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In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage. Finite element models were constructed from microCT scans of trabecular bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected the elastic modulus at the apparent level. The volume fraction of trabecular bone was higher in the medial compartment compared to the lateral compartment of tibiae with cartilage damage (but not the controls), suggesting that mechanical properties were preserved in part at the apparent level by an increase in the bone volume fraction. It seems likely that the normal equilibrium between cartilage properties, bone tissue properties and bone volume fraction is disrupted early in the development of osteoarthritis. © 2001 Orthopaedic Research Society. Punlished by Elsevier Science Ltd. All rights reserved.

Cemcalsancer screening programmes using cytomorphologi-cal criteria could be more efficient if the screening included objective individual risk factors for women with normal cytol-ogy, such as a test for high-risk human papillomavirus (HPV). The value of a PCR-based test for high-risk HPV types was studied in a cohort of 1622 women presenting in a routine triannual population-based screening programme. Women were included in the study when they had no previous history of cervical dysplasia; and their initial Pap smear was read as normal (Pap I or 2). The mean age of the women was 42 years (range 34-54 years) and mean follow-up time was 40 months (range 5-73 months). Women were referred for colpoxopically directed biopsies if they had had 2 successive cervical smears read as Pap 3a (mild to moderate dyskaryosis) or one read as ?Pap 3b (severe dyskaryosis). Women with histologically confirmed cervical intraepithelial neoplasia grade 111 (CIN 111) were considered positive cases. All women were tested for 14 high-risk HPV genotypes. Of the 86 high-risk HPV-positive women, 6 developed CIN 111, whereas only I of the 1536 HPV-negative women did. The women with normal Pap smears containing high-risk HPV genotypes were I 16 times (95% CI, 13-990) more at risk of developing CIN 111, in contrast to women without high-risk HPV. These results support the view that the interval between successive smears in cervical-cancer screening can be increased considerably for women with cyto-morphologically normal and high-risk HPV-negative cervical smears as determined by PCR. c 1996 Wiley-Liss, Inc. Detection of cytomorphologically abnormal cells in smears of the uterine cervix is used in cervical-cancer screening programmes to identify women with cervical cancer and cervical intraepithelial neoplasia (CIN). However, cytomorpho-logical examination has major drawbacks (Koss, 1989). The percentage of false-negative cervical smears varies from 15 to SO%, while the number of false-positive smears is about 10% (Coppleson and Brown, 1974). This means that the sensitivity of cytology for cervical cancer and CIN is quite low (5 0 4 5 %) and the specificity is about 90%. The lack of sensitivity is compensated by repeating the procedure after a fairly short time interval, up to 3 years, depending on the result of the Pap-smear (IARC Working Group, 1986). There is strong epidemiological and molecular biological evidence that infection with high-risk human papillomaviruses (HPV) plays an important role in the development of cervical cancer (IARC Working Group, 1995). In addition, the relevant high-risk HPV types can now be detected in one PCR reaction (Wal-boomers et al., 1994). Thus, the question has been raised whether cervical-cancer screening may become more efficient when testing for high-risk HPV DNA is included in thc screening procedure (Meijer et al., 1992). In this study we evaluate whether the presence of high-risk HPV types in cytomorphologically normal (Pap 1 or 2) cervical smears is predictive for development of CIN 111 among women ...

Thinning of the subchondral bone plate was found as a common observation 4 weeks after OA had been induced in two strains of mice having either a high or low bone phenotype, but no relation was found with the amount of cartilage damage. In addition, this study shows that different strains of mice can react differently to instability-induced OA with respect to the spatial arrangement of cartilage damage and changes in subchondral trabecular structure.

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In 2017 the cervical cancer screening program in The Netherlands will be revised. Cervical smears will primarily be tested for the presence of high-risk human papillomavirus (hrHPV) instead of cytology, and vaginal self-sampling will be offered to non-responders. This includes a potential risk that part of the women who would otherwise opt for a cervical smear will wait for self-sampling. However, self-sampling for hrHPV in a responder population has never been studied yet. The aim of this study was to investigate the applicability and accuracy of self-sampling in detecting hrHPV in a screening responder population. A total of 2049 women, aged 30-60years, participating in the screening program in The Netherlands were included from April 2013 to May 2015. After they had their cervical smear taken, women self-collected a cervicovaginal sample with a brush-based device, the Evalyn Brush. Both the cervical smear and self-sample specimen were tested with the COBAS 4800 HPV platform. The hrHPV prevalence was 8.0% (95% CI 6.9-9.2) among the physician-taken samples, and 10.0% (95% CI 8.7-11.3) among the self-samples. There was 96.8% (95% CI 96.0-97.5) concordance of hrHPV prevalence between self-samples and physician-taken samples. Women in our study evaluated self-sampling as convenient (97.1%), user-friendly (98.5%), and 62.8% preferred self-sampling over a physician-taken sampling for the next screening round. In conclusion, self-sampling showed high concordance with physician-taken sampling for hrHPV detection in a responder screening population and highly acceptable to women. Implementation of HPV-self-sampling for the responder population as a primary screening tool may be considered.

BackgroundA large portion of tissues stored worldwide for diagnostic purposes is formalin-fixed and paraffin-embedded (FFPE). These FFPE-archived tissues are an extremely valuable source for retrospective (genetic) studies. These include mutation screening in cancer-critical genes as well as pathogen detection. In this study we evaluated the impact of several widely used DNA extraction methods on the quality of molecular diagnostics on FFPE tissues.FindingsWe compared 4 DNA extraction methods from 4 identically processed FFPE mammary-, prostate-, colon- and lung tissues with regard to PCR inhibition, real time SNP detection and amplifiable fragment size. The extraction methods, with and without proteinase K pre-treatment, tested were: 1) heat-treatment, 2) QIAamp DNA-blood-mini-kit, 3) EasyMAG NucliSens and 4) Gentra Capture-Column-kit.Amplifiable DNA fragment size was assessed by multiplexed 200-400-600 bp PCR and appeared highly influenced by the extraction method used. Proteinase K pre-treatment was a prerequisite for proper purification of DNA from FFPE. Extractions with QIAamp, EasyMAG and heat-treatment were found suitable for amplification of fragments up to 400 bp from all tissues, 600 bp amplification was marginally successful (best was QIAamp). QIAamp and EasyMAG extracts were found suitable for downstream real time SNP detection. Gentra extraction was unsuitable. Hands-on time was lowest for heat-treatment, followed by EasyMAG.ConclusionsWe conclude that the extraction method plays an important role with regard to performance in downstream molecular applications.

The skeleton is continuously being renewed in the bone remodeling process. This prevents accumulation of damage and adapts the architecture to external loads. A side effect is a gradual decrease of bone mass, strength, and stiffness with age. We investigated the effects of bone loss on the load distribution and mechanical properties of cancellous bone using three-dimensional (3D) computer models. Several bone loss scenarios were simulated. Bone matrix was removed at locations of high strain, of low strain, and random throughout the architecture. Furthermore, resorption cavities and thinning of trabeculae were simulated. Removal of 7% of the bone mass at highly strained locations had deleterious effects on the mechanical properties, while up to 50% of the bone volume could be removed at locations of low strain. Thus, if remodeling would be initiated only at highly strained locations, where repair is likely needed, cancellous bone would be continuously at risk of fracture. Thinning of trabeculae resulted in relatively small decreases in stiffness; the same bone loss caused by resorption cavities caused large decreases in stiffness and high strain peaks at the bottom of the cavities. This explains that a reduction in the number and size of resorption cavities in antiresorptive drug treatment can result in large reductions in fracture risk, with small increases in bone mass. Strains in trabeculae surrounding a cavity increased by up to 1000 microstrains, which could lead to bone apposition. These results give insight in the mechanical effects of bone remodeling and resorption at trabecular level.