Fibroblast involvement in soft connective tissue calcification

Soft connective tissue calcification is not a passive process, but the consequence of metabolic changes of local mesenchymal cells that, depending on both genetic and environmental factors, alter the balance between pro- and anti-calcifying pathways. While the role of smooth muscle cells and pericytes in ectopic calcifications has been widely investigated, the involvement of fibroblasts is still elusive. Fibroblasts isolated from the dermis of pseudoxanthoma elasticum (PXE) patients and of patients exhibiting PXE-like clinical and histopathological findings offer an attractive model to investigate the mechanisms leading to the precipitation of mineral deposits within elastic fibers and to explore the influence of the genetic background and of the extracellular environment on fibroblast-associated calcifications, thus improving the knowledge on the role of mesenchymal cells on pathologic mineralizatio

Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region

Mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a heritable disease that affects elastic fibers. Thus far, >200 mutations have been characterized by various PCR-based techniques (primarily direct sequencing), identifying up to 90% of PXE-causing alleles. This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a high recombinational potential. To detect ABCC6 deletions/insertions, which can be missed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was applied in PXE patients with an incomplete genotype. MLPA was performed in 35 PXE patients with at least one unidentified mutant allele after exonic sequencing and exclusion of the recurrent exon 23-29 deletion. Six multi-exon deletions and four single-exon deletions were detected. Using MLPA in addition to sequencing, we expanded the ABCC6 mutation spectrum with 9 novel deletions and characterized 25% of unidentified disease alleles. Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions in the molecular diagnosis of PXE. Journal of Human Genetics (2010) 55, 112-117; doi: 10.1038/jhg.2009.132; published online 15 January 201

Prognosis and course of work-participation in patients with chronic non-specific low back pain: a 12-month follow-up cohort study

AbstractOBJECTIVE:To investigate the clinical course of, and prognostic factors for, work-participation in patients with chronic non-specific low back pain.METHODS:A total of 1,608 patients with chronic non-specific low back pain received a multidisciplinary therapy and were evaluated at baseline and 2-, 5- and 12-month follow-ups. Recovery was defined as absolute recovery if the patient worked 90% of his contract hours at follow-up. Potential factors were identified using multivariable logistic regression analysis.RESULTS:Patients reported a mean increase in work-participation from 38% at baseline to 82% after 12 months. Prognostic factors for ≥ 90% work-participation at 5 months were being married (odds ratio (OR) 1.72 (95% confidence interval (95% CI) 1.12-2.65)), male (OR 1.99 (95% CI 1.24-3.20)), a higher score on disability (OR 1.00 (95% CI 0.997-1.02)) and physical component scale (Short-Form 36 (SF-36)) (OR 1.05 (95% CI 1.02-1.07)), previous rehabilitation (OR 1.85 (95% CI 1.14-2.98)), not receiving sickness benefits (OR 0.52 (95% CI 0.24-1.10)) and more work-participation (OR 4.86 (95% CI 2.35-10.04)). More work-participation (OR 5.22 (95% CI 3.47-7.85)) and male sex (OR 1.79 (95% CI 1.25-2.55)) were also prognostic factors at 12-month follow-up.CONCLUSION:At 12 months 52% of patients reported ≥ 90% work-participation. The strongest prognostic factor was more work-participation at baseline for the recovery of chronic non-specific low back pai

Improving working conditions and job satisfaction in healthcare. A study concept design on a participatory organizational level intervention in psychosocial risks management

This paper contributes to the literature on organizational interventions on occupational health by presenting a concept study design to test the efficacy of a Participatory Organizational level Intervention to improve working conditions and job satisfaction in Healthcare. The Participatory Organizational-level Intervention is developed using the Italian methodology to assess and manage psychosocial risks tailored to Healthcare. We added an additional step; evaluation, aiming to examine how the intervention works, what worked for whom in which circumstances. This ongoing study is conducted in collaboration with two large Italian Hospitals (more than 7,000 employees). The study design comprises a quasi-experimental approach consisting of five phases and surveys distributed pre- and post-intervention aiming to capture improvements in working conditions and job satisfaction. Moreover, to evaluate the efficacy of the Intervention in terms of process and content, we use a realist evaluation to test Context-Mechanisms-Outcome (CMO) configurations. We collect contextual factors at baseline and during and post-intervention process data on the key principles of line manager support and employees participation. This study is expected to provide insights on methods and strategies to improve working conditions and employees’ job satisfaction and on national policies in the occupational health framework

Gender Equality in Diastasis Rectus Abdominis in Chronic Back Pain: A Model of M. Transversus Abdominis Motor Control Impairment

Introduction: Diastasis rectus abdominis (DRA) is defined as an increased distance between the left and right muscle of the m. rectus abdominis. Pregnancy-related factors are assumed to be dominant factors in the occurrence of DRA. However DRA is not only found in peri-partum women but also in men and nulliparous women with back or pelvic pain. This study provides an inventory of the incidence of DRA in subjects with chronic back and pelvic pain. If DRA is common in both men and women then other factors besides pregnancy, like impaired motor control, should be explored as cause for DRA.Material and Methods: This study was conducted with data from 849 back pain patients. Results from ultrasound assessment of the abdominal wall were combined with anamnestic data on age, gender, medical history and pregnancies (in women).Results: There was no difference in Inter Rectus Distance cranial of the umbilicus (IRD above umbilicus) between men and women. Almost half of all women and men (45% and 43%, respectively) exhibit an increased IRD above umbilicus. The incidence of an increased IRD above umbilicus is twice as high in women below 30 years, compared to men below 30 years old. This difference is not observed for men and women above 30 years old.Discussion: DRA occurs in women during pregnancy and increases with an increasing number of pregnancies. However, this condition does not affect significantly more women than men. Increased IRD above umbilicus already occurs in young men (mean age 30). Over 30 years of age, cranial of the umbilicus there is no difference in IRD between women and men. An alternative etiological mechanism is suggested

Hyaluronan uptake by adult human skin fibroblasts in vitro

Low and high molecular weight hyaluronan (HA) was added to adult human fibroblasts grown in monolayer to assess its influence on CD44 expression, its internalisation and effect on cell growth. CD44 expression on the surface of in vitro fibroblasts was not modified by different concentrations of FCS, whereas it was sensitive to cell cycle, being higher in the growing than in the resting phase. Independently from molecular weight, upon addition of exogenous HA (from 0.1 up to 1 mg/mL) to fibroblasts in the growing phase, a slight but constant decrease of the expression of CD44 on the surface of fibroblasts was observed; moreover, HA induced a rearrangement of CD44 into patches in close relationship with the terminal regions of stress fibers, which became thicker and more rigid after a few hours from the addition of HA to the medium. Fluorescent HA, added to the culture medium, rapidly attached to the plasma membrane and in less than two minutes was observed within cells, partly in association with its receptor CD44. By the contemporary use of neutral red, which accumulates into functional lysosomes, the great majority of internalised HA was found within lysosomes. HA receptor RHAMM-IHABP was rather homogeneously localised within the cytoplasm of normal growing fibroblasts. Upon addition of HA, the RHAMM-IHABP distribution became discontinuous around the nucleus. Addition of HA to fibroblasts induced a significant inhibition of cell growth, which was dependent on HA concentration and irrespective of HA molecular weight, at least in the ranges tested. Results show that extra-cellular HA is rapidly taken up by human dermal fibroblasts together with its CD44 receptor, and transported mostly to the lysosomes. Both low and high molecular weight HA induced down-regulation of cell proliferation, which would seem to be mediated by HA catabolism

Murine B Cell Development and Antibody Responses to Model Antigens Are Not Impaired in the Absence of the TNF Receptor GITR

The Glucocorticoid-Induced Tumor necrosis factor Receptor GITR, a member of the tumor necrosis factor receptor superfamily, has been shown to be important in modulating immune responses in the context of T cell immunity. B lymphocytes also express GITR, but a role of GITR in humoral immunity has not been fully explored. To address this question, we performed studies to determine the kinetics of GITR expression on naïve and stimulated B cells and the capacity of B cells to develop and mount antibody responses in GITR−/− mice. Results of our studies indicate that all mature B cells express GITR on the cell surface, albeit at different levels. Expression of GITR on naïve mature B cells is upregulated by BCR signaling, but is counteracted by helper T cell-related factors and other inflammatory signals in vitro. In line with these findings, expression of GITR on germinal center and memory B cells is lower than that on naïve B cells. However, the expression of GITR is strongly upregulated in plasma cells. Despite these differences in GITR expression, the absence of GITR has no effect on T cell-dependent and T cell-independent antibody responses to model antigens in GITR−/− mice, or on B cell activation and proliferation in vitro. GITR deficiency manifests only with a slight reduction of mature B cell numbers and increased turnover of naïve B cells, suggesting that GITR slightly contributes to mature B cell homeostasis. Overall, our data indicate that GITR does not play a significant role in B cell development and antibody responses to T-dependent and independent model antigens within the context of a GITR-deficient genetic background

Search for Θ+(1540)\Theta^+(1540) pentaquark in high statistics measurement of γp→Kˉ0K+n\gamma p \to \bar K^0 K^+ n at CLAS

The exclusive reaction $\gamma p \to \bar K^0 K^+ n$ was studied in the photon energy range between 1.6-3.8 GeV searching for evidence of the exotic baryon $\Theta^+(1540)\to nK^+$. The decay to $nK^+$ requires the assignment of strangeness $S=+1$ to any observed resonance. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility corresponding to an integrated luminosity of 70 $pb^{-1}$. No evidence for the $\Theta^+$ pentaquark was found. Upper limits were set on the production cross section as function of center-of-mass angle and $nK^+$ mass. The 95% CL upper limit on the total cross section for a narrow resonance at 1540 MeV was found to be 0.8 nb.Comment: Submitted to Physical Review Letter

Light Vector Mesons in the Nuclear Medium

The light vector mesons ($\rho$, $\omega$, and $\phi$) were produced in deuterium, carbon, titanium, and iron targets in a search for possible in-medium modifications to the properties of the $\rho$ meson at normal nuclear densities and zero temperature. The vector mesons were detected with the CEBAF Large Acceptance Spectrometer (CLAS) via their decays to $e^{+}e^{-}$. The rare leptonic decay was chosen to reduce final-state interactions. A combinatorial background was subtracted from the invariant mass spectra using a well-established event-mixing technique. The $\rho$ meson mass spectrum was extracted after the $\omega$ and $\phi$ signals were removed in a nearly model-independent way. Comparisons were made between the $\rho$ mass spectra from the heavy targets ($A > 2$) with the mass spectrum extracted from the deuterium target. With respect to the $\rho$-meson mass, we obtain a small shift compatible with zero. Also, we measure widths consistent with standard nuclear many-body effects such as collisional broadening and Fermi motion.Comment: 15 pages, 18 figures, 3 table

First measurement of coherent ϕ\phi-meson photoproduction on deuteron at low energies

The cross section and decay angular distributions for the coherent \phi meson photoproduction on the deuteron have been measured for the first time up to a squared four-momentum transfer t =(p_{\gamma}-p_{\phi})^2 =-2 GeV^2/c^2, using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The cross sections are compared with predictions from a re-scattering model. In a framework of vector meson dominance, the data are consistent with the total \phi-N cross section \sigma_{\phi N} at about 10 mb. If vector meson dominance is violated, a larger \sigma_{\phi N} is possible by introducing larger t-slope for the \phi N \to \phi N process than that for the \gamma N \to \phi N process. The decay angular distributions of the \phi are consistent with helicity conservation.Comment: 6 page