Effects of aerobic exercise therapy and cognitive behavioural therapy on functioning and quality of life in amyotrophic lateral sclerosis: protocol of the FACTS-2-ALS trial

Background

Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain.

Methods

We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles.

Results

Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91%) and acceptable specificity (70%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct.

Conclusions

The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.     

SEPALLATA3: the 'glue' for MADS box transcription factor complex formation

Background  

Plant MADS box proteins play important roles in a plethora of developmental processes. In order to regulate specific sets of target genes, MADS box proteins dimerize and are thought to assemble into multimeric complexes. In this study a large-scale yeast three-hybrid screen is utilized to provide insight into the higher-order complex formation capacity of the Arabidopsis MADS box family. SEPALLATA3 (SEP3) has been shown to mediate complex formation and, therefore, special attention is paid to this factor in this study.     

Doctors on Status and Respect: A Qualitative Study

While doctors generally enjoy considerable status, some believe that this is increasingly threatened by consumerism, managerialism, and competition from other health professions. Research into doctors’ perceptions of the changes occurring in medicine has provided some insights into how they perceive and respond to these changes but has generally failed to distinguish clearly between concerns about “status,” related to the entitlements associated with one’s position in a social hierarchy, and concerns about “respect,” related to being held in high regard for one’s moral qualities. In this article we explore doctors’ perceptions of the degree to which they are respected and their explanations for, and responses to, instances of perceived lack of respect. We conclude that doctors’ concerns about loss of respect need to be clearly distinguished from concerns about loss of status and that medical students need to be prepared for a changing social field in which others’ respect cannot be taken for granted.     

Marginalizing Experience: A Critical Analysis of Public Discourse Surrounding Stem Cell Research in Australia (2005�C6)

Over the past decade, stem cell science has generated considerable public and political debate. These debates tend to focus on issues concerning the protection of nascent human life and the need to generate medical and therapeutic treatments for the sick and vulnerable. The framing of the public debate around these issues not only dichotomises and oversimplifies the issues at stake, but tends to marginalise certain types of voices, such as the women who donate their eggs and/or embryos to stem cell research and the patients who might benefit from its potential clinical outcomes. This paper draws on empirical research conducted on a recent stem cell policy episode in Australia. From the qualitative examination of 109 newspaper opinion editorials and twenty-three in-depth interviews, it is argued that these voices are marginalised because they are based on discourses that have less epistemological status in public debate. Our results suggest that the personal experiences of women and patients are marginalised by the alliances that form between more powerful discourse communities that use science as a source of authority and legitimation. It is argued that members of these communities establish legitimacy and assert authority in public debate by discursively deploying science in claims that marginalise other epistemologies. Implications are discussed along with suggestions for a more enriched and inclusive public debate.     

Gifts, Drug Samples, and other Items Given to Medical Specialists by Pharmaceutical Companies

Aim  To ascertain the quantity and nature of gifts and items provided by the pharmaceutical industry in Australia to medical specialists and to consider whether these are appropriate in terms of justifiable ethical standards, empirical research and views expressed in the literature.Design and Setting  Fifty-one medical Sydney specialists were asked to collect all gifts, offers, invitations, and items received from pharmaceutical companies in an eight-week period.Main Outcome Measures  The items received were categorised as promotional/educational, drug samples, clinical practice aids, office gifts, personal gifts, and invitations; and were analysed in relation to the pharmaceutical industry Code of Conduct.Results  A large number (mean = 42/participant) and wide range of gifts and items were received. These included promotional/educational items (mean = 21), drug samples (mean = 8), office gifts (mean = 5) and personal gifts (mean = 1), clinical aids (mean = 3), and invitations (mean = 3) to meals, meetings, and conferences. Most gifts and items complied with the Code with a few breaches including offers of entertainment (sporting event and cabaret), items of high monetary value (in competitions with prizes unrelated to medicine), unbranded gifts, and promotional documents presented as journal articles.Conclusions  Medical specialists received many gifts and items from pharmaceutical companies and a few that infringed the Code current at the time of the study. The findings were considered in the light of changes that have since been made to the industry Code of Conduct and professional medical guidelines on ethical relationships between physicians and the industry. In large measure, these changes are supported although some suggestions are made for stricter standards.Competing Interest  Graham Macdonald is employed by Merck Sharp & Dohme (Australia). Richard Day serves as an Advisory Board member for Merck Sharp & Dohme (Australia) (rofecoxib, etoricoxib), Merck Sharp & Dohme (Asia) (rofecoxib), Abbott Australia (adalimumab), Schering–Plough Australia (infliximab), Amgen Australia (anakinra), GlaxoSmithKline Consumer Australia (paracetamol) and, previously, Pfizer Australia (celecoxib). Any honoraria for these activities are placed in audited trust funds of St Vincent’s Hospital, Sydney, to be used to support academic activities within the Department of Clinical Pharmacology.     

Direct interaction between Teashirt and Sex combs reduced proteins, via Tsh's acidic domain, is essential for specifying the identity of the prothorax in Drosophila

teashirt (tsh) encodes a zinc-finger protein that is thought to be part of a network that contributes to regionalization of the Drosophila embryo and establishes the domains of Hox protein function. tsh and the Hox gene Sex combs reduced (Scr) are essential to establish the identity of the first thoracic segment. We used the development of the first thoracic segment as a paradigm for Scr dependent regional morphological distinctions. In this specific context, we asked whether Tsh protein could have a direct influence on Scr activity. Here we present evidence that Tsh interacts directly with Scr and this interaction depends in part on the presence of a short domain located in the N-terminal half of Teashirt called "acidic domain". In vivo, expression of full length Tsh can rescue the tsh null phenotype throughout the trunk whereas Tsh lacking the Scr interacting domain rescues all the trunk defects except in the prothorax. We suggest this provides insights into the mechanism by which Tsh, in concert with Scr, specifies the prothoracic identity.     

Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

Background  

Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.     

Case Study: Polycystic Livers in a Transgenic Mouse Line

Three mice (2 male, 1 female; age, 5 to 16 mo) from a mouse line transgenic for keratin 14 (K14)-driven LacZ expression and on an outbred Crl:CD1(ICR) background, were identified as having distended abdomens and livers that were diffusely enlarged by numerous cysts (diameter, 0.1 to 2.0 cm). Histopathology revealed hepatic cysts lined by biliary type epithelium and mild chronic inflammation, and confirmed the absence of parasites. Among 21 related mice, 5 additional affected mice were identified via laparotomy. Breeding of these 5 mice (after 5 mo of age) did not result in any offspring; the K14 mice with polycystic livers failed to reproduce. Affected male mice had degenerative testicular lesions, and their sperm was immotile. Nonpolycystic K14 control male mice bred well, had no testicular lesions, and had appropriate sperm motility. Genetic analysis did not identify an association of this phenotype with the transgene or insertion site.Abbreviations: K14, keratin 14 promoter; LacZ, bacterial β-galactosidase LacZ reporter; Lsamp, mouse limbic system-associated membrane proteinPolycystic disease is a multiorgan disorder and is the most common genetic life-threatening disease in people, affecting more than 600,000 Americans.¹⁶ Cystic liver disease in people typically is associated with polycystic kidney disease^22,36 but can exist in its absence. Currently, 2 autosomal dominant genes (PRKCSH and SEC63P) that cause a human polycystic liver disease condition without renal involvement have been identified.^4-6,13Numerous rodent models of polycystic kidneys with concurrent polycystic liver exist.^8,34,39,40 However, effective models of polycystic liver without polycystic kidneys would be useful to address clinical and mechanistic issues of polycystic liver not associated with polycystic kidneys.^6,31Here we report multiple cases of a spontaneous polycystic liver phenotype without a kidney phenotype in a transgenic mouse line. We also describe the effect of the transgene on disease expression and our attempts to develop this stock as an animal model.