‘I learned more than from any lecture’ – Indigenous place and space for teaching Indigenous health to physiotherapy students

Background: Australian Indigenous health remains inequitable on a number of health outcomes compared to non-Indigenous Australians. Preventable chronic conditions make up a large proportion of the ‘gap’ in Indigenous health. Physiotherapists have expertise in the management of such conditions and health promotion in the areas of physical activity, pain and symptom management, managing the impact of co-morbidities and promoting self-management. However, there is little published literature regarding effective approaches of teaching Indigenous health to entry-to-practice physiotherapy students.

Objectives: This paper offers insights from an innovative Indigenous pedagogical approach for second year Doctor of Physiotherapy students at the University of Melbourne that explores indigenized place and space in the teaching of Indigenous health.

Major findings: Student feedback indicated that aspects of the session were effective in the context of ‘a productive tension’ evidenced by insightful, constructive, and empathic reflections.

Conclusions: A demonstrated willingness by students to engage with an indigenized place and to engage with the ‘tension’ indicated the shift required in the physiotherapy academic space.     

Stimulation of non-parietal cell secretion in canine Heidenhain pouches by 16,16-dimethyl prostaglandin E2

The permeability effects of topical and intravenous prostaglandin E2 (PGE2) and 16,16-dimethyl prostaglandin E2 (16DM) were studied in canine Heidenhain pouches using an acid-free perfusate, and changes in volume and HCO-3 content of the perfusate were measured. Topical and intravenous 16DM increased the apparent flux of Na+ and Cl-, and stimulated the secretion of fluid containing HCO-3. 16DM stimulates non-parietal cell secretion and therefore the movement of Na+ cannot be interpreted as passive flux in response to changes in permeability.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Survival analysis in percutaneous endoscopic gastrostomy feeding: a worse outcome in patients with dementia

OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) feeding has been validated in specific clinical situations such as acute stroke with dysphagia and oropharyngeal malignancy. The perception that gastrostomy insertion is safe and technically simple has led to an increase in the demands for PEG insertion, encompassing clinical applications such as in patients with dementia, in whom its role has not been justified. The purpose of this study was to compare the mortality of patients with dementia who were fed by PEG to that of other subgroups of patients requiring gastrostomy feeding. METHODS: The study focused on a cohort of 361 consecutive patients requiring PEG feeding between August 1992 and July 1997 from two District General Hospitals (Rotherham District General Hospital and Doncaster Royal Infirmary) in South Yorkshire. A retrospective cohort survival analysis was performed using the Kaplan-Meier survival method and Cox proportional hazards analysis. RESULTS: In all patients requiring gastrostomy feeding there is a high initial mortality of 28% at 30 days. However, patients with dementia have a worse prognosis compared to other subgroups, with 54% having died at 1 month and 90% at 1 yr (log rank test p < 0.0001). This difference remained significant (log rank p < 0.0001) after adjusting for age at the time of PEG insertion. CONCLUSIONS: This is the first demonstration in the United Kingdom that the mortality of patients with dementia who are fed by gastrostomy is considerable. Consequently, we may wish to advise against gastrostomy feeding in selected patients within this clinical setting.     

Additional methadone increases craving for heroin: a double-blind, placebo-controlled study of chronic opiate users receiving methadone substitution treatment

Aims. To assess the acute-on-chronic effects of methadone on drug craving, mood and cognitive and psychomotor functioning in patients on long-term methadone substitution treatment. Design and participants. A double-blind, cross-over design was used to compare the effects of a 33% increase in patient's daily dosage of methadone with a matched placebo linctus. Eighteen patients completed the study; all were assessed pre- and post-drug on two separate testing days. Findings. Methadone significantly increased both positive craving (expected positive effects) and negative craving (expected relief of withdrawal discomfort) for heroin. Patients were unable to distinguish between methadone and placebo treatments. No differences between treatments emerged in cognitive or psychomotor effects. In terms of mood, patients were more alert and more contented following placebo than following methadone. Conclusions. Additional methadone may "prime" cravings for heroin in methadone substitution patients.     

Effects of TSH receptor mutations on binding and biological activity of monoclonal antibodies and TSH.

The effects of an extensive series of mutations in the TSH receptor (TSHR) leucine-rich domain (LRD) on the ability of thyroid-stimulating monoclonal antibodies (TSMAbs) and TSH to bind to the receptor and stimulate cyclic AMP production in TSHR-transfected CHO cells has been investigated. In addition, the ability of a mouse monoclonal antibody with blocking (i.e., antagonist) activity (RSR-B2) to interact with mutated receptors has been studied. Several amino acids distributed along an extensive part of the concave surface of the LRD were found to be important for binding and stimulation by the thyroid-stimulating human MAb M22 but did not appear to be important for TSH binding and stimulation. Most of these amino acids important for M22 interactions were also found to be important for the stimulating activity of six different mouse TSMAbs and a hamster TSMAb. Furthermore, most of these same amino acids were important for stimulation by TSHR autoantibodies in a panel of sera from patients with Graves' disease. Amino acid R255 was the only residue found to be unimportant for TSH stimulation but critical for stimulation by all thyroid-stimulating antibodies tested (23 patient serum TSHR autoantibodies, M22, and all seven animal TSMAbs). About half the amino acids (all located in the N-terminal part of the LRD) found to be important for M22 activity were also important for the blocking activity of RSR-B2 and although the epitopes for the two MAbs overlap they are different. As the two MAbs have similar affinities, their epitope differences are probably responsible for their different activities. Overall our results indicate that different TSMAbs and different patient sera thyroid-stimulating autoantibodies interact with the same region of the TSHR, but there are subtle differences in the actual amino acids that make contact with the different stimulators.     

Ultra‐deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Assessing trauma and related distress in refugee youth and their caregivers: should we be concerned about iatrogenic effects?

Assessment of potentially traumatic events and related psychological symptoms in refugee youth is common in epidemiological and intervention research. The objective of this study is to characterize reactions to assessments of trauma exposure and psychological symptoms, including traumatic stress, in refugee youth and their caregivers. Eighty-eight Somali youth and their caregivers participated in a screening and baseline interview for a psychological intervention in three refugee camps in Ethiopia. Participants were asked about their levels of distress prior to, immediately after, and approximately two weeks after completing the interview. Other quantitative and qualitative questions inquired about specific reactions to interview questions and procedures. Children and caregivers became increasingly relaxed over the course of the interview, on average. Few children (5.3%) or caregivers (6.5%) who reported being relaxed at the beginning of the interview became upset by the end of the interview. Some children and caregivers reported that certain assessment questions were upsetting and that feeling upset interfered with their activities. Despite some participants reporting persistent negative reactions, most reported liking and benefitting from the interview. While the majority of refugee youth and their caregivers reported positive experiences associated with completing trauma-related assessments, some reported negative reactions. Researchers and practitioners must consider the necessity, risks, and benefits of including questions about potentially traumatic events and related symptoms that are particularly upsetting in screening, survey research, and clinical assessment. When included, it is important that researchers and practitioners monitor negative reactions to these assessments and connect participants who become distressed with appropriate services.