Tribology of enzymatically degraded cartilage mimicking early osteoarthritis

Healthy cartilage is a water-filled super lubricious tissue. Collagen type II provides it structural stability, and proteoglycans absorb water to keep the cartilage in a swollen condition, providing it the ability to creep and provide weeping lubrication. Osteoarthritis (OA) is a degenerative and debilitating disorder of diarthrodial joints, where articular cartilage damage originates from enzymatic degradation and mechanical damage (wear). The objective of this research is to observe the level of cartilage damage present in knee arthroplasty patients and to understand the friction and creep behavior of enzymatically degraded bovine cartilage in vitro. Lateral (Lat) and medial (Med) condylar cartilages from OA patients undergoing total knee arthroplasty showed signs of enzymatic degradation and mechanical damage. Bovine cartilages were exposed to collagenase III and chondroitinase ABC to degrade collagen and proteoglycans, respectively. The loss of proteoglycans or collagen network and morphological changes were observed through histology and the atomic force microscope (AFM), respectively. A significant effect on creep due to enzymatic treatment was not observed. But the enzymatic treatment was found to significantly decrease the coefficient of friction (COF) at 4 N, while higher COF was shown from chondroitinase ABC degraded cartilage at 40 N. Collagenase III treatment leads to the release of intact proteoglycans at the sliding interface, while chondroitinase ABC treatment leads to the loss of chondroitin sulfate (CS) from the proteoglycans. Chondroitinase ABC-digested bovine cartilage mimicked patient samples the best because of the similar distributions of proteoglycans, collagen network, and friction behavior.[Figure not available: see fulltext.].</p

Time spent in primary care for hip osteoarthritis patients once the diagnosis is set: a prospective observational study

Background: Previous research on time to referral to orthopaedic surgery has predominantly used hip complaints as starting point instead of the moment the diagnosis of osteoarthritis (OA) of the hip is established, therefore little is known about the length of time a patient diagnosed with hip OA stays under the care of a general practitioner (GP). No knowledge on factors of influence on this time period is available either. Aim of this study was thus to determine the time an incident hip OA patient stays in the care of a GP until referral to an orthopaedic department. Influencing factors were also analyzed. Methods: A prospective observational study was conducted based on data over a 10-year period from a general practice-based registration network (17 GPs, > 30,000 patients registered yearly). Patients with the diagnosis of hip OA were included. A survival analysis was used to determine time until referral to an orthopaedic department, and to determine factors of influence on this time. Results: Of 391 patients diagnosed with hip OA, 121 (31%) were referred; average survival time until referral was 82.0 months (95% CI 76.6-87.5). Less contact with the GP for hip complaints before the diagnosis of hip OA was established resulted in a decreased time to referral. Conclusions: The results of this study show that patients with hip OA were under the care of a general practitioner, and thus in primary care, for a considerable amount of time once the diagnosis of hip OA was established

Anterior shear strength of the porcine lumbar spine after laminectomy and partial facetectomy

Degenerative lumbar spinal stenosis is the most common reason for lumbar surgery in patients in the age of 65 years and older. The standard surgical management is decompression of the spinal canal by laminectomy and partial facetectomy. The effect of this procedure on the shear strength of the spine has not yet been investigated in vitro. In the present study we determined the ultimate shear force to failure, the displacement and the shear stiffness after performing a laminectomy and a partial facetectomy. Eight lumbar spines of domestic pigs (7 months old) were sectioned to obtain eight L2–L3 and eight L4–L5 motion segments. All segments were loaded with a compression force of 1,600 N. In half of the 16 motion segments a laminectomy and a 50% partial facetectomy were applied. The median ultimate shear force to failure with laminectomy and partial facetectomy was 1,645 N (range 1,066–1,985) which was significantly smaller (p = 0.012) than the ultimate shear force to failure of the control segments (median 2,113, range 1,338–2,659). The median shear stiffness was 197.4 N/mm (range 119.2–216.7) with laminectomy and partial facetectomy which was significantly (p = 0.036) smaller than the stiffness of the control specimens (median 216.5, 188.1–250.2). It was concluded that laminectomy and partial facetectomy resulted in 22% reduction in ultimate shear force to failure and 9% reduction in shear stiffness. Although relatively small, these effects may explain why patients have an increased risk of sustaining shear force related vertebral fractures after spinal decompression surgery

In vivo quantification of photosensitizer fluorescence in the skin-fold observation chamber using dual-wavelength excitation and NIR imaging

A major challenge in biomedical optics is the accurate quantification of in vivo fluorescence images. Fluorescence imaging is often used to determine the pharmacokinetics of photosensitizers used for photodynamic therapy. Often, however, this type of imaging does not take into account differences in and changes to tissue volume and optical properties of the tissue under interrogation. To address this problem, a ratiometric quantification method was developed and applied to monitor photosensitizer meso-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method employs a combination of dual-wavelength excitation and dualwavelength detection. Excitation and detection wavelengths were selected in the NIR region. One excitation wavelength was chosen to be at the Q band of mTHPC, whereas the second excitation wavelength was close to its absorption minimum. Two fluorescence emission bands were used; one at the secondary fluorescence maximum of mTHPC centered on 720 nm, and one in a region of tissue autofluorescence. The first excitation wavelength was used to excite the mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be subtracted. Subsequently, the autofluorescence-corrected mTHPC image was divided by the autofluorescence signal to correct for variations in tissue optical properties. This correction algorithm in principle results in a linear relation between the corrected fluorescence and photosensitizer concentration. The limitations of the presented method and comparison with previously published and validated techniques are discussed

Engaging new migrants in infectious disease screening: a qualitative semi-structured interview study of UK migrant community health-care leads.

Migration to Europe - and in particular the UK - has risen dramatically in the past decades, with implications for public health services. Migrants have increased vulnerability to infectious diseases (70% of TB cases and 60% HIV cases are in migrants) and face multiple barriers to healthcare. There is currently considerable debate as to the optimum approach to infectious disease screening in this often hard-to-reach group, and an urgent need for innovative approaches. Little research has focused on the specific experience of new migrants, nor sought their views on ways forward. We undertook a qualitative semi-structured interview study of migrant community health-care leads representing dominant new migrant groups in London, UK, to explore their views around barriers to screening, acceptability of screening, and innovative approaches to screening for four key diseases (HIV, TB, hepatitis B, and hepatitis C). Participants unanimously agreed that current screening models are not perceived to be widely accessible to new migrant communities. Dominant barriers that discourage uptake of screening include disease-related stigma present in their own communities and services being perceived as non-migrant friendly. New migrants are likely to be disproportionately affected by these barriers, with implications for health status. Screening is certainly acceptable to new migrants, however, services need to be developed to become more community-based, proactive, and to work more closely with community organisations; findings that mirror the views of migrants and health-care providers in Europe and internationally. Awareness raising about the benefits of screening within new migrant communities is critical. One innovative approach proposed by participants is a community-based package of health screening combining all key diseases into one general health check-up, to lessen the associated stigma. Further research is needed to develop evidence-based community-focused screening models - drawing on models of best practice from other countries receiving high numbers of migrants

Defining the Boundaries of Normal Thrombin Generation: Investigations into Hemostasis

In terms of its soluble precursors, the coagulation proteome varies quantitatively among apparently healthy individuals. The significance of this variability remains obscure, in part because it is the backdrop against which the hemostatic consequences of more dramatic composition differences are studied. In this study we have defined the consequences of normal range variation of components of the coagulation proteome by using a mechanism-based computational approach that translates coagulation factor concentration data into a representation of an individual's thrombin generation potential. A novel graphical method is used to integrate standard measures that characterize thrombin generation in both empirical and computational models (e.g max rate, max level, total thrombin, time to 2 nM thrombin (“clot time”)) to visualize how normal range variation in coagulation factors results in unique thrombin generation phenotypes. Unique ensembles of the 8 coagulation factors encompassing the limits of normal range variation were used as initial conditions for the computational modeling, each ensemble representing “an individual” in a theoretical healthy population. These “individuals” with unremarkable proteome composition was then compared to actual normal and “abnormal” individuals, i.e. factor ensembles measured in apparently healthy individuals, actual coagulopathic individuals or artificially constructed factor ensembles representing individuals with specific factor deficiencies. A sensitivity analysis was performed to rank either individual factors or all possible pairs of factors in terms of their contribution to the overall distribution of thrombin generation phenotypes. Key findings of these analyses include: normal range variation of coagulation factors yields thrombin generation phenotypes indistinguishable from individuals with some, but not all, coagulopathies examined; coordinate variation of certain pairs of factors within their normal ranges disproportionately results in extreme thrombin generation phenotypes, implying that measurement of a smaller set of factors may be sufficient to identify individuals with aberrant thrombin generation potential despite normal coagulation proteome composition

Age-related changes in neural functional connectivity and its behavioral relevance

<p>Abstract</p> <p>Background</p> <p>Resting-state recordings are characterized by widely distributed networks of coherent brain activations. Disturbances of the default network - a set of regions that are deactivated by cognitive tasks and activated during passive states - have been detected in age-related disorders such as Alzheimer's or Parkinson's disease but alterations in the course of healthy aging still need to be explored.</p> <p>Results</p> <p>Using magnetoencephalography (MEG), the present study investigated how age-related functional resting-state brain connectivity links to cognitive performance in healthy aging in fifty-three participants ranging in age from 18 to 89 years. A beamforming technique was used to reconstruct the brain activity in source space and the interregional coupling was investigated using partial directed coherence (PDC). We found significant age-related alterations of functional resting-state connectivity. These are mainly characterized by reduced information input into the posterior cingulum/precuneus region together with an enhanced information flow to the medial temporal lobe. Furthermore, higher inflow in the medial temporal lobe subsystem was associated with weaker cognitive performance whereas stronger inflow in the posterior cluster was related to better cognitive performance.</p> <p>Conclusion</p> <p>This is the first study to show age-related alterations in subsystems of the resting state network that are furthermore associated with cognitive performance.</p