Clinical factors associated with fatigue over time in paediatric oncology patients receiving chemotherapy

The purpose of this study was to investigate the relationships between clinical factors (including haemoglobin value, chemotherapeutic agents, and corticosteroid use) and changing patterns of fatigue before and for the next 10 days following the start of a new round of chemotherapy in children with cancer. A prospective longitudinal design was used to collect data from 48 paediatric oncology patients who were about to begin a new round of chemotherapy and their parents. Fatigue levels were assessed using multidomain questionnaires with three categories of patient self-report (including ‘General Fatigue', ‘Sleep/Rest Fatigue', and ‘Cognitive Fatigue') and four categories of parent proxy-report (including ‘Lack of Energy', ‘Unable to Function', ‘Altered Sleep', and ‘Altered Mood'). The findings suggest that fatigue from both patient self-report and parent proxy-report changed significantly over time. The major findings from this study are that patients have more problems with fatigue in the first few days after the start of a cycle of chemotherapy. Corticosteroid use and haemoglobin value were associated with significant increases in fatigue that were sustained for several days and reached the highest level of fatigue at day 5 for those receiving concurrent steroids. The association of chemotherapeutic agents with fatigue varied between patient self-report and parent report, but the type of chemotherapeutic agents used was not associated with most changes in fatigue

Accumulating Variation at Conserved Sites in Potyvirus Genomes Is Driven by Species Discovery and Affects Degenerate Primer Design

Unknown and foreign viruses can be detected using degenerate primers targeted at conserved sites in the known viral gene sequences. Conserved sites are found by comparing sequences and so the usefulness of a set of primers depends crucially on how well the known sequences represent the target group including unknown sequences. Methodology/Principal Findings: We developed a method for assessing the apparent stability of consensus sequences at sites over time using deposition dates from Genbank. We tested the method using 17 conserved sites in potyvirus genomes. The accumulation of knowledge of sequence variants over 20 years caused ‘consensus decay ’ of the sites. Rates of decay were rapid at all sites but varied widely and as a result, the ranking of the most conserved sites changed. The discovery and reporting of sequences from previously unknown and distinct species, rather than from strains of known species, dominated the decay, indicating it was largely a sampling effect related to the progressive discovery of species, and recent virus mutation was probably only a minor contributing factor. Conclusion/Significance: We showed that in the past, the sampling bias has misled the choice of the most conserved target sites for genus specific degenerate primers. The history of sequence discoveries indicates primer designs should be update

Measuring perceived benefit and disease-related burden in young cancer survivors: validation of the Benefit and Burden Scale for Children (BBSC) in the Netherlands

Item does not contain fulltextPURPOSE: Perceiving favourable changes from one's illness may go hand in hand with experiencing harmful psychosocial effects. Each of these constructs should be considered when examining children's levels of psychological adjustment following stressful life events. A paediatric instrument that accounts for both positive and negative impact of stressful events has not been investigated in The Netherlands before. The aim of the study was to investigate psychometric properties of the Dutch version of the Benefit and Burden Scale for Children (BBSC), a 20-item questionnaire that intends to measure potential benefit and burden of illness in children. METHODS: Dutch paediatric survivors of childhood cancer aged 8-18 (N = 77) completed the BBSC and other psychological questionnaires: Pediatric Quality of Life Inventory (health-related quality of life), State-Trait Anxiety Inventory for Children (anxiety), Children's Revised Impact of Event Scale (posttraumatic stress) and Strengths and Difficulties Questionnaire (behavioural functioning). Reliability and validity were evaluated. RESULTS: Internal consistency (Cronbach's alpha, benefit 0.84, burden 0.72), test-retest reliability (benefit r = 0.74, burden r = 0.78) and homogeneity (mean inter-item correlation, benefit r = 0.34, burden r = 0.22) were satisfactory. Burden was associated with HRQoL (-), anxiety (+), posttraumatic stress symptoms (+) and behavioural problems. Benefit did not correlate with the psychological outcomes. CONCLUSIONS: The Dutch version of the BBSC shows promising psychometric properties. Perceived benefit and disease-related burden are distinct constructs; both should be considered when examining children's psychological adjustment to potentially traumatic experiences. The BBSC may be useful as monitoring and screening instrument

Molecular, Biochemical and Genetic Characteristics of BSE in Canada

The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrPres). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrPres, including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6) and the other to L-type BSE (case 11). All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrPres from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrPres subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide

BSE can propagate in sheep co-infected or pre-infected with scrapie

To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with scrapie after being born into a scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or scrapie-like PrP Sc. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to scrapie had scrapie-like incubation periods and dominant scrapie PrP Sc in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental scrapie did not propagate BSE but VRQ/VRQ sheep with natural scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrP Sc strain in brain tissue. Indeed, for several animals, a dominant scrapie biochemical phenotype in brain did not preclude the presence of BSE prion

Income in Adult Survivors of Childhood Cancer.

INTRODUCTION: Little is known about the impact of childhood cancer on the personal income of survivors. We compared income between survivors and siblings, and determined factors associated with income. METHODS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to survivors, aged ≥18 years, registered in the Swiss Childhood Cancer Registry (SCCR), diagnosed at age 4'500 CHF), even after we adjusted for socio-demographic and educational factors (OR = 0.46, p<0.001). Older age, male sex, personal and parental education, and number of working hours were associated with high income. Survivors of leukemia (OR = 0.40, p<0.001), lymphoma (OR = 0.63, p = 0.040), CNS tumors (OR = 0.22, p<0.001), bone tumors (OR = 0.24, p = 0.003) had a lower income than siblings. Survivors who had cranial irradiation, had a lower income than survivors who had no cranial irradiation (OR = 0.48, p = 0.006). DISCUSSION: Even after adjusting for socio-demographic characteristics, education and working hours, survivors of various diagnostic groups have lower incomes than siblings. Further research needs to identify the underlying causes

Prion protein-specific antibodies that detect multiple TSE agents with high sensitivity

This paper describes the generation, characterisation and potential applications of a panel of novel anti-prion protein monoclonal antibodies (mAbs). The mAbs were generated by immunising PRNP null mice, using a variety of regimes, with a truncated form of recombinant ovine prion protein spanning residues 94–233. Epitopes of specific antibodies were mapped using solid-phase Pepscan analysis and clustered to four distinct regions within the PrP molecule. We have demonstrated the utility of these antibodies by use of Western blotting and immunohistochemistry in tissues from a range of different species affected by transmissible spongiform encephalopathy (TSE). In comparative tests against extensively-used and widely-published, commercially available antibodies, similar or improved results can be obtained using these new mAbs, specifically in terms of sensitivity of detection. Since many of these antibodies recognise native PrPC, they could also be applied to a broad range of immunoassays such as flow cytometry, DELFIA analysis or immunoprecipitation. We are using these reagents to increase our understanding of TSE pathogenesis and for use in potential diagnostic screening assays

Lysyl hydroxylase 3 localizes to epidermal basement membrane and Is reduced in patients with Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 protein. Exogenous type VII collagen did not alter LH3 expression in cultured RDEB keratinocytes and we show that RDEB patients receiving bone marrow transplantation who demonstrate significant increase in type VII collagen do not show increased levels of LH3 at the basement membrane. Our data report a direct link between LH3 and endogenous type VII collagen expression concluding that reduction of LH3 at the basement membrane in patients with RDEB will likely have significant implications for disease progression and therapeutic intervention