3D profiling of mouse epiphyses across ages reveals new potential imaging biomarkers of early spontaneous osteoarthritis

Worldwide research groups and funding bodies have highlighted the need for imaging biomarkers to predict osteoarthritis (OA) progression and treatment effectiveness. Changes in trabecular architecture, which can be detected with non-destructive high-resolution CT imaging, may reveal OA progression before apparent articular surface damage. Here, we analysed the tibial epiphyses of STR/Ort (OA-prone) and CBA (healthy, parental control) mice at different ages to characterise the effects of mouse age and strain on multiple bony parameters. We isolated epiphyseal components using a semi-automated method, and measured the total epiphyseal volume; cortical bone, trabecular bone and marrow space volumes; mean trabecular and cortical bone thicknesses; trabecular volume relative to cortical volume; trabecular volume relative to epiphyseal interior (trabecular BV/TV); and the trabecular degree of anisotropy. Using two-way ANOVA (significance level ≤0.05), we confirmed that all of these parameters change significantly with age, and that the two strains were significantly different in cortical and trabecular bone volumes, and trabecular degree of anisotropy. STR/Ort mice had higher cortical and trabecular volumes and a lower degree of anisotropy. As the two mouse strains reflect markedly divergent OA predispositions, these parameters have potential as bioimaging markers to monitor OA susceptibility and progression. Additionally, significant age/strain interaction effects were identified for total epiphyseal volume, marrow space volume and trabecular BV/TV. These interactions confirm that the two mouse strains have different epiphyseal growth patterns throughout life, some of which emerge prior to OA onset. Our findings not only propose valuable imaging biomarkers of OA, but also provide insight into ageing 3D epiphyseal architecture bone profiles and skeletal biology underlying the onset and development of age-related OA in STR/Ort mice

The mu problem and sneutrino inflation

We consider sneutrino inflation and post-inflation cosmology in the singlet extension of the MSSM with approximate Peccei-Quinn(PQ) symmetry, assuming that supersymmetry breaking is mediated by gauge interaction. The PQ symmetry is broken by the intermediate-scale VEVs of two flaton fields, which are determined by the interplay between radiative flaton soft masses and higher order terms. Then, from the flaton VEVs, we obtain the correct mu term and the right-handed(RH) neutrino masses for see-saw mechanism. We show that the RH sneutrino with non-minimal gravity coupling drives inflation, thanks to the same flaton coupling giving rise to the RH neutrino mass. After inflation, extra vector-like states, that are responsible for the radiative breaking of the PQ symmetry, results in thermal inflation with the flaton field, solving the gravitino problem caused by high reheating temperature. Our model predicts the spectral index to be n_s\simeq 0.96 due to the additional efoldings from thermal inflation. We show that a right dark matter abundance comes from the gravitino of 100 keV mass and a successful baryogenesis is possible via Affleck-Dine leptogenesis.Comment: 27 pages, no figures, To appear in JHE

Parental stress before, during, and after pediatric stem cell transplantation: a review article

Goals of work: Pediatric stem cell transplantation (SCT) is a stressful treatment for children with relapsed or high-risk malignancies, immune deficiencies and certain blood diseases. Parents of children undergoing SCT can experience ongoing stress related to the SCT period. The aim of this article was to present a literature review of articles on parental distress and adaptation before, during, and after SCT and to identify risk and protective factors. Materials and methods: The review was conducted systematically by using PubMed, Web of Science, PsychInfo, and Picarta databases. Eighteen articles met our inclusion criteria: publishing date between January 1, 1990 and January 1, 2009; studies concerning parents of children undergoing SCT; studies examining the psychological adjustment and/or stress reactions of parents as primary outcomes and studies available in English. Main results: Highest levels of parental stress are reported in the period preceding SCT and during the acute phase. Stress levels decrease steadily after discharge in most parents. However, in a subgroup of parents, stress levels still remain elevated post-SCT. Parents most at risk in the longer term display highest levels of stress during the acute phase of the SCT. Conclusions: Psychosocial assessment before SCT, during the acute phase and in the longer term, is necessary to identify parents in need for support and follow-up care

Construct validation of the Health Utilities Index and the Child Health Questionnaire in children undergoing cancer chemotherapy

The objective of this study was to evaluate the construct validity of two questionnaire-based measures of health-related quality of life (HRQL) in children undergoing cancer chemotherapy: the Health Utilities Index (HUI) and the Child Health Questionnaire (CHQ). Subjects were children hospitalised for chemotherapy. To examine construct validity: (1) a priori expected relations between CHQ concepts and HUI attributes were examined; (2) HUI and CHQ summary scores were compared to visual analogue scale (VAS) scores. Ease of completion was rated using a 5-point categorical scale and completion time was recorded. A total of 36 subjects were included. The maximum score was seen in 15 (47%) of HUI3 assessments. As predicted, CHQ body pain was moderately correlated with HUI3 pain (r=0.51), CHQ physical functioning was moderately correlated with HUI2 mobility (r=0.58) and CHQ mental health was moderately correlated with HUI2 emotion (r=0.53). Only the CHQ psychosocial subscale (and not HUI) was correlated with VAS (r=0.44). The CHQ and the HUI were both easy to use. The HUI questionnaires required less time to complete (mean=3.1, s.d.=1 min) compared with CHQ (mean=13.1, s.d.=3.4 min, P<0.0001). In conclusion, HUI and CHQ demonstrated construct validity in children undergoing cancer chemotherapy. The Health Utilities Index is subject to a ceiling effect whereas CHQ requires more time to complete

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Profile of subjective quality of life and its correlates in a nation-wide sample of high school students in an Arab setting using the WHOQOL-Bref

<p>Abstract</p> <p>Background</p> <p>The upsurge of interest in the quality of life (QOL) of children is in line with the 1989 Convention on the Rights of the Child, which stressed the child's right to adequate circumstances for physical, mental, and social development. The study's objectives were to: (i) highlight how satisfied Kuwaiti high school students were with life circumstances as in the WHOQOL-Bref; (ii) assess the prevalence of at risk status for impaired QOL and establish the QOL domain normative values; and (iii) examine the relationship of QOL with personal, parental, and socio-environmental factors.</p> <p>Method</p> <p>A nation-wide sample of students in senior classes in government high schools (N = 4467, 48.6% boys; aged 14-23 years) completed questionnaires that included the WHOQOL-Bref.</p> <p>Results</p> <p>Using Cummins' norm of 70% - 80%, we found that, as a group, they barely achieved the well-being threshold score for physical health (70%), social relations (72.8%), environment (70.8%) and general facet (70.2%), but not for psychological health (61.9%). These scores were lower than those reported from other countries. Using the recommended cut-off of <1<it>SD </it>of population mean, the prevalence of at risk status for impaired QOL was 12.9% - 18.8% (population age-adjusted: 15.9% - 21.1%). In all domains, boys had significantly higher QOL than girls, mediated by anxiety/depression; while the younger ones had significantly higher QOL (<it>p </it>< 0.001), mediated by difficulty with studies and social relations. Although poorer QOL was significantly associated with parental divorce and father's low socio-economic status, the most important predictors of poorer QOL were perception of poor emotional relationship between the parents, poor self-esteem and difficulty with studies.</p> <p>Conclusion</p> <p>Poorer QOL seemed to reflect a circumstance of social disadvantage and poor psychosocial well-being in which girls fared worse than boys. The findings indicate that programs that address parental harmony and school programs that promote study-friendly atmospheres could help to improve psychosocial well-being. The application of QOL as a school population health measure may facilitate risk assessment and the tracking of health status.</p

Common and Distinct Genetic Properties of ESCRT-II Components in Drosophila

BACKGROUND: Genetic studies in yeast have identified class E vps genes that form the ESCRT complexes required for protein sorting at the early endosome. In Drosophila, mutations of the ESCRT-II component vps25 cause endosomal defects leading to accumulation of Notch protein and increased Notch pathway activity. These endosomal and signaling defects are thought to account for several phenotypes. Depending on the developmental context, two different types of overgrowth can be detected. Tissue predominantly mutant for vps25 displays neoplastic tumor characteristics. In contrast, vps25 mutant clones in a wild-type background trigger hyperplastic overgrowth in a non-autonomous manner. In addition, vps25 mutant clones also promote apoptotic resistance in a non-autonomous manner. PRINCIPAL FINDINGS: Here, we genetically characterize the remaining ESCRT-II components vps22 and vps36. Like vps25, mutants of vps22 and vps36 display endosomal defects, accumulate Notch protein and--when the tissue is predominantly mutant--show neoplastic tumor characteristics. However, despite these common phenotypes, they have distinct non-autonomous phenotypes. While vps22 mutations cause strong non-autonomous overgrowth, they do not affect apoptotic resistance. In contrast, vps36 mutations increase apoptotic resistance, but have little effect on non-autonomous proliferation. Further characterization reveals that although all ESCRT-II mutants accumulate Notch protein, only vps22 and vps25 mutations trigger Notch activity. CONCLUSIONS/SIGNIFICANCE: The ESCRT-II components vps22, vps25 and vps36 display common and distinct genetic properties. Our data redefine the role of Notch for hyperplastic and neoplastic overgrowth in these mutants. While Notch is required for hyperplastic growth, it appears to be dispensable for neoplastic transformation