months ranged between 0.79 to 1, while for patients in PR it ranged from 0 to 0.31. The rapidity of a response to front-line therapy was often found to be of prognostic importance. Patients who relapsed after a PR to front-line therapy had similar outcomes to intensive salvage therapy as those who relapsed after a CR. ABMT performed immediately after a PR to induction therapy, before progressive disease occurred, resulted in high CR rates in nonrandomized studies. CONCLUSION: Patients with aggressive NHL who experience a PR or who respond slowly to front-line chemotherapy have a poor prognosis. Early introduction of dose-intensive salvage therapy before the development of progressive disease may benefit patients with a PR and requires testing in randomized clinical trials.