Specialisation in physiotherapy: A mark of maturity

Have you gained postgraduate qualifications or been invited to lecture to other physiotherapists regarding your area of practice? Do your clients present for treatment of a particular condition or area of the body? Should you be able to claim that you specialise in that particular condition or region of the body (e.g. shoulder injuries or headaches)? What defines specialisation within physiotherapy? What is a Specialist Physiotherapist

Suboptimal Omega-3 Levels in Australian Adolescents

Design, Setting and Participants:A cross-sectional descriptive study of 251 apparently healthy adolescents (192 female, 59 male) aged 15-17 years, in year 11, from 10 schools within the Northern Sydney and Central Coast areas of New South Wales. Participants provided a morning non-fasting blood sample via finger-prick and written answers to specific demographic and lifestyle questions. Omega-3 index was calculated by adding %EPA and %DHA values in the whole blood. Equivalent erythrocyte omega-3 index values were obtained by using conversion factors (1.33 for EPA and 2.22 for DHA) from published erythrocyte/whole blood values. Main Outcome Measures: Quantitation of the individual, and estimation of the group average, blood omega-3 Index. Results:The blood omega-3 Index for this adolescent cohort ranged from 2.1-22.3 with a mean of 8.3±3.2, and median of 7.8. On average males had a higher omega-3 Index compared to females (10.5±3.7 vs 7.7±2.6, p8. Three percent had an Index of On average, adolescents from low or medium socioeconomic communities had a significantly lower omega-3 Index compared to those from higher socioeconomic neighbourhoods (mean difference=1.4, p=0.018). Overall 20% of boys and 17% of girls reported regularly taking omega-3 supplements. Regular use of omega-3 supplements was associated with a higher average omega-3 Index (9.8±3.7, n=44 compared to 8.0±3.0, n=203, p=0.001 in those not taking supplements). Conclusion:This study indicates that Australian adolescents, even when from advantaged homes, have a high probability of below optimum omega-3 levels. As reduced omega-3 levels are linked to conditions of public health concern such as diabetes, asthma and depression, targeted strategies to improve the omega-3 status in the childhood population may be warranted

The Relative Value of Measures of Omega-3 Index, Perceived Stress, Cortisol and Sleep Time in Identifying Depression Among a Cohort of Australian Adolescents

Objective: To assess the relative prognostic value of 11 variables including, omega-3, perceived stress, cortisol and sleep duration, in predicting adolescent depression. Design, Setting and Participants: A cross-sectional study of 444 healthy adolescents aged 16-18 years, from 10 schools within the Northern Sydney and Central Coast regions of New South Wales, Australia. Participants provided blood and saliva samples and completed questionnaires. Statistical classification methods were used to model the relationships between the predictors and depression. Main Outcome Measures: relative predictive value of each variable in correctly classifying depression. Results: 6% of boys and 9% of girls were categorised as experiencing severe to extremely severe depression. 4% of boys and 10% of girls were categorised as experiencing severe to extremely severe stress. The mean AM:PM cortisol for boys, 22±101, was higher than that of girls, 11±10. The average omega-3 index for boys, 10.5±3.7, was also higher than that of girls, 7.7±2.6. The average sleep duration of 7.8±1.1 hrs showed no gender differences. The best classification model identified perceived stress as the most significant predictor of depression followed by BMI and omega-3 index. Cortisol ratio was a significant discriminator for boys but not girls. When stress was excluded, shorter sleep duration became a significant discriminator in both boys and girls with waist to hip ratio providing further discrimination in girls only. Conclusion: The strongest predictor of depression in adolescents was perceived stress followed by higher BMI and lower omega-3 levels. These findings provide a rational basis for establishing program priorities for the prevention and treatment of adolescent depression

Vδ2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure.

Vδ2+ γδ T cells are semi-innate T cells that expand markedly following P. falciparum (Pf) infection in naïve adults, but are lost and become dysfunctional among children repeatedly exposed to malaria. The role of these cells in mediating clinical immunity (i.e. protection against symptoms) to malaria remains unclear. We measured Vδ2+ T cell absolute counts at acute and convalescent malaria timepoints (n = 43), and Vδ2+ counts, cellular phenotype, and cytokine production following in vitro stimulation at asymptomatic visits (n = 377), among children aged 6 months to 10 years living in Uganda. Increasing age was associated with diminished in vivo expansion following malaria, and lower Vδ2 absolute counts overall, among children living in a high transmission setting. Microscopic parasitemia and expression of the immunoregulatory markers Tim-3 and CD57 were associated with diminished Vδ2+ T cell pro-inflammatory cytokine production. Higher Vδ2 pro-inflammatory cytokine production was associated with protection from subsequent Pf infection, but also with an increased odds of symptoms once infected. Vδ2+ T cells may play a role in preventing malaria infection in children living in endemic settings; progressive loss and dysfunction of these cells may represent a disease tolerance mechanism that contributes to the development of clinical immunity to malaria

MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension

Rationale: The pathogenesis of PAH remains unclear. The four microRNAs representing the miR-143 and miR-145 stem loops are genomically clustered. Objective: To elucidate the transcriptional regulation of the miR-143/145 cluster, and the role of miR-143 in PAH. Methods and Results: We identified the promoter region that regulates miR-143/145 miRNA expression in pulmonary artery smooth muscle cells (PASMCs). We mapped PAH-related signalling pathways, including estrogens receptor (ER), liver X factor/retinoic X receptor (LXR/RXR), TGF-β (Smads), and hypoxia (HRE) that regulated levels of all pri-miR stem loop transcription and resulting miRNA expression. We observed that miR-143-3p is selectively upregulated compared to miR-143-5p during PASMC migration. Modulation of miR-143 in PASMCs significantly altered cell migration and apoptosis. In addition, we found high abundance of miR-143-3p in PASMCs-derived exosomes. Using assays with pulmonary arterial endothelial cells (PAECs) we demonstrated a paracrine pro-migratory and pro-angiogenic effect of miR-143-3p enriched exosomes from PASMC. Quantitative PCR and in situ hybridisation showed elevated expression of miR-143 in calf models of PAH as well as in samples from PAH patients. Moreover, in contrast to our previous findings that had not supported a therapeutic role in vivo, we now demonstrate a protective role for miR-143 in experimental PH in vivo in miR-143-/- and antimiR143-3p-treated mice exposed to chronic hypoxia in both preventative and reversal settings. Conclusions: MiR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while inhibition of miR-143-3p blocked experimental PH. Taken together these findings confirm an important role for the miR-143/145 cluster in PAH pathobiology

New Insights into Bacterial Chemoreceptor Array Structure and Assembly from Electron Cryotomography

Bacterial chemoreceptors cluster in highly ordered, cooperative, extended arrays with a conserved architecture, but the principles that govern array assembly remain unclear. Here we show images of cellular arrays as well as selected chemoreceptor complexes reconstituted in vitro that reveal new principles of array structure and assembly. First, in every case, receptors clustered in a trimers-of-dimers configuration, suggesting this is a highly favored fundamental building block. Second, these trimers-of-receptor dimers exhibited great versatility in the kinds of contacts they formed with each other and with other components of the signaling pathway, although only one architectural type occurred in native arrays. Third, the membrane, while it likely accelerates the formation of arrays, was neither necessary nor sufficient for lattice formation. Molecular crowding substituted for the stabilizing effect of the membrane and allowed cytoplasmic receptor fragments to form sandwiched lattices that strongly resemble the cytoplasmic chemoreceptor arrays found in some bacterial species. Finally, the effective determinant of array structure seemed to be CheA and CheW, which formed a “superlattice” of alternating CheA-filled and CheA-empty rings that linked receptor trimers-of-dimer units into their native hexagonal lattice. While concomitant overexpression of receptors, CheA, and CheW yielded arrays with native spacing, the CheA occupancy was lower and less ordered, suggesting that temporal and spatial coordination of gene expression driven by a single transcription factor may be vital for full order, or that array overgrowth may trigger a disassembly process. The results described here provide new insights into the assembly intermediates and assembly mechanism of this massive macromolecular complex

Exercise prescription improves exercise tolerance in young children with CHD:a randomised clinical trial

Objective The main objective of this study was to ascertain if a structured intervention programme can improve the biophysical health of young children with congenital heart disease (CHD). The primary end point was an increase in measureable physical activity levels following the intervention.Methods Patients aged 5–10 years with CHD were identified and invited to participate. Participants completed a baseline biophysical assessment, including a formal exercise stress test and daily activity monitoring using an accelerometer. Following randomisation, the intervention group attended a 1 day education session and received an individual written exercise plan to be continued over the 4-month intervention period. The control group continued with their usual level of care. After 4 months, all participants were reassessed in the same manner as at baseline.Results One hundred and sixty-three participants (mean age 8.4 years) were recruited, 100 of whom were male (61.3%). At baseline, the majority of the children were active with good exercise tolerance. The cyanotic palliated subgroup participants, however, were found to have lower levels of daily activity and significantly limited peak exercise performance compared with the other subgroups. One hundred and fifty-two participants (93.2%) attended for reassessment. Following the intervention, there was a significant improvement in peak exercise capacity in the intervention group. There was also a trend towards increased daily activity levels.Conclusion Overall physical activity levels are well preserved in the majority of young children with CHD. A structured intervention programme significantly increased peak exercise capacity and improved attitudes towards positive lifestyle changes

FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure.

Exposure to Plasmodium falciparum is associated with circulating "atypical" memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum