Expression of pannexin isoforms in the systemic murine arterial network

Aims: Pannexins (Panx) form ATP release channels and it has been proposed that they play an important role in the regulation of vascular tone. However, distribution of Panx across the arterial vasculature is not documented. Methods: We tested antibodies against Panx1, Panx2 and Panx3 on human embryonic kidney cells (which do not endogenously express Panx proteins) transfected with plasmids encoding each Panx isoform and Panx1(-/-) mice. Each of the Panx antibodies was found to be specific and was tested on isolated arteries using immunocytochemistry. Results: We demonstrated that Panx1 is the primary isoform detected in the arterial network. In large arteries, Panx1 is primarily in endothelial cells, whereas in small arteries and arterioles it localizes primarily to the smooth muscle cells. Panx1 was the predominant isoform expressed in coronary arteries, except in arteries less than 100 μm where Panx3 became detectable. Only Panx3 was expressed in the juxtaglomerular apparatus and cortical arterioles. The pulmonary artery and alveoli had expression of all 3 Panx isoforms. No Panx isoforms were detected at the myoendothelial junctions. Conclusion: We conclude that the specific localized expression of Panx channels throughout the vasculature points towards an important role for these channels in regulating the release of ATP throughout the arterial network.     

Erosive pustular dermatosis of the scalp in an adolescent with near‐total hair regrowth: Case report and review of the literature

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon chronic inflammatory response to scalp trauma that usually resolves with cicatricial alopecia. It most commonly affects elderly patients with a history of actinic damage. Herein, we describe a 16‐year‐old girl with acrofacial dysostosis type 1 presenting after surgery with crusting purulent scalp lesions, whose clinical presentation and histopathologic findings were consistent with EPDS. A review of the literature on EPDS in children is also detailed.     

Transapical aortic valve implantation – a rescue procedure for patients with aortic stenosis and “porcelain aorta”

Surgical aortic valve replacement (AVR) still remains the treatment of choice in symptomatic significant aortic stenosis (AS). Due to technical problems, extensive calcification of the ascending aorta (“porcelain aorta”) is an additional risk factor for surgery and transapical aortic valve implantation (TAAVI) is likely to be the only rescue procedure for this group of patients. We describe the case of an 81-year-old woman with severe AS and “porcelain aorta”, in whom the only available life-saving intervention was TAAVI.     

Trypanosoma cruzi infection induces a massive extrafollicular and follicular splenic B-cell response which is a high source of non-parasite-specific antibodies

Acute infection with Trypanosoma cruzi, the aetiological agent of Chagas’ disease, results in parasitaemia and polyclonal lymphocyte activation. It has been reported that polyclonal B‐cell activation is associated with hypergammaglobulinaemia and delayed parasite‐specific antibody response. In the present study we analysed the development of a B‐cell response within the different microenvironments of the spleen during acute T. cruzi infection. We observed massive germinal centre (GC) and extrafollicular (EF) responses at the peak of infection. However, the EF foci were evident since day 3 post‐infection (p.i.), and, early in the infection, they mainly provided IgM. The EF foci response reached its peak at 11 days p.i. and extended from the red pulp into the periarteriolar lymphatic sheath. The GCs were detected from day 8 p.i. At the peak of parasitaemia, CD138⁺ B220⁺ plasma cells in EF foci, red pulp and T‐cell zone expressed IgM and all the IgG isotypes. Instead of the substantial B‐cell response, most of the antibodies produced by splenic cells did not target the parasite, and parasite‐specific IgG isotypes could be detected in sera only after 18 days p.i. We also observed that the bone marrow of infected mice presented a strong reduction in CD138⁺ B220⁺ cells compared with that of normal mice. Hence, in acute infection with T. cruzi, the spleen appears to be the most important lymphoid organ that lodges plasma cells and the main producer of antibodies. The development of a B‐cell response during T. cruzi infection shows features that are particular to T. cruzi and other protozoan infection but different to other infections or immunization with model antigens.     

Investigation of scattered radiation in 3D whole-body positron emission tomography using Monte Carlo simulations

The correction of scattered radiation is one of the most challenging tasks in 3D positron emission tomography (PET) and knowledge about the amount of scatter and its distribution is a prerequisite for performing an accurate correction. One concern in 3D PET in contrast to 2D PET is the scatter contribution from activity outside the field-of-view (FOV) and multiple scatter. Using Monte Carlo simulations, we examined the scatter distribution for various phantoms. The simulations were performed for a whole-body PET system (ECAT EXACT HR+, Siemens/CTI) with an axial FOV of 15.5 cm and a ring diameter of 82.7 cm. With (without) interplane septa, up to one (two) out of three detected events are scattered (for a centred point source in a water-filled cylinder that nearly fills out the patient port), whereby the relative scatter fraction varies significantly with the axial position. Our results show that for an accurate scatter correction, activity as well as scattering media outside the FOV have to be taken into account. Furthermore it could be shown that there is a considerable amount of multiple scatter which has a different spatial distribution from single scatter. This means that multiple scatter cannot be corrected by simply rescaling the single scatter component.     

A systematic review of randomised controlled trials of interventions reporting outcomes for relatives of people with psychosis

Relatives play a key role in supporting people with psychosis at all stages of recovery, but this can be associated with high levels of distress. Family interventions, with an international evidence base, improve outcomes for service users but little is known about their impact on relatives' outcomes. This review of published evaluations aimed to assess whether family interventions are effective in improving outcomes for relatives of people with psychosis, to identify the key components of effective intervention packages, and to identify methodological limitations to be addressed in future research. Fifty studies were identified which evaluated an intervention to support relatives against a control group, and in which outcomes for the relatives were reported. Thirty (60%) studies showed a statistically significant positive impact of the intervention on at least one relatives' outcome category. Eleven key intervention components were identified across all 50 studies, but there was no evidence that the presence or absence of any of these key components reliably distinguished effective from ineffective interventions. Methodological quality of studies was generally poor with only 11 studies rated as adequate using the Clinical Trial Assessment Measure (CTAM). Recommendations to improve future research include larger samples; better defined interventions and controls; true randomisation and blind assessors; clearly specified primary outcomes; pre-published analysis plans that account appropriately for missing data and clustering of data; a consensus on the most relevant outcomes to assess and valid and reliable measures to do so. Alternative research designs need to be considered to evaluate more recent approaches which focus on family support, personalised to meet individual need, and offered as an integral part of complex clinical services.     

DOES VISUAL SUBORDINATE-LEVEL CATEGORISATION ENGAGE THE FUNCTIONALLY DEFINED FUSIFORM FACE AREA?

Functional magnetic resonance imaging was used to compare brain activation associated with basic-level (e.g. bird) and subordinate-level (e.g. eagle) processing for both visual and semantic judgements. We localised the putative face area for 11 subjects, who also performed visual matching judgements for pictures and aurally presented words. The middle fusiform and occipital gyri were recruited for subordinate minus basic visual judgements, reflecting additional perceptual processing. When the face area was localised individually for each subject, analyses in the middle fusiform gyri revealed that subordinate-level processing activated the individuals face area. We propose that what is unique about the way faces engage this region is the focal spatial distribution of the activation rather than the recruitment of the face per se. Eight subjects also performed semantic judgements on aurally presented basic- and subordinate-level words. The parahippocampal gyri were more activated for subordinate-level than basic-level semantic judgements. Finally, the left posterior inferior temporal gyrus was activated for subordinate-level judgements, both visual and semantic, as well as during passive viewing of faces.     

HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells

HIV infection is characterized by a brisk immune activation that plays an important role in the CD4 depletion and immune dysfunction of patients with AIDS. The mechanism underlying this activation is poorly understood. In the current study, we tested the hypothesis that this activation is the net product of two distinct pathways: the inflammatory response to HIV infection and the homeostatic response to CD4 T cell depletion. Using ex vivo BrdU incorporation of PBMCs from 284 patients with different stages of HIV infection, we found that CD4 proliferation was better predicted by the combination of CD4 depletion and HIV viral load (R² = 0.375, P < 0.001) than by either parameter alone (CD4 T cell counts, R² = 0.202, P < 0.001; HIV viremia, R² = 0.302, P < 0.001). Interestingly, CD8 T cell proliferation could be predicted by HIV RNA levels alone (R² = 0.334, P < 0.001) and this predictive value increased only slightly (R² = 0.346, P < 0.001) when CD4 T cell depletion was taken into account. Consistent with the hypothesis that CD4 T cell proliferation is driven by IL-7 as a homeostatic response to CD4 T cell depletion, levels of phosphorylated STAT-5 were found to be elevated in naive subsets of CD4 and CD8 T cells from patients with HIV infection and in the central memory subset of CD4 T cells. Taken together these data demonstrate that at least two different pathways lead to immune activation of T cells in patients with HIV infection and these pathways differentially influence CD4 and CD8 T cell subsets.