Objective The Hartley guinea pig develops articular cartilage degeneration similar to that seen in idiopathic human osteoarthritis. We investigated whether the application of pulsed low-intensity ultrasound (PLIUS) to the Hartley guinea pig joint would prevent or attenuate the progression of this degenerative process. Methods Treatment of male Hartley guinea pigs was initiated at the onset of degeneration (8 weeks of age) to assess the ability of PLIUS to prevent osteoarthritis, or at a later age (12 months) to assess the degree to which PLIUS acted to attenuate the progression of established disease. PLIUS (30 mW/cm2) was applied to stifle joints for 20 minutes per day over periods ranging from three to ten months, with contralateral limbs serving as controls. Joint cartilage histology was graded according to a modified Mankin scale to evaluate treatment effect. Immunohistochemical staining for IL-1 receptor antagonist (IL-1ra), MMP-3, MMP-13, and TGF-β1 was performed on the cartilage to evaluate patterns of expression of these proteins. Results PLIUS did not fully prevent cartilage degeneration in the prevention groups, but diminished the severity of the disease, with the treated joints showing markedly decreased surface irregularities and a much smaller degree of loss of matrix staining as compared to controls. PLIUS also attenuated disease progression in the groups with established disease, although to a somewhat lesser extent as compared to the prevention groups. Immunohistochemical staining demonstrated a markedly decreased degree of TGF-β1 production in the PLIUS-treated joints. This indicates less active endogenous repair, consistent with the marked reduction in cartilage degradation. Conclusions PLIUS exhibits the ability to attenuate the progression of cartilage degeneration in an animal model of idiopathic human OA. The effect was greater in the treatment of early, rather than established, degeneration.

Objectives: To explore the effects of low levels of first trimester Pregnancy Associated Plasma Protein-A (PAPP-A) on adverse pregnancy outcomes.Design: Single centre retrospective observational study. Setting: District general hospital.Population: Women with singleton pregnancies with low PAPP-A, attending Heatherwood and Wexham Park Hospital for first trimester combined screening for Down syndrome.Methods: Data was collected from Astraia Database and CMiS maternity system. Multiple linear regression models for birth weight and gestational age at delivery were developed after adjusting for confounding variables. Logistic regressions were dichotomised for preterm delivery into <34 weeks and ≥ 34 weeks, birth weight centiles, into <10 th centile and ≥10 th centile, and pre-eclampsia versus no pre-eclampsia. Main outcome measures:Preterm birth, small for gestational age (SGA) and pre-eclampsia.Results: PAPP-A levels of ≤0.4MoM is associated with SGA <10 th centile at p=0.04 with a positive predictive value (PPV) of 83.3% and negative predictive value (NPV) of 79.3%. Similarly, association with preterm birth <34 weeks is also significant at p=0.05 with PPV of 66% and NPV of 87.4%. A significant association with pre-eclampsia (p=0.6) could not be identified. In our study data of PAPP-A ≤0.4 MoM, for every 0.1MoM fall in PAPP-A, there was a reduction in birth weight by 78gm and an earlier birth by 5.3 days. Conclusion:There is an increased likelihood of preterm delivery and SGA with progressive reduction of PAPP-A levels below ≤0.4 MoM.