Inflammatory, abscess-forming foreign body reaction mimics a thrombus formation on an atrial septal defect closure device: A commented case report.

We are presenting a case of floating left and right atrial formations on an atrial septal defect occluder system (23mm StarFLEX)-Occluder) initially supposed to be thrombotic appositions in a 57-year-old man. The closure was performed on the background of left hemispheric stroke and atrial septal aneurysm (ASA) with patent foramen ovale (PFO). The suspect structures were detected in the 6-month follow-up by transesophageal echocardiography (TEE). The patient underwent a successful surgical explantation of the closure device and closure of the patent foramen ovale (PFO) using a pericardial patch. The pathological evaluation of the biatrial device associated appositions revealed hytrophic heart muscle tissue with perifocal scarring and purulent abscess-forming, granulating and foam-cell including inflammatory foreign body reaction instead of the expected thrombus formation.     

A PKR-like eukaryotic initiation factor 2alpha kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains

The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is induced as part of the IFN response in mammals and acts to shut down protein synthesis by the phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha). In fish, a PKR-like kinase activity has been detected, but the enzyme responsible has eluded characterization. Here, we describe a PKR-like kinase from zebrafish. Phylogenetic analysis shows that the C-terminal kinase domain is more closely related to the kinase domain of PKR than to any of the other three known eIF2alpha kinases. Surprisingly, instead of the two dsRNA binding domains found at the N terminus of PKR, there are two Zalpha domains. Zalpha domains specifically bind dsDNA and RNA in the left-handed Z conformation, often with high affinity. They have been found previously in two other IFN-inducible proteins, the dsRNA editing enzyme, ADAR1, and Z-DNA binding protein 1 (ZBP1), as well as in the poxvirus virulence factor, E3L. This previously undescribed kinase, designated PKZ (protein kinase containing Z-DNA binding domains), is transcribed constitutively at low levels and is highly induced after injection of poly(inosinic)-poly(cytidylic) acid, which simulates viral infection. Binding of Z-DNA by the Zalpha domain of PKZ was demonstrated by circular dichroism. PKZ inhibits translation in transfected cells; site-directed mutagenesis indicates that this inhibition depends on its catalytic activity. Identification of a gene combining Zalpha domains with a PKR-like kinase domain strengthens the hypothesis that the ability to bind left-handed nucleic acid plays a role in the host response to viruses.     

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology

Background/Aims: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure.Methods: The 5′-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12).Results: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25%, and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure.Conclusions: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.     

Individual, household and community factors associated with HIV test refusal in rural Malawi

Objective To investigate individual, household and community factors associated with HIV test refusal in a counselling and testing programme offered at population level in rural Malawi. Methods HIV counselling and testing was offered to individuals aged 18–59 at their homes. Individual variables were collected by interviews and physical examinations. Household variables were determined as part of a previous census. Multivariate models allowing for household and community clustering were used to assess associations between HIV test refusal and explanatory variables. Results Of 2303 eligible adults, 2129 were found and 1443 agreed to HIV testing. Test refusal was less likely by those who were never married [adjusted odds ratio (aOR) 0.50 for men (95% CI 0.32; 0.80) and 0.44 (0.21; 0.91) for women] and by farmers [aOR 0.70 (0.52; 0.96) for men and 0.59 (0.40; 0.87) for women]. A 10% increase in cluster refusal rates increased the odds of refusal by 1.48 (1.32; 1.66) in men and 1.68 (1.32; 2.12) in women. Women counsellors increased the odds of refusal by 1.39 (1.00; 1.92) in men. Predictors of HIV test refusal in women were refusal of the husband as head of household [aOR 15.08 (9.39; 24.21)] and living close to the main road [aOR 6.07 (1.76; 20.98)]. Common reasons for refusal were fear of testing positive, previous HIV test, knowledge of HIV serostatus and the need for more time to think. Conclusion Successful VCT strategies need to encourage couples counselling and should involve participation of men and communities.     

Retinoid X receptor beta polymorphisms do not explain functional differences in vitamins D and A response in Antineutrophil cytoplasmic antibody associated vasculitis patients

It has been suggested that the retinoid X receptor beta (RXRB) gene is a risk factor for Wegener's granulomatosis. We addressed if there is a functional difference in the response to retinoic acid (RA) and vitamin D in Antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis (AASV) patients and if this was associated with RXRB genotypes. TNFα and IL-10 production were measured in whole blood assay from AASV patients (n = 51) and healthy controls (HC, n = 67). One micromolar of 1,25-(OH)₂ D3, 9-cis RA (9c-RA) or all-trans RA (ATRA) was added to the assay. Genotyping was performed for exons 7 and 2 of the RXRB gene and for a microsatellite in vicinity of the RXRB gene. Lipopolysaccharide (LPS) mediated TNFα production and IL-10 were significantly lower in patients. Addition of 1,25-(OH)₂ D3, ATRA or 9c-RA, blunted TNFα production, more pronounced in patients. Although all three compounds inhibited IL-10 production significantly in HC, only 1,25-(OH)₂ D3 was found to be effective in patients. Allele distribution of the RXRB microsatellite differed significantly between patients and HC. This was not found for the SNP in exons 2 and 7. Genotype of the latter correlated with the ability of 1,25-(OH)₂ D3 and ATRA to inhibit IL-10 production. We provide immunological evidence for a functional difference in vitamins D and A responsiveness in AASV patients. Since the inhibition of TNFα was more effective in patients, vitamin D supplementation might be an additional therapeutical approach.     

High frequency of disease progression in pediatric spinal cord low-grade glioma (LGG): management strategies and results from the German LGG study group

BackgroundKnowledge on management of pediatric spinal cord low-grade glioma (LGG) is scarce.MethodsWe analyzed clinical datasets of 128 pediatric patients with spinal LGG followed within the prospective multicenter trials HIT-LGG 1996 (n = 36), SIOP-LGG 2004 (n = 56), and the subsequent LGG-Interim registry (n = 36).ResultsSpinal LGG, predominantly pilocytic astrocytomas (76%), harbored KIAA1549-BRAF fusion in 14/35 patients (40%) and FGFR1-TACC1 fusion in 3/26 patients (12%), as well as BRAFV600E mutation in 2/66 patients (3%). 10-year overall survival (OS) and event-free survival (EFS) was 93% ± 2% and 38% ± 5%, respectively. Disseminated disease (n = 16) was associated with inferior OS and EFS, while age ≥11 years and total resection were favorable factors for EFS. We observed 117 patients following total (n = 24) or subtotal/partial resection (n = 74), biopsy (n = 16), or radiologic diagnosis only (n = 3). Eleven patients were treated first with chemotherapy (n = 9) or irradiation (n = 2). Up to 20.8 years after diagnosis/initial intervention, 73/128 patients experienced one (n = 43) or up to six (n = 30) radiological/clinical disease progressions. Tumor resections were repeated in 36 patients (range, 2-6) and 47 patients required nonsurgical treatment (chemotherapy, n = 20; radiotherapy, n = 10; multiple treatment lines, n = 17). Long-term disease control for a median of 6.5 (range, 0.02-20) years was achieved in 73/77 patients following one (n = 57) or repeated (n = 16) resections, and in 35/47 patients after nonsurgical treatment.ConclusionsThe majority of patients experienced disease progression, even after years. Multiple interventions were required for more than a third, yet multimodal treatment enabled long-term disease control. Molecular testing may reveal therapeutic targets.     

Large-scale characterization of the microvascular geometry in development and disease by tissue clearing and quantitative ultramicroscopy

Three-dimensional assessment of optically cleared, entire organs and organisms has recently become possible by tissue clearing and selective plane illumination microscopy (“ultramicroscopy”). Resulting datasets can be highly complex, encompass over a thousand images with millions of objects and data of several gigabytes per acquisition. This constitutes a major challenge for quantitative analysis. We have developed post-processing tools to quantify millions of microvessels and their distribution in three-dimensional datasets from ultramicroscopy and demonstrate the capabilities of our pipeline within entire mouse brains and embryos. Using our developed acquisition, segmentation, and analysis platform, we quantify physiological vascular networks in development and the healthy brain. We compare various geometric vessel parameters (e.g. vessel density, radius, tortuosity) in the embryonic spinal cord and brain as well as in different brain regions (basal ganglia, corpus callosum, cortex). White matter tract structures (corpus callosum, spinal cord) showed lower microvascular branch densities and longer vessel branch length compared to grey matter (cortex, basal ganglia). Furthermore, we assess tumor neoangiogenesis in a mouse glioma model to compare tumor core and tumor border. The developed methodology allows rapid quantification of three-dimensional datasets by semi-automated segmentation of fluorescently labeled objects with conventional computer hardware. Our approach can aid preclinical investigations and paves the way towards “quantitative ultramicroscopy”.     

Is it feasible to assess self-reported quality of life in individuals who are deaf and have intellectual disabilities?

Purpose

There is consensus that Quality of Life (QOL) should be obtained through self-reports from people with intellectual Disability (ID). Thus far, there have been no attempts to collect self-reported QOL from people who are deaf and have ID.

Methods

Based on an established short measure for QOL (EUROHIS-QOL), an adapted easy-to-understand sign language interview was developed and applied in a population (n = 61) with severe-to-profound hearing loss and mild-to-profound ID. Self-reports were conducted at two time points (t₁ and t₂), 6 months apart. The Stark QOL, an established picture-based questionnaire, was also obtained at t₂ and three Proxy ratings of QOL (from caregivers) were conducted for each participant at t₁.

Results

Self-reported QOL was successfully administered at both time points for 44 individuals with mild and moderate ID (IQ reference age between 3.3 and 11.8 years).

The self-reports showed sufficient test–retest reliability and significant correlations with the Stark QOL. As anticipated, self-reported QOL was higher than proxy-reported QOL. Test–retest reliability and internal consistency were good for self-reported QOL.

Conclusion

Reliable and valid self-reports of QOL can be obtained from deaf adults with mild-moderate ID using standard inventories adapted to the linguistic and cognitive level of these individuals.