Systemic Family Therapy for Families who have Experienced Trauma: A Randomised Controlled Trial

This paper describes a randomised controlled trial (RCT) investigation of the added value of systemic family therapy (SFT) over individually focused cognitive behavioural therapy (CBT) for families in which one or more members has suffered trauma and been referred to a community-based psychotherapy centre. The results illustrate how an apparently robust design can be confounded by high attrition rates, low average number of therapeutic sessions and poor protocol adherence. The paper highlights a number of general and specific lessons regarding the resources and processes involved that can act as a model for those planning to undertake studies of this type and scope. A key message is that the challenges of conducting RCTs in ‘real world’ settings should not be underestimated. The wider implications in relation to the place of RCTs within the creation of the evidence base for complex psycho-social interventions is discussed and the current movement towards a phased mixed-methods approach, including the appropriate use of RCTs, which some might argue is a return to the original vision of evidence-based practice (EBP), is affirmed.

Colour Doppler ultrasound of the ocular circulation in patients with systemic lupus erythematosus identifies altered microcirculatory haemodynamics

We assessed whether quantitative analysis of Doppler flow velocity waveforms is able to identify subclinical microvascular abnormalities in SLE and whether eigenvector analysis can detect changes not detectable using the resistive index (RI). Fifty-four SLE patients with no conventional cardiovascular risk factors, major organ involvement or retinopathy were compared to 32 controls. Flow velocity waveforms were obtained from the ophthalmic artery (OA), central retinal artery (CRA) and common carotid artery (CA). The waveforms were analysed using eigenvector decomposition and compared between groups at each arterial site. The RI was also determined. The RI was comparable between groups. In the OA and CRA, there were significant differences in the lower frequency sinusoidal components (P <0.05 for each component). No differences were apparent in the CA between groups. Eigenvector analysis of Doppler flow waveforms, recorded in proximity of the terminal vascular bed, identified altered ocular microvascular haemodynamics in SLE. Altered waveform structure could not be identified by changes in RI, the traditional measure of downstream vascular resistance. This analytical approach to waveform analysis is more sensitive in detecting preclinical microvascular abnormalities in SLE. It may hold potential as a useful tool for assessing disease activity, response to treatment, and predicting future vascular complications.

Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation

The hypoxia-inducible factors (HIFs; isoforms HIF-1 alpha, HIF-2 alpha, HIF-3 alpha) mediate many responses to hypoxia. Their regulation is principally by oxygen-dependent degradation, which is initiated by hydroxylation of specific proline residues followed by binding of von Hippel-Lindau (VHL) protein. Chuvash polycythemia is a disorder with elevated HIF. It arises through germline homozygosity for hypomorphic VHL alleles and has a phenotype of hematological, cardiopulmonary, and metabolic abnormalities. This study explores the phenotype of two other HIF pathway diseases: classic VHL disease and HIF-2 alpha gain-of-function mutation. No cardiopulmonary abnormalities were detected in classic VHL disease. HIF-2 alpha gain-of-function mutations were associated with pulmonary hypertension, increased cardiac output, increased heart rate, and increased pulmonary ventilation relative to metabolism. Comparison of the HIF-2 alpha gain-of-function responses with data from studies of Chuvash polycythemia suggested that other aspects of the Chuvash phenotype were diminished or absent. In classic VHL disease, patients are germline heterozygous for mutations in VHL, and the present results suggest that a single wild-type allele for VHL is sufficient to maintain normal cardiopulmonary function. The HIF-2 alpha gain-of-function phenotype may be more limited than the Chuvash phenotype either because HIF-1 alpha is not elevated in the former condition, or because other HIF-independent functions of VHL are perturbed in Chuvash polycythemia.-Formenti, F., Beer, P. A., Croft, Q. P. P., Dorrington, K. L., Gale, D. P., Lappin, T. R. J., Lucas, G. S., Maher, E. R., Maxwell, P. H., McMullin, M. F., O'Connor, D. F., Percy, M. J., Pugh, C. W., Ratcliffe, P. J., Smith, T. G., Talbot, N. P., Robbins, P. A. Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation. FASEB J. 25, 2001-2011 (2011). www.fasebj.org

Systemic psychotherapy as an intervention for post-traumatic stress responses: an introduction, theoretical rationale and overview of developments in an emerging field of interest

The purpose of this article is to critically examine the literature to provide a rationale for including systemic family therapy (SFT) in the psycho-social treatment of people suffering the impact of post-traumatic stress (PTS). Attention is drawn to the relatively underdeveloped academic literature on PTS and the family. The impact of PTS is conceptualized within a psycho-social framework and the current evidence base for psycho-social interventions for PTS responses is described, highlighting the opportunity and need to undergird this area of daily practice. The impact of PTS on the family at multiple levels is identified, emphasizing its recursive nature. The case for SFT is articulated and a range of models of family intervention for PTS briefly reviewed, concluding with an emphasis on Walsh's key processes in family resilience as a framework for practice.

MicroRNA-155 Promotes Resolution of Hypoxia-Inducible Factor 1{alpha} Activity

The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1a (but not HIF-2a) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxia-inducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1a mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1a in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1a mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1a stabilization and activity. Based on these data and a mathematical model of HIF-1a suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1a activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1a-dependent transcription.

Induction of endothelial PAS domain protein-1 by hypoxia: Characterization and comparison with hypoxia-inducible factor-1 alpha

Hypoxia results in adaptive changes in the transcription of a range of genes including erythropoietin. An important mediator is hypoxia-inducible factor-1 (HIF-1), a DNA binding complex shown to contain at least two basic helix-loop-helix PAS-domain (bHLH-PAS) proteins, HIF-1 alpha and aryl hydrocarbon nuclear receptor translocator (ARNT), In response to hypoxia, HIF-1 alpha is activated and accumulates rapidly in the cell. Endothelial PAS domain protein 1 (EPAS-1) is a recently identified bHLH-PAS protein with 48% identity to HIF-1 alpha, raising the question of its role in responses to hypoxia. We developed specific antibodies and studied expression and regulation of EPAS-1 mRNA and protein across a range of human cell lines. EPAS-1 was widely expressed, and strongly induced by hypoxia at the level of protein but not mRNA. Comparison of the effect of a range of activating and inhibitory stimuli showed striking similarities in the EPAS-1 and HIF-1 alpha responses. Although major differences were observed in the abundance of EPAS-1 and HIF-1 alpha in different cell types, differences in the inducible response were subtle with EPAS-1 protein being slightly more evident in normoxic and mildly hypoxic cells. Functional studies in a mutant cell line (Ka13) expressing neither HIF-1 alpha nor EPAS-1 confirmed that both proteins interact with hypoxically responsive targets, but suggest target specificity with greater EPAS-1 transactivation (relative to HIF-1 alpha transactivation) of the VEGF promoter than the LDH-A promoter. (C) 1998 by The American Society of Hematology.

Evaluation of hepatic changes and local and systemic immune responses in goats immunized with recombinant Peroxiredoxin (Prx) and challenged with Fasciola hepatica

Protection against Fasciola hepatica in goats immunized with Peroxiredoxin (Prx) was assessed. The experimental trial consisted of three groups of seven animals: group 1 were unimmunized and uninfected, group 2 were immunized with adjuvant only and group 3 were immunized with recombinant Prx in adjuvant (immunized and infected). Immunization with Prx in Quil A adjuvant, group 3, induced a reduction in fluke burden of 33.04% when compared to adjuvant control, group 2, although this difference was not significant. The hepatic gross and microscopical morphometric study revealed lower damage in the Prx-immunized compared to group 2 (p

Sequence analysis of the 3' hypoxia-responsive element of the human erythropoietin gene in patients with erythrocytosis

Erythrocytosis arises from a variety of pathogenic mechanisms. We sequenced a 256-bp region 3' to the erythropoietin (Epo) gene which included a 24- to 50-bp minimal hypoxia-responsive element spanning HIF-1- and HNF-4-binding sites in 12 patients with erythrocytosis and 4 normal subjects. Four polymorphisms were found, none of which affected the HIF-1-binding site, although one polymorphism was present in the HNF-4 consensus region. The data indicate that none of these polymorphisms cause erythrocytosis.