NUCEL (Cell and Molecular Therapy Center): A multidisciplinary center for translational research in Brazil

Social and economical development is closely associated with technological innovation and a well-developed biotechnological industry. In the last few years, Brazil`s scientific production has been steadily increasing; however, the number of patents is lagging behind, with technological and translational research requiring governmental incentive and reinforcement. The Cell and Molecular Therapy Center (NUCEL) was created to develop activities in the translational research field, addressing concrete problems found in biomedical and veterinary areas and actively searching for solutions by employing a genetic engineering approach to generate cell lines over-expressing recombinant proteins to be transferred to local biotech companies, aiming at furthering the development of a national competence for local production of biopharmaceuticals of widespread use and of life-saving importance. To this end, mammalian cell engineering technologies were used to generate cell lines over-expressing several different recombinant proteins of biomedical and biotechnological interest, namely, recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX clotting factors for hemophilia, human and bovine FSH for fertility and reproduction, and human bone repair proteins (BMPs). Expression of some of these proteins is also being sought with the baculovirus/insect cell system (BEVS) which, in many cases, is able to deliver high-yield production of recombinant proteins with biological activity comparable to that of mammalian systems, but in a much more cost-effective manner. Transfer of some of these recombinant products to local Biotech companies has been pursued by taking advantage of the Sao Paulo State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for joint Research Development and Innovation partnership projects.

Keratinocyte growth factor: a new mesothelial targeted therapy to reduce postoperative pericardial adhesions

Background: Several methods have been utilized to prevent pericardial and retrosternal adhesions, but none of them evaluated the mesothelial regenerative hypothesis. There are evidences that the mesothelial trauma reduces pericardial fibrinolytic capability and induces an adhesion process. Keratinocyte growth factor (KGF) has proven to improve mesothelial cells proliferation. This study investigated the influence of keratinocyte growth factor in reducing post-surgical adhesions. Methods: Twelve pigs were operated and an adhesion protocol was employed. Following a stratified randomization, the animals received a topical application of KGF or saline. At 8 weeks, intrapericardial adhesions were evaluated and a severity score was established. The time spent to dissect the adhesions and the amount of sharp dissection used, were recorded. Histological sections were stained with sirius red and morphometric analyses were assessed with a computer-assisted image analysis system. Results: The severity score was lower in the KGF group than in the control group (11.5 vs 17, p = 0.005). The dissection time was lower in the KGF group (9.2 +/- 1.4 min vs 33.9 +/- 9.2 min, p = 0.004) and presented a significant correlation with the severity score (r = 0.83, p = 0.001). A significantly less sharp dissection was also required in the KGF group. Also, adhesion area and adhesion collagen were significantly tower in the KGF group than in the control group. Conclusion: The simulation of pericardial cells with KGF reduced the intensity of postoperative adhesions and facilitated the re-operation. This study suggests that the mesothelial regeneration is the new horizon in anti-adhesion therapies. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

A therapy dog's impact on daytime activity and night-time sleep for older persons with Alzheimer's disease : a case study

Background: Animal-Assisted Therapy using dogs have been described as having a calming effect, decrease sundowning and blood-pressure in persons with Alzheimer’s disease. The aim was to investigate how continuous and scheduled visits by a prescribed therapy dog affected daytime and night-time sleep for persons with Alzheimer’s disease. Methods: In this case study, registration of activity and sleep curves was conducted from five persons with moderate to severe Alzheimer’s disease living at a nursing home, over a period of 16 weeks using an Actiwatch. Data was analysed with descriptive statistics. Result: The study shows no clear pattern of effect on individual persons daytime activity and sleep when encounter with a therapy dog, but instead points to a great variety of possible different effects that brings an increased activity at different time points, for example during night-time sleep. Conclusions: Effects from the use of a Animal-Assisted Therapy with a dog in the care of persons with Alzheimer’s disease needs to be further investigated and analysed from a personcentred view including both daytime and nightime activities.

Can therapy dogs evoke awareness of one's past and present life in persons with Alzheimer's disease?

BACKGROUND: Persons with Alzheimer's disease (AD) sometimes express themselves through behaviours that are difficult to manage for themselves and their caregivers, and to minimise these symptoms alternative methods are recommended. For some time now, animals have been introduced in different ways into the environment of persons with dementia. Animal-Assisted Therapy (AAT) includes prescribed therapy dogs visiting the person with dementia for a specific purpose. AIM: This study aims to illuminate the meaning of the lived experience of encounters with a therapy dog for persons with Alzheimer's disease. METHOD: Video recorded sessions were conducted for each visit of the dog and its handler to a person with AD (10 times/person). The observations have a life-world approach and were transcribed and analysed using a phenomenological hermeneutical approach. RESULTS: The result shows a main theme 'Being aware of one's past and present existence', meaning to connect with one's senses and memories and to reflect upon these with the dog. The time spent with the dog shows the person recounting memories and feelings, and enables an opportunity to reach the person on a cognitive level. CONCLUSIONS: The present study may contribute to health care research and provide knowledge about the use of trained therapy dogs in the care of older persons with AD in a way that might increase quality of life and well-being in persons with dementia. IMPLICATIONS FOR PRACTICE: The study might be useful for caregivers and dog handlers in the care of older persons with dementia.

Evaluation of a cognitive behavior therapy program for people with sexual dysfunction

This article reports on an evaluation of a cognitive behavioral program for the treatment of sexual dysfunction. Frequency data are provided on the sexual dysfunction of 95 males (mean age = 41.6 years) and 105 females (mean age = 36.4 years). The effectiveness of a cognitive behavioral program among 45 sexually dysfunctional males (mean age = 39.9 years) and 54 sexually dysfunctional females (mean age = 36.2 years) was assessed. The results demonstrated that, after therapy, respondents experienced lower levels of sexual dysfunction, more positive attitudes toward sex, perceptions that sex was more enjoyable, fewer affected aspects of sexual dysfunction in their relationship, and a lower likelihood of perceiving themselves as a sexual failure. The implications of these findings for the treatment of sexual dysfunction are discussed.

"I will start treatment when I think the time is right":HIV-positive gay men talk about their decision not to access antiretroviral therapy.

In a qualitative study, 20 HIV-infected Australian gay men were interviewed about their decision not to access antiretroviral drug therapy. The main reasons given for the decision were fear of side effects; fear of long-term damage to body organs; the inconvenience of the treatment regimens; belief that the regimen's demands would be a threat to morale; and belief that there was no reason to start therapy in the absence of AIDS-related symptoms. Actions taken by the men to monitor and maintain their health included seeing a doctor regularly; having regular T-cell and viral load tests; and trying to maintain a positive outlook by not letting HIV/AIDS 'take over' their lives. Almost half the men considered they had been subjected to unreasonable pressure to access therapy and there was considerable pride at having resisted this pressure. The findings suggest that the men disagreed with the biomedical model for managing HIV/AIDS only on the question of if and when to access therapy. They also suggest that underlying the men's dissent from the biomedical model was a different mode of thinking than is required by the model: while the model demands thinking that is abstract, the men focused strongly on factors close to the 'here and now' of immediate experience. The practical implications of the findings are explored.

The meaning of professional excellence for private practitioners in occupational therapy

OT AUSTRALIA's Accredited Occupational Therapist Program is promoted using the message 'Assuring professional excellence'. It is widely assumed that professional excellence is understood. Yet, this concept encompasses complex themes, including competence and clinical reasoning. In this paper, the meaning of professional excellence is examined by investigating the perspectives of private practitioners. Private practitioners were chosen as they represent the diversity of the occupational therapy field, and may pre-empt trends within broader practice. Sixteen key informants were interviewed to obtain their perspectives on professional excellence. Common themes that arose from the findings include the significance of experience in practice, and the importance of understanding one's limitations in knowledge and expertise. Findings are discussed in relation to OT AUSTRALIA's aim to assure standards of practice.

Outdoor education and bush adventure therapy: A social-ecological approach to health and wellbeing.

Together, outdoor education and bush adventure therapy can be seen to constitute a population-wide health intervention strategy. Whether in educational or therapeutic settings, the intentional use of contact with nature, small groups, and adventure provides a unique approach in the promotion of health and wellbeing for the general population, and for individuals with identified health vulnerabilities. This paper explicitly emphasises human and social health, however, an integral assumption is that a healthy and sustainable environment is dependent on healthy human relationships with nature. We invite outdoor educators and bush adventure therapy practitioners to examine the proposition that healthy interactions with nature can create a unique stream of socio-ecological interventions. A spectrum of outdoor adventure programs is provided, allowing outdoor educators and bush adventure therapy practitioners to locate their work according to program context and aims, and participant aims and needs.

Reality therapy and the human energy field : working with needs that influence mind and body

There is accumulating evidence that body and mind, or rather the physical and the non-physical, are intrinsically connected. The mechanisms through which reality therapy works on mind and body may be explained via positive dynamics in the central nervous system, the body's biochemistry and the human energy field. The purpose of this paper is to show the relationship between choice theory and the nature of the power centers in the human energy field. Understanding the drivers behind human behavior and facilitating the choice to think realistically and to make responsible choices assists wholeness and enhances the physical, mental and spiritual health.

Professional competence for private practitioners in occupational therapy

The aim of the present study was to investigate the meaning of professional competence for occupational therapy private practitioners and their experience of the barriers to professional competence. Semi-structured interviews with 16 key informants from private practice in Victoria elicited diverse opinions and experiences. However, the difficulty of assessing competence, and the lack of standards that identify competent practice for occupational therapy were major themes in the findings. The role of theory in competent practice was evident in discussion but it was not clearly articulated by many participants. Experiences of professional socialisation varied yet participants perceived input from peers as contributing to assuring competence. Major barriers to professional competence were identified as professional isolation, time and finances. The present study highlights the complexity of current attempts to assess professional competence for practising occupational therapists including the implementation of an accreditation program by The Australian Association of Occupational Therapists Inc. (OT AUSTRALIA), the peak body representing occupational therapists.

Will he get back to normal? survival and functional status after intensive care therapy

The study aim was to address healthcare workers’ and patients’ questions about the likely level of recovery at 6 months of patients admitted to an Australian intensive care unit (ICU). Ninety-three consecutive, eligible adults were identified and followed prospectively. Severity of illness on admission was assessed using Acute Physiological and Chronic Health Evaluation (APACHE II), while functional status at 6 months was evaluated using the Sickness Impact Profile (SIP). Cumulative mortality was 25%. Admission severity of illness was associated with survival at 6 months (P≤0.001). Fifty-one (78%) of the 70 survivors were interviewed. Admission severity of illness scores correlated with functional status at 6 months (r=0.34, P=0.01), a finding reported in only one other study. More than half of those interviewed had returned to near pre-admission functional status. Those with poor functional status included high proportions of people with chronic illness and head injury. Overall, physical recovery was more complete than psychosocial recovery. The findings provide useful information for addressing questions relating to physical and psychosocial recovery, appetite, sleep patterns and return to work post discharge.

Testosterone replacement therapy-perceptions of recipients and partners

Background. The androgenic hormones are important determinants of sexual behaviour in men. Testosterone replacement is important treatment for pituitary disease to maintain normal functioning. Although the physical effects of testosterone replacement have been well documented, little is known about the effects on relationships, particularly from the point of view of the sexual partners of men receiving testosterone replacement.

Aims. This paper reports a study exploring the perceptions of testosterone replacement on well-being and sexual functioning.

Methods. Semi-structured interviews were conducted with five men receiving testosterone implants (recipients), their permanent partners, and five recipients without partners. Recipient serum testosterone concentration was measured at 0, 1 and 4 months after testosterone implantation.

Results. The three groups reported similar effects of testosterone on well-being and sexual functioning. Recipient and partner ratings were also similar. Strength was less affected by decreasing testosterone concentration than energy in men with partners, but both strength and energy declined in men without partners. Decreased testosterone levels had a statistically significantly different effect on libido at time zero between men with and without partners (P < 0·015) and on ability to sustain an erection, but the ability to achieve an erection persisted over the 6 months in both male groups. Intercourse frequency increased from once per week at time 0 to ≥3 per week between 1 and 4 months after implant in men with partners. There were important effects of testosterone deficiency on general and sexual relationships, and these differed between men with partners and those without.

Conclusions. Testosterone has important physical and psychological benefits that may be related to the age at which testosterone replacement commences and the indications for its use. The small sample size may limit the ability to generalize the findings outside the study.

Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy

Objective: To assess the evidence for the effectiveness of increasing numbers of drugs in antiretroviral combination therapy.

Design: Systematic review, meta-analysis, and meta-regression of fully reported randomised controlled trials. All studies included compared quadruple versus triple therapy, triple versus double therapy, double versus monotherapy, or monotherapy versus placebo or no treatment.

Participants: Patients with any stage of HIV infection who had not received antiretroviral therapy.

Main outcome measures: Changes in disease progression or death (clinical outcomes); CD4 count and plasma viral load (surrogate markers).
Search strategy: Six electronic databases, including Medline, Embase, and the Cochrane Library, searched up to February 2001.

Results: 54 randomised controlled trials, most of good quality, with 66 comparison groups were included in the analysis. For both the clinical outcomes and surrogate markers, combinations with up to and including three (triple therapy) were progressively and significantly more effective. The odds ratio for disease progression or death for triple therapy compared with double therapy was 0.6 (95% confidence interval 0.5 to 0.8). Heterogeneity in effect sizes was present in many outcomes but was largely related to the drugs used and trial quality.

Conclusions: Evidence from randomised controlled trials supports the use of triple therapy. Research is needed on the effectiveness of quadruple therapies and the relative effectiveness of specific combinations of drugs.

Cost-effectiveness of cognitive-behavioural therapy and drug interventions for major depression

Objective: Antidepressant drugs and cognitive–behavioural therapy (CBT) are effective treatment options for depression and are recommended by clinical practice guidelines. As part of the Assessing Cost-effectiveness – Mental Health project we evaluate the available evidence on costs and benefits of CBT and drugs in the episodic and maintenance treatment of major depression.

Method: The cost-effectiveness is modelled from a health-care perspective as the cost per disability-adjusted life year. Interventions are targeted at people with major depression who currently seek care but receive non-evidence based treatment. Uncertainty in model inputs is tested using Monte Carlo simulation methods.

Results: All interventions for major depression examined have a favourable incremental cost-effectiveness ratio under Australian health service conditions. Bibliotherapy, group CBT, individual CBT by a psychologist on a public salary and tricyclic antidepressants (TCAs) are very cost-effective treatment options falling below $A10 000 per disability-adjusted life year (DALY) even when taking the upper limit of the uncertainty interval into account. Maintenance treatment with selective serotonin re-uptake inhibitors (SSRIs) is the most expensive option (ranging from $A17 000 to $A20 000 per DALY) but still well below $A50 000, which is considered the affordable threshold.

Conclusions: A range of cost-effective interventions for episodes of major depression exists and is currently underutilized. Maintenance treatment strategies are required to significantly reduce the burden of depression, but the cost of long-term drug treatment for the large number of depressed people is high if SSRIs are the drug of choice. Key policy issues with regard to expanded provision of CBT concern the availability of suitably trained providers and the funding mechanisms for therapy in primary care.