A randomised control trial of an Internet-based cognitive behaviour treatment for mood disorder in adults with chronic spinal cord injury.

STUDY DESIGN: Prospective parallel waitlist randomised controlled trial. OBJECTIVES: Evaluate the feasibility and effectiveness of an Internet-based psychological intervention treating comorbid mood disorder in adults with spinal cord injury (SCI). Improved mood and satisfaction with life were primary outcomes. SETTING: Victoria, Australia. INTERVENTION: Electronic Personal Administration of Cognitive Therapy (ePACT). MEASURES: Depression, Anxiety and Stress Scale-Short Form (DASS21), Personal Well-being Index, Helplessness subscale of the Spinal Cord Lesion Emotional Well-being Scale v1 Australia, at each time point.Participant qualifying criteria:Adults (18-70 years), chronic SCI, attend SCI review clinic at Austin or Caulfield Hospital and score above normative threshold of the Depression, Anxiety and Stress Scale-Short Form (DASS21). METHODS: Forty-eight participants completed Time 2 post intervention (n=23) or time equivalent for waitlist control group (n=25) telephone interviews. The measures were repeated a third time (Time 3) for a small subgroup (n=12) at 6 months post intervention within the study implementation time frame. RESULTS: Univariate within group analyses revealed significant improvement in mood in the intervention group at Time 2: (lower depression (effect size (ES)=0.4), anxiety (ES=0.4) and stress (ES=0.3)) and higher satisfaction with life (ES=0.2). Waitlist control group improved in depression only (ES=0.3) by Time 2. Multilevel variance components analyses, although not as positive, were still encouraging. Improvement in mood symptoms was maintained in the small group reinterviewed at Time 3. CONCLUSION: Although Internet-based interventions for mental health issues in SCI not a solution for all, our results indicate that they are a potentially valuable addition to the currently available options.

Prevalence of mood disturbance in Australian adults with chronic spinal cord injury.

BACKGROUND: There is little understanding of the prevalence of mental health issues in people with spinal cord injury (SCI) after they leave rehabilitation or how mental health issues can alter over time. AIM: The aims were to (i) determine the prevalence of mood disturbance in adults with chronic SCI living in the community, (ii) ascertain whether the prevalence of mood disturbance had changed since a previous study in 2004-2005 and (iii) establish whether people with chronic SCI remain vulnerable to mood disturbance, irrespective of time since injury. METHODS: Prospective, open-cohort case series. Participants were 573 community-based adults with a chronic SCI. The depression, anxiety and stress scale - short version was used. Analyses included simple descriptors, Chi-squared and repeated measures t-tests. RESULTS: Nearly half of participants (n = 263/573; 46%) reported symptoms indicating mood disturbance, which was similar to the level found in the previous study. While the presence of mood disturbance persisted in 23% of adults (n = 26) and 46 (41%) were in the 'below threshold' category, just over a third of the adults who participated in both studies (n = 111) experienced a change (n = 21, 19% mood disturbance resolved and n = 18, 16% mood disturbance developed). CONCLUSION: Both resilience and change are common. At no time after SCI is the risk of mental health problems considered reduced or even stable. These results highlight the importance of regular mental health reviews even in those who have previously displayed good resilience.

Multimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27).

AIMS/HYPOTHESIS: Non-invasive diagnostic tools specific for pancreatic beta cells will have a profound impact on our understanding of the pathophysiology of metabolic diseases such as diabetes. The objective of this study was to use molecular imaging probes specifically targeting beta cells on human samples and animal models using state-of-the-art imaging modalities (fluorescence and PET) with preclinical and clinical perspective. METHODS: We generated a monoclonal antibody, 8/9-mAb, targeting transmembrane protein 27 (TMEM27; a surface N-glycoprotein that is highly expressed on beta cells), compared its expression in human and mouse pancreas, and demonstrated beta cell-specific binding in both. In vivo imaging was performed in mice with subcutaneous insulinomas overexpressing the human TMEM27 gene, or transgenic mice with beta cell-specific hTMEM27 expression under the control of rat insulin promoter (RIP-hTMEM27-tg), using fluorescence and radioactively labelled antibody, followed by tissue ex vivo analysis and fluorescence microscopy. RESULTS: Fluorescently labelled 8/9-mAb showed beta cell-specific staining on human and mouse pancreatic sections. Real-time PCR on islet cDNA indicated about tenfold higher expression of hTMEM27 in RIP-hTMEM27-tg mice than in humans. In vivo fluorescence and PET imaging in nude mice with insulinoma xenografts expressing hTMEM27 showed high 8/9-mAb uptake in tumours after 72 h. Antibody homing was also observed in beta cells of RIP-hTMEM27-tg mice by in vivo fluorescence imaging. Ex vivo analysis of intact pancreas and fluorescence microscopy in beta cells confirmed these findings. CONCLUSIONS/INTERPRETATION: hTMEM27 constitutes an attractive target for in vivo visualisation of pancreatic beta cells. Studies in mouse insulinoma models and mice expressing hTMEM27 demonstrate the feasibility of beta cell-targeted in vivo imaging, which is attractive for preclinical investigations and holds potential in clinical diagnostics.

Taspoglutide, a novel human once-weekly GLP-1 analogue, protects pancreatic ß-cells in vitro and preserves islet structure and function in the Zucker diabetic fatty rat in vivo.

AIM: Glucagon-like peptide-1 (GLP-1) has protective effects on pancreatic ß-cells. We evaluated the effects of a novel, long-acting human GLP-1 analogue, taspoglutide, on ß-cells in vitro and in vivo. METHODS: Proliferation of murine pancreatic ß (MIN6B1) cells and rat islets in culture was assessed by imaging of 5-ethynyl-2'-deoxyuridine-positive cells after culture with taspoglutide. Apoptosis was evaluated with the transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labelling assay in rat insulinoma (INS-1E) cells and isolated human islets exposed to cytokines (recombinant interleukin-1ß, interferon-γ, tumour necrosis factor-α) or lipotoxicity (palmitate) in the presence or absence of taspoglutide. Islet morphology and survival and glucose-stimulated insulin secretion in perfused pancreata were assessed 3-4 weeks after a single application of taspoglutide to prediabetic 6-week-old male Zucker diabetic fatty (ZDF) rats. RESULTS: Proliferation was increased in a concentration-dependent manner up to fourfold by taspoglutide in MIN6B1 cells and was significantly stimulated in isolated rat islets. Taspoglutide almost completely prevented cytokine- or lipotoxicity-induced apoptosis in INS-1E cells (control 0.5%, cytokines alone 2.2%, taspoglutide + cytokines 0.6%, p < 0.001; palmitate alone 8.1%, taspoglutide + palmitate 0.5%, p < 0.001) and reduced apoptosis in isolated human islets. Treatment of ZDF rats with taspoglutide significantly prevented ß-cell apoptosis and preserved healthy islet architecture and insulin staining intensity as shown in pancreatic islet cross sections. Basal and glucose-stimulated insulin secretion of in situ perfused ZDF rat pancreata was normalized after taspoglutide treatment. CONCLUSIONS: Taspoglutide promoted ß-cell proliferation, prevented apoptosis in vitro and exerted multiple ß-cell protective effects on islet architecture and function in vivo in ZDF rats.

Quality of life in adults with spinal cord injury living in the community.

STUDY DESIGN: The study design used is cross-sectional descriptive survey. OBJECTIVES: The aim of this study is to describe the subjective and objective quality of life (QoL) of adults with chronic non-traumatic spinal cord injury (NT-SCI) and to compare the objective and subjective QoL of adults with chronic NT-SCI with adults who have a chronic traumatic spinal cord injury (T-SCI) and the general population. SETTING: Living in the general community (non-residential care), Australia. PARTICIPANTS: The study included 443 adults with SCI (T-SCI, n=381) (NT-SCI, n=62), all SCI ≥6 months duration. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Objective and subjective QoL domains--Comprehensive QoL Scale for Adults, version 5 (COMQoL-A5); acceptance subscale--the Spinal Cord Lesion Coping Strategies Questionnaire, version 1 Australia (SCL CSQ v1.0 Australia). RESULTS: Despite demographic differences, only the objective QoL domain material (higher in NT-SCI) and the subjective QoL domain health (lower in NT-SCI) were significantly different between the SCI subgroups. In contrast, five of the seven objective domains and four of the seven subjective domains were significantly lower in the SCI sample as a whole, compared with the general population. Post hoc analyses suggested that aetiology of the SCI was not responsible for QoL differences within the cohort with SCI. CONCLUSION: On the whole, aetiology makes little difference to QoL outcomes after SCI. The QoL of adults with chronic T-SCI and NT-SCI fall significantly below that of the general population in most domains.

Taspoglutide, a novel human once-weekly analogue of glucagon-like peptide-1, improves glucose homeostasis and body weight in the Zucker diabetic fatty rat.

AIM: Glucagon-like peptide-1 (GLP-1) receptor agonists are a novel class of pharmacotherapy for type 2 diabetes. We investigated the effects of a novel, long-acting human GLP-1 analogue, taspoglutide, in the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. METHODS: Blood glucose and plasma levels of insulin, peptide YY (PYY), glucose-dependent insulinotropic polypeptide (GIP) and triglycerides were measured during oral glucose tolerance tests (oGTT) conducted in ZDF rats treated acutely or chronically with a single long-acting dose of taspoglutide. Pioglitazone was used as a positive control in the chronic study. Postprandial glucose, body weight, glycaemic control and insulin sensitivity were assessed over 21 days in chronically treated animals. RESULTS: Acute treatment with taspoglutide reduced glucose excursion and increased insulin response during oGTT. In chronically treated rats, glucose excursion and levels of GIP, PYY and triglycerides during oGTT on day 21 were significantly reduced. Postprandial glucose levels were significantly lower than vehicle controls by day 15. A significant reduction in body weight gain was noticed by day 8, and continued until the end of the study when body weight was approximately 7% lower in rats treated with taspoglutide compared to vehicle. Glycaemic control (increased levels of 1,5-anhydroglucitol) and insulin sensitivity (Matsuda index) were improved by taspoglutide treatment. CONCLUSIONS: Taspoglutide showed typical effects of native GLP-1, with improvement in glucose tolerance, postprandial glucose, body weight, glycaemic control and insulin sensitivity.

Comparison of depression, anxiety and stress in persons with traumatic and non-traumatic post-acute spinal cord injury.

STUDY DESIGN: Community cross-sectional self-report survey of adults with spinal cord injury (SCI). OBJECTIVES: The aim of this study was to examine the likelihood of depression, anxiety and stress in adults with non-traumatic SCI (NT-SCI) compared with adults with traumatic SCI (T-SCI). SETTING: Victoria, Australia. Adults (N=443; NT-SCI n=62) living in the community and attending specialist SCI rehabilitation clinics. METHODS: Participants completed a self-report survey by internet, telephone or hard copy. Items included demographic and injury-related characteristics and the short form Depression, Anxiety and Stress Scale (DASS-21). RESULTS: Persons with NT-SCI were significantly more likely to be female (P<0.05), older (P<0.001) and have lower-level incomplete injuries (P<0.001). The probability of depression, anxiety or stress in respondents with NT-SCI did not differ from persons with T-SCI (P>0.05). Overall, the prevalence of adverse mental health problems defined by scoring above DASS-21 cutoffs, were depression 37%, anxiety 30%, and clinically significant stress 25%. CONCLUSIONS: This study examined multiple mental health outcomes after NT-SCI in Australia. This study provides some evidence that the results of studies of depression, anxiety or stress in persons with T-SCI can be generalised to those with NT-SCI in the post-acute phase. NT-SCI patients are also at substantial risk of poor mental health outcomes. General demographic and injury-related characteristics do not seem to be important factors associated with the mental health of adults with SCI whether the SCI is traumatic or non-traumatic in origin.

Translation and Australian validation of the spinal cord lesion-related coping strategies and emotional wellbeing questionnaires.

STUDY DESIGN: Representative community cross-sectional self-report survey of adults with spinal cord injury (SCI). OBJECTIVES: To establish semantic translation and validation of the Swedish scales--the Spinal Cord Lesion Coping Strategies Questionnaire and the Spinal Cord Lesion Emotional Wellbeing Questionnaire. SETTING: Adults on the Victorian traumatic SCI register and attendees of the nontraumatic outpatient clinic were invited to participate. METHODS: Instruments were forward and backward translated to establish semantic equivalence. Principle components analyses were undertaken. Correlation and logistic regression analyses were conducted to demonstrate validity of the instruments using both positive (high quality of life) and negative (depression and anxiety) psychological outcomes. RESULTS: The final sample consisted of 443 adults with SCI living in the community. Both instruments demonstrated acceptable psychometric properties. Univariate correlation analyses showed most of the new scale components displayed medium to large relationships in the expected direction with the psychological outcomes and the other subscales. Health status and helplessness were significant predictors of both the positive and negative psychological outcomes in the logistic regression analyses. Acceptance was significantly related to the positive outcome only. Female and incomplete tetraplegia categories were significantly and positively related to depression only. CONCLUSION: Notwithstanding a few issues with some of the subscales, the results support the usefulness of these easy to use instruments and point to ways for further development of the scales.

Regioselective enzymatic diol esterification in batch and fixed-Bed adsorptive reactors: experiments and modeling.

The dynamic behavior of batch and fixed-bed adsorptive reactors is studied for the enzyme-catalyzed regioselective esterification of propionic acid and 2-ethyl-1,3-hexanediol in hexane. The reaction is equilibrium-limited with an apparent equilibrium constant of 0.6 +/- 0.1 at 22 degrees C. Moreover, accumulation of water produced in the reaction onto the biocatalyst causes a decrease in the catalytic activity. As a result, improvements in both reaction rate and final conversion can be achieved by operating in an adsorptive-reactor mode. Control of water in the reactor is achieved with a catalytically inert ion-exchange resin in Na-form. The resin prevents an excessive accumulation of water on the biocatalyst and reduces equilibrium limitations. The thermodynamic activity of water is identified as a key parameter for the design of such reactors. A mathematical model capable of predicting the water activity as a function of the varying concentrations of reactants and products is thus developed and found to successfully predict the experimental behavior observed in laboratory reactors. Substantial improvements in performance predicted by the model are seen experimentally in batch reactions and during the transient operation of continuous-flow fixed-bed reactors combining adsorptive and catalytic functions.

p53 tumour suppressor gene and RAS oncogenes: molecular analysis in the chronic and leukaemic phases of essential thrombocythaemia.

A panel of 51 cases of essential thrombocythaemia (ET), in chronic or leukaemic phase, was investigated for p53 gene and RAS oncogenes mutations by PCR-SSCP-direct sequencing. No RAS oncogenes mutations were detected, but p53 mutations were identified in three cases: 1/27 cases (approximately 4%) in chronic phase not undergoing chemotherapy, 1/19 cases (approximately 5%) in chronic phase undergoing chemotherapy, and 1/5 cases (20%) which had progressed to leukaemia. Our results suggest that: (1) p53 gene mutations occur sporadically in the chronic phase of ET, independent of chemotherapy, and may contribute to the progression to the leukaemic phase in a limited number of ET patients; (2) the RAS genes family does not seem to be involved in the pathogenesis of ET, unlike other bcr/abl negative chronic myeloproliferative diseases (CMPDs).

Anatomical organization of the spinal paths to the soleus and gastrocnemius muscles of the rat hind limb.

The anatomical organization of the motoneuronal columns of the soleus and lateral gastrocnemius muscle and of the related premotor interneurons was studied in rats, using the retrograde transneuronal transport of WGA-HRP. Motoneurons of the gastrocnemius muscle have a well-developed dendritic arborization which spreads into the transverse plane of the spinal cord extending to the intermediate region of the grey matter, while dendrites of the soleus muscle motoneurons spread mainly in the rosto-caudal plane, where they remain inside the border of the motoneuronal column and form small dendritic bundles, suggesting a coupling of neuronal activity as is to be expected in the motoneurons of a tonically active postural muscle such as the soleus. Gastrocnemial premotor interneurons are located close to the motoneuronal column, while the soleus premotor interneurons are scattered all over the ventral horn and intermediate grey. The number of labelled premotor interneurons is greater when the WGA-HRP is injected into the soleus muscle. In both cases, the premotor interneurons could be classified as four different types on the basis of the shape and size of the neuronal somata. The differences in the anatomical organization of the spinal paths to the gastrocnemius and soleus muscles reflect the different tasks performed by these two synergic muscles in normal motor behaviour: fast phasic activity by the gastrocnemius muscle, slow tonic anti-gravity activity by the soleus muscle.