Efficacy of a self-management education programme on patients with type 2 diabetes in primary care: A randomised controlled trial.

AIM: The purpose of this study was to assess the efficacy of the Spanish Diabetes Self-Management Program (SDSMP) versus usual care in adults with type 2 diabetes mellitus (T2DM) residing in a Spanish region. METHODS: A two-year follow-up randomised controlled trial. The intervention consisted of 6 weekly structured peer-to-peer workshops. The primary outcome was change in HbA1c levels. Secondary outcomes included other clinical measures, quality of life, self-efficacy, life-style changes, medication and use of healthcare services. Mixed effect models were fitted. RESULTS: n=297 patients were recruited in each study arm. Baseline HbA1c levels were comparable in both groups with an overall mean 7.1 (SD=1.2). The intervention did not significantly modify HbA1c, or other cardiovascular variables. Significant improvements were seen in self-efficacy, and in particularly its disease control component. Certain differences were also observed in the use of healthcare resources and medication consumption. High workshop participation and satisfaction rates were achieved. CONCLUSION: HbA1c reductions are difficult to obtain in adequately controlled patients. On the other hand, raising awareness on one's disease can increase disease control self-efficacy. This finding, accompanied by reduced medication consumption and healthcare use rates, highlights that usual care would be benefited by incorporating certain SDSMP aspects. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01642394.

Impact of a self-care education programme on patients with type 2 diabetes in primary care in the Basque Country.

BACKGROUND: Type 2 diabetes mellitus (DM2) is a disease with high prevalence and significant impact in terms of mortality and morbidity. The increased prevalence of the disease requires the implementation of new strategies to promote patient self-management. The Spanish Diabetes Self-Management Program (SDSMP) has proven to be effective in other settings. The objective of this study is to assess its effectiveness in terms of care for DM2 patients in primary care settings within the Basque Health Service - Osakidetza (Spain). METHOD/DESIGN: This is a randomised clinical trial in which patients diagnosed with DM2, 18-79 years of age, from four health regions within the Basque Health Service will be randomised into two groups: an intervention group, who will follow the SDSMP, and a control group, who will receive usual care in accordance with the clinical guidelines for DM2 and existing regulations in our region. The intervention consists of 2,5 hour-group sessions once a week for six weeks. The sessions cover target setting and problem solving techniques, promotion of physical exercise, basic knowledge of nutrition, proper use of medication, effective communication with relatives and health professionals, and basic knowledge about DM2 and its complications. This content is complemented by educational material: books, leaflets and CDs. The primary outcome measure will be the change in glycated haemoglobin (HbA1c), and secondary outcome measures will include changes in levels of physical activity and intake of fruit and vegetables, cardiovascular risk, quality of life, self-efficacy, number of consultations and drug prescriptions. The results will be analysed 6, 12 and 24 months after the intervention. DISCUSSION: If the intervention were to be effective, the programme should be spread to the entire diabetic population in the Basque Country and it could also be applied for other diseases. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01642394.

The giant fibrillar center: a nucleolar structure enriched in upstream binding factor (UBF) that appears in transcriptionally more active sensory ganglia neurons.

This paper studies the molecular organization, neuronal distribution and cellular differentiation dynamics of the giant fibrillar centers (GFCs) of nucleoli in rat sensory ganglia neurons. The GFC appeared as a round nucleolar domain (1-2 microm in diameter) partially surrounded by the dense fibrillar component and accompanied by numerous small FCs. By immunocytochemistry, the GFC concentrated the upstream binding factor, which may serve as a marker of this structure, and also contain RNA polymerase I, DNA topoisomerase I, SUMO-1 and Ubc9. However, they lack ubiquitin-proteasome conjugates and 20S proteasome. Transcription assay with 5'-fluorouridine incorporation revealed the presence of nascent RNA on the dense fibrillar component of the neuronal nucleolus, but not within the low electron-density area of the GFC. The formation of GFCs is neuronal size dependent: they were found in 58%, 30% and 0% of the large, medium and small neurons, respectively. GFCs first appeared during the postnatal period, concomitantly with a stage of neuronal growth, myelination and bioelectrical maturation. GFCs were not observed in segregated nucleoli induced by severe inhibition of RNA synthesis. We suggest that the formation of GFCs is associated with a high rate of ribosome biogenesis of the transcriptionally more active large-size neurons.

cAMP-dependent reorganization of the Cajal bodies and splicing machinery in cultured Schwann cells.

It is well established that forskolin-induced elevation of cAMP results in activation of DNA synthesis in Schwann cell cultures. This promitotic response is partially mediated by the Cdk2, which is required for the transition from the G1 to the S phase of the cell cycle. In the present study, we analyze the effects of cAMP elevation in cultured Schwann cells on the transcriptional activity and on the organization of two nuclear compartments involved in pre-mRNA processing: Cajal bodies (CBs) and splicing factor compartments. Our immunofluorescence and quantitative studies show that forskolin treatment induces a 5.6-fold increase in the proportion of S phase Schwann cells, detected by a short pulse (20 min) of BrdU incorporation. This increase in DNA synthesis correlates with an activation of global transcription, as is indicated by the higher nuclear incorporation of BrU in nascent RNA. Forskolin treatment significantly increases the percentage of Schwann cells containing typical CBs, which concentrate spliceosomal snRNPs and the survival motor neuron (SMN) protein. This increase in the number of CBs closely correlates with the activation of transcription. Moreover, the occurrence of CBs is significantly higher in BrdU (+) cells than in BrdU (-) cells, indicating that entry in the S phase promotes the formation of CBs. During the S phase, Schwann cell nuclei display higher Cdk2 nuclear staining and concentrate this kinase in CBs. Forskolin also induces a redistribution of the pre-mRNA splicing factors in Schwann cells. Primary cultures of Schwann cells provide an excellent physiological model to demonstrate that the assembly of CBs is a transcription- and replication-dependent cellular event. Moreover, the S phase accumulation of Cdk2 observed in Schwann cells supports a functional link between CBs and DNA replication, which is mediated by the possible participation of CBs in the regulatory control of histone gene expression.

Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes, ubiquitin, and protein substrates of proteasome.

Nuclear bodies represent a heterogeneous class of nuclear structures. Herein, we describe that a subset of nuclear bodies is highly enriched in components of the ubiquitin-proteasome pathway of proteolysis. We coined the term clastosome (from the Greek klastos, broken and soma, body) to refer to this type of nuclear body. Clastosomes contain a high concentration of 1) ubiquitin conjugates, 2) the proteolytically active 20S core and the 19S regulatory complexes of the 26S proteasome, and 3) protein substrates of the proteasome. Although detected in a variety of cell types, clastosomes are scarce under normal conditions; however, they become more abundant when proteasomal activity is stimulated. In contrast, clastosomes disappear when cells are treated with proteasome inhibitors. Protein substrates of the proteasome that are found concentrated in clastosomes include the short-lived transcription factors c-Fos and c-Jun, adenovirus E1A proteins, and the PML protein. We propose that clastosomes are sites where proteolysis of a variety of protein substrates is taking place.

Structural and functional compartmentalization of the cell nucleus in supraoptic neurons.

It is well-established that the neuronal cell nucleus is organized in discrete compartments involved in transcription and RNA processing. The main nuclear compartments in neurons include the chromosome territories, the nucleolus, nuclear speckles of splicing factors, Cajal bodies, and nuclear rodlets. The supraoptic nucleus (SON) neurons provide a powerful model in vivo to study the organization of these nuclear compartments in response to variations of cellular activity. The upregulation of transcription in SON neurons under chronic hyperosmolar conditions is associated with 1) nuclear and nucleolar enlargement, 2) dispersion of chromatin, 3) reduction in the size of nuclear speckles, 4) increase in the number of Cajal bodies implicated in the maturation of splicing small nuclear ribonucleoproteins, and 5) proliferation of the fibrillar centers of the nucleolus, the sites of nucleolar transcription of ribosomal genes. These changes revert after the cessation of the activation by rehydration of animals. Under conditions of neuronal stress induced by hypertonic saline injection, SON neurons exhibit an early response of downregulation of transcription. This is accompanied by chromatin condensation, redistribution of splicing factors, reduction in the number of Cajal bodies, and microsegregation of the fibrillar and granular components of the nucleolus and disruption of its fibrillar centers, all of which are associated with a transitory expression of c-Fos. These changes progressively revert and at 24 hours after the stress induction a rebound upregulation of transcription is observed. These findings illustrate the transcription-dependent organization and behavior of nuclear compartments in the neuronal model of magnocellular neurosecretory cells of the hypothalamus.