Dysregulated energy metabolism impairs chondrocyte function in osteoarthritis.

OBJECTIVES: Metabolic pathways are a series of chemical reactions by which cells take in nutrient substrates for energy and building blocks needed to maintain critical cellular processes. Details of chondrocyte metabolism and how it rewires during the progression of osteoarthritis (OA) are unknown. This research aims to identify what changes in the energy metabolic state occur in OA cartilage. METHODS: Patient matched OA and non-OA cartilage specimens were harvested from total knee replacement patients. Cartilage was first collected for metabolomics, proteomics, and transcriptomics analyses to study global alterations in OA metabolism. We then determined the metabolic routes by tracking [U-13C] isotope with liquid chromatography-mass spectrometry (LC-MS). We further evaluated cellular bioenergetic profiles by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) and investigated the effects of low-dose and short-term effects of 2-deoxyglucose (2DG) on chondrocytes. RESULTS: OA chondrocytes showed increased basal ECAR and more lactate production compared to non-OA chondrocytes. [U-13C] glucose labelling revealed that less glucose-derived carbon entered the tricarboxylic acid (TCA) cycle. On the other hand, mitochondrial respiratory rates were markedly decreased in the OA chondrocytes compared to non-OA chondrocytes. These changes were accompanied by decreased cellular ATP production, mitochondrial membrane potential and disrupted mitochondrial morphology. We further demonstrated in vitro that short-term inhibition of glycolysis suppressed matrix degeneration gene expression in chondrocytes and bovine cartilage explants cultured under inflammatory conditions. CONCLUSION: This study represents the first comprehensive comparative analysis of metabolism in OA chondrocytes and lays the groundwork for therapeutic targeting of metabolism in OA.

Attitudes towards risk-reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study.

OBJECTIVE: To determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. DESIGN: Multicentre, cohort, questionnaire study (IRSCTN:12310993). SETTING: United Kingdom (UK). POPULATION: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. METHODS: Participants completed a 39-item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. MAIN OUTCOMES: RRESDO acceptability, menopausal sequelae, satisfaction/regret. RESULTS: In all, 346 of 683 participants underwent risk-reducing salpingo-oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2-7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2-27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2-0.9, P = 0.025). CONCLUSION: Data show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness. TWEETABLE ABSTRACT: RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction.

Quinolone-induced Biceps Tendon Rupture.

Presentation A 76-year-old man presented with acute left upper limb pain and subsequent large ecchymosis. Diagnosis An ultrasound study was performed which showed partial left biceps tendon rupture. Treatment He was managed conservatively with Orthopaedic input. The patient was given analgesia and reassured. Discussion Tendon rupture is an unusual but serious complication of quinolone exposure. This case highlights that this should be included in the differential for acute limb pain in patients who have been prescribed these drugs.

Feasibility of Transthoracic Echocardiography Evaluation of Pulmonary Arteries Following Arterial Switch Operation.

Pulmonary artery (PA) stenosis is the most common late sequela following arterial switch for d-transposition of the great arteries. The purpose of this study was to assess the effectiveness of transthoracic echocardiography in evaluating the pulmonary arteries following repair. This was a retrospective, cross-sectional analysis of all echocardiograms performed on patients following arterial switch operation. A numerical scoring system was devised and used to quantify PA visualization based on 2D images, color mapping, and spectral Doppler. The study cohort included 150 patients. The ability to visualize at least one PA was poorer in patients who were older [> 10 years (47%) vs ≤ 10 years (89%) (p < 0.001)], and who had larger body surface area (BSA) (> 1.25 m2 (40%) vs ≤ 1.25 m2 (90%) (p < 0.001)]. Regardless of age, 2D visualization of the pulmonary arteries was poor for the entire cohort. Of those with at least one non-visualized PA, only 54% had alternative imaging performed or ordered within the 5 years at or prior to their last echocardiogram. In conclusion, PA visualization following arterial switch is worse in patients who are older and in those with larger BSA. In such patients, alternative forms of imaging are more likely to be necessary.

Preparing and sharing food: a quantitative analysis of a primary school-based food intervention.

Background: Primary schools are increasingly used as arenas for public health initiatives. The aim of this study was to assess a primary school-based food intervention. Methods: The intervention comprised timetabled kitchen classroom sessions (90 min, fortnightly). Pupils prepared and cooked food, which they then ate together. Children's relationship with food, including food enjoyment, experience and food neophobia, were addressed at the intervention school (baseline n = 154; follow-up n = 164) and at a matched control school (baseline n = 171; follow-up n = 174). Results: Pupils at the intervention school scored significantly higher (M = 3.90, SD = 1.81) for scores on Kitchen Equipment, compared to the control school (M = 3.06, SD = 2.12); and again scored significantly higher (M = 9.34, SD = 3.79) for the overall Cooking Experience Score compared to the control school (M = 7.98, SD = 4.57). Shifts accompanying the intervention in three outcome measures for pupils (taste description, liking for cooking and helping with cooking at home) were also revealed. No main intervention effect for food neophobia and fussiness was found; a close to significant time by intervention interaction (P = 0.053) was evident. Conclusions: The study indicates limited but encouraging changes, and contributes to the growing literature regarding school-based food initiatives.

Temporal change to self-rated health in the Swiss population from 1997 to 2012: the roles of age, gender, and education.

OBJECTIVES: Our study aimed to describe the temporal changes in self-rated health status (SRH) from 1997 to 2012 in adults aged 25 to 84 residing in Switzerland, with a view to identifying groups at risk for declining health. STUDY DESIGN: Secondary analysis of population-based cross-sectional health surveys. METHODS: Data were collected from the cross-sectional, population-based, five-year Swiss Health Survey, from 1997, 2002, 2007 and 2012. A total of 63,861 individuals' data were included. Multilevel mixed-effect logistic regression analysis was employed to estimate the probability of very good and good health within the framework of a hierarchical cross-classified age-period-cohort model (HAPC), adjusting for education level, gender, civil status, smoking status and body mass index. RESULTS: Individuals with higher education were substantially more likely than those with primary education to report good SRH (OR = 2.12; 95% CI = 1.93-2.33 for secondary education and OR = 3.79; 95% CI = 3.39-4.23 for tertiary education). The education effect depended on birth cohort and age: higher proportions of good SRH were reported by secondary (8%-17%) and tertiary (10%-22%) compared with primary educated individuals from the 1940 birth cohort onward; the proportion of secondary/tertiary (compared to primary) educated people reporting good SRH increased with age (by 10/11% at 45-50 years and 25/36% at 80-84 years). Gender health equality was achieved by the 1955 (primary educated) and 1960 (secondary educated) birth cohorts, while these women overtook men in reporting good SRH from the 1975 birth cohort onward. Tertiary educated younger women were significantly less likely to report good SRH than men but parity was achieved at around pension age. Similarly, gender inequality in those with primary and secondary education reduced in the younger ages to not be significant at around age 55, with women overtaking men from age 65. CONCLUSIONS: Younger birth cohorts with lower education levels appear most vulnerable in terms of their SRH. The education effect cumulatively increases when attaining incrementally higher education levels. While women report lower health than men, gender inequality in SRH has declined and even reversed over time and is substantially linked to differences in educational status. Swiss public health strategies should particularly target the younger adults with only primary school education of both genders; for women, to combat health burdens in their early life, and men, to mitigate issues in their later life.

Chondromodulin-1 ameliorates osteoarthritis progression by inhibiting HIF-2α activity.

OBJECTIVES: Hypoxia is known to stabilize hypoxia-inducible factor (HIF) and initiate angiogenic signaling cascade. However, cartilage living in hypoxia environment can maintain avascularity. It is well known that abrogation of avascularity is related to cartilage degradation in osteoarthritis (OA). The aims of present study were to investigate the role of chondromodulin-1 (ChM-1), an endogenously anti-angiogenic protein in cartilage, during chondrocyte maturation and OA progression, as well as to explore the molecular mechanisms underlying the function of ChM-1 with a focus on HIF-2α pathway. METHODS: Angiogenic-related markers were evaluated in OA cartilage and different stages of chondrocyte differentiation. Chondrocytes transfected with ChM-1 lentivirus or siRNA was treated with tumor necrosis factor (TNF-α) to investigate the role of ChM-1 in chondrocyte hypertrophic changes. In vivo study was conducted by using a surgical induced OA rat model with intra-articular injection of lentivirus ChM-1 (LV-ChM-1) or mock lentivirus (LV-GFP) control. Transcriptional activity of HIF-2α was determined by chromatin immunoprecipitation (ChIP) assay to unveil the mechanisms of ChM-1. RESULTS: Majority angiogenic factors increased in severe OA cartilage, while anti-angiogenic factors including ChM-1 decreased. ChM-1 expression was strongly related with chondrocyte differentiation and chondrogenesis in vitro. ChM-1 overexpression protected chondrocytes from TNF-α induced hypertrophy, and intra-articular injection of LV-ChM-1 delayed OA progression. ChM-1 delayed HIF-2α nuclear translocation at early time-points and decreased transcriptional activity of HIF-2α on collagen type Ð¥ α1 (COL10A1), vascular endothelial growth factor A (VEGFA) and matrix metallopeptidase-13 (MMP-13). CONCLUSIONS: ChM-1 maintains cartilage homeostasis by inhibiting HIF-2α induced catabolic activity and regulation of ChM-1 in cartilage may be a promising therapeutic strategy for OA.

'Between Combat boots and Birkenstocks'-Lessons from HIV/AIDS, SARS, H1N1 and Ebola.

OBJECTIVES: In late 2013, an Ebola outbreak quickly grew into an epidemic of extraordinary magnitude, killing more people than all previous Ebola outbreaks combined. Although the epidemic was unprecedented, the world had previously experienced several acute public health emergencies requiring global coordination. HIV/AIDS, SARS and H1N1 tested global response, and in each case coordination proved problematic, making the 2013-2015 Ebola epidemic no exception. The purpose of this project was to identify persistent vulnerabilities within global public health emergency response and to identify areas for future research and improvement. STUDY DESIGN: Non-systematic review and qualitative interview study. METHODS: Using PubMed and Google, a comprehensive search of articles connected to the HIV/AIDS, SARS, H1N1 and Ebola responses was conducted. Then, 21 key responders involved in those emergencies, primarily from the US Centers for Disease Control and Prevention, participated in in-depth interviews. The content analysis and in-depth interview data were analysed using MAXQDA analysis software. RESULTS: A number of issues emerged, including cultural and political clashes within relevant agencies and a lack of confidence in those agencies, policy barriers that hinder long-term international response, a shortage of personnel and resources, itemized funding streams that limit flexibility to direct resources, and challenges to deploying responders internationally. CONCLUSIONS: The data suggest that the world remains ill prepared to handle sustained responses and global pandemics. The study identified major vulnerabilities persistent within US-led global public health response and offers recommendations for further focused research to fully understand why these challenges persist.

High resolution anoscopy may be useful in achieving reductions in anal cancer local disease failure rates.

Anal cancer is uncommon, with an incidence rate of 0.5-1.0 per 100,000 of the population but incidence rates have been steadily increasing over the last 3 decades. Biological and epidemiological evidence have been mounting and demonstrate that anal cancer has many similarities to cervical cancer, especially in regard to its aetiology. High-resolution anoscopy (HRA) of the anal region ­ analogous to colposcopy of the cervix, is a technique that is not well-known in the medical and surgical fraternity. Evidence to support the use of HRA for detection and treatment in the surveillance of AIN exists and strongly suggests that it is beneficial, resulting in reduced rates of cancer progression. Pilot data from our study showed a local disease failure rate of 1.73 per 1000 patient-months compared with a published rate of 9.89 per 1000 patient-months. This demonstrates a 5.72-fold reduction in local disease failure rates of patients with T1-T3 tumours; the data therefore suggests that use of HRA for detection and treatment in surveillance of anal cancer patients will help prevent local regional relapse at the anal site. There is an urgent need for a large, randomised controlled clinical trial to definitively test this hypothesis.

A qualitative study of a food intervention in a primary school: Pupils as agents of change.

This study explored the impact of a school-based kitchen project at a large inner London school. Timetabled kitchen classroom sessions (90 min every fortnight) were held with all 7-9 year old pupils. Semi-structured focus group discussions (with 76 pupils, 16 parents) and interviews (with headteachers, catering managers and specialist staff) were conducted at the intervention school and a matched control school. Categories and concepts were derived using a grounded theory approach. Data analysis provided three main categories each with their related concepts: Pupil factors (enthusiasm and enjoyment of cooking, trying new foods, food knowledge and awareness, producing something tangible); School factors (learning and curriculum links, resource implications and external pressures) and Home factors (take home effects, confidence in cooking and self-esteem, parents' difficulties cooking at home with children). Children's engagement and the opportunity to cook supported increased food awareness, skills and food confidence. In the grounded theory that emerged, take home effects beyond the school gate dominate, as children act as agents of change and influence cooking and food choice at home. These short term outcomes have the potential to lead to longer term outcomes including changing eating behaviour and diet.

An evaluation of multimodal spinal cord monitoring in scoliosis surgery: a single centre experience of 354 operations.

PURPOSE: To evaluate the effectiveness of multimodal intraoperative neuromonitoring in the early detection of impending spinal cord injury during surgery for spinal deformity. METHOD: A retrospective review of prospectively collected data in 354 consecutive spinal deformity operations from June 2003 to October 2013. Patients were sub-grouped according to demographics, diagnosis and operative features. Post-operative neurological deficit was defined as either spinal cord, nerve root or transient deficit. RESULTS: Combined monitoring with SSEPs and MEPs was possible in 315 cases. The overall incidence of significant alerts was 7.1 % and overall permanent neurological deficit was 1.6 %. When results were collated, the overall combined sensitivity of multimodal monitoring was 100 % with a specificity of 99.3 %. CONCLUSIONS: Multimodal monitoring allows early detection of impending neurological deficit that is superior to a single monitoring modality. To achieve optimal use of monitoring, continuous communication between surgical, anaesthetic and neurophysiology teams are required. As a result of our experience we have incorporated in our consent procedure the discussion of monitoring and the possibility of needing to abandon the procedure, and completing in a staged fashion at a later date. We believe multimodal monitoring is the current gold standard for complex spinal deformity surgery.

Characterization of organic fluorophores for in vivo FRET studies based on electroporated molecules.

In vivo single-molecule fluorescence and Förster resonance energy transfer (FRET) techniques are excellent tools for studying spatial distribution, the nanoscale structure and conformational changes in living cells. We have recently introduced an electroporation-based method to internalize DNA and proteins labeled with organic fluorophores into living bacteria and established the ability for long-lived single-molecule fluorescence and FRET measurements. However, further developments, such as optimization of electroporation conditions, evaluation of organic fluorophore performance in vivo and quantitative single-cell FRET analysis, are needed to make the method more robust and general. Using singly-labeled DNA fragments, we optimized internalization efficiency and cell viability at six electroporation voltages, achieving >60% loading and viability similar to non-treated cells. We characterized the photostability and brightness of three donor fluorophores and four acceptor fluorophores in vivo; Cy3B, Atto647 and Atto647N performed best with photobleaching lifetimes of ∼20 s, 46 s and 92 s, respectively, and brightness values of ∼4000 photons per second under the same illumination conditions. We used three doubly-labeled DNA FRET standards (having in vitro FRET efficiencies of ∼17%, ∼42%, and ∼88%) and an alternating-laser excitation scheme to measure apparent FRET efficiencies at the single-cell level. We showed that we could differentiate DNA FRET standards at the single-cell level. Our approach offers a powerful method for the study of intramolecular changes or complex formation using FRET at the single-cell level in live bacteria.

Spatial recovery of the murine gut microbiota after antibiotics perturbation.

Bacterial communities are highly complex, with interaction networks dictating ecosystem function. Bacterial interactions are constrained by the spatial organization of these microbial communities, yet studying the spatial organization of microbial communities at the single-cell level has been technically challenging. Here, we use the recently developed high-phylogenetic-resolution microbiota mapping by fluorescence in situ hybridization technology to image the gut microbiota at the species and single-cell level. We simultaneously image 63 different bacterial species to spatially characterize the perturbation and recovery of the gut microbiota to ampicillin and vancomycin in the cecum and distal colon of mice. To decipher the biology in this complex imaging data, we developed an analytical framework to characterize the spatial changes of the gut microbiota to a perturbation. The three-tiered analytical approach includes image-level diversity, pairwise colocalization analysis, and hypothesis-driven neighborhood analysis. Through this workflow, we identify biogeographic and antibiotic-based differences in the spatial organization of the gut microbiota. We demonstrate that the cecal microbiota has increased micrometer-scale diversity than the colon at baseline and recovers better from perturbation. Also, we identify potential foundation and keystone species that have high baseline neighborhood richness and that are associated with recovery from antibiotics. Through this workflow, we add a spatial layer to the characterization of bacterial communities and progress toward a better understanding of bacterial interactions leading to improved microbiome modulation strategies. IMPORTANCE: Antibiotics have broad off-target effects on the gut microbiome. When the microbial community is unable to recover from antibiotics, it can lead to increased susceptibility to gastrointestinal infections and increased risk of immunological and metabolic diseases. In this study, we work to better understand how the gut microbiota recovers from antibiotics by employing a recent technology to image the entire bacterial community at once. Through this approach, we characterize the spatial changes in the gut microbiota after treatment with model antibiotics in both the cecum and colon of mice. We find antibiotic- and biogeographic-dependent spatial changes between bacterial species and that many of these spatial colocalizations do not recover to baseline levels even 35 days after antibiotic administration.

A retrospective analysis of outcomes and complications of living- and deceased-donor split-liver transplantation in Johannesburg, South Africa.

BACKGROUND: South African transplant centres are faced with significant challenges in meeting the need for liver transplantation, owing to the low and ever-decreasing number of deceased-donor organs. To increase organ utility, deceased-donor split-liver transplant (DDSLT) and living-donor liver transplant (LDLT) programmes were initiated in the Wits Transplant Unit. OBJECTIVE: To evaluate outcomes of the LDLT and DDSLT programmes. METHODS: A retrospective analysis of de-identified recipient and donor variables from all adult and paediatric DDSLTs and LDLTs conducted between 2013 and 2021 was performed. Comparison of categorical study variables between graft types was done with the χ2 test. Continuous variables were compared by means of the independent samples t-test. Cox proportional hazards regression was performed to examine the effect of graft type on recipient and graft survival. All comparisons were made unadjusted, and adjusted for recipient age, recipient ethnicity, donor sex, and graft-weight-to-recipient-weight ratio (GWRWR) (for the paediatric cohort); and for donor age and GWRWR (for the adult cohort). RESULTS: A total of 181 paediatric and 48 adult liver transplants have been performed since the inception of the two programmes. Chronic liver failure, specifically intra- and extrahepatic cholestatic disease, was our main indication for liver transplantation in both cohorts. There were no significant differences between the DDSLTs and LDLTs in respect of pre- or post-discharge intervention, in-hospital mortality, length of stay, and recipient or graft survival within both the paediatric and adult groups. Our overall 1- and 3-year survival estimates (95% confidence intervals) were 77% (70% - 83%) and 71% (64% - 78%) for the paediatric cohort, and 77% (62% - 87%) and 66% (50% - 78%) for the adult cohort, respectively. CONCLUSION: The results of this study demonstrate comparable outcomes between DDSLT and LDLT, indicating that both methods are effective approaches to optimise organ utilisation for liver transplantation within our setting.

Bacterial attachment on sub-nanometrically smooth titanium substrata.

Despite the volume of work that has been conducted on the topic, the role of surface topography in mediating bacterial cell adhesion is not well understood. The primary reason for this lack of understanding is the relatively limited extent of topographical characterisation employed in many studies. In the present study, the topographies of three sub-nanometrically smooth titanium (Ti) surfaces were comprehensively characterised, using nine individual parameters that together describe the height, shape and distribution of their surface features. This topographical analysis was then correlated with the adhesion behaviour of the pathogenic bacteria Staphylococcus aureus and Pseudomonas aeruginosa, in an effort to understand the role played by each aspect of surface architecture in influencing bacterial attachment. While P. aeruginosa was largely unable to adhere to any of the three sub-nanometrically smooth Ti surfaces, the extent of S. aureus cell attachment was found to be greater on surfaces with higher average, RMS and maximum roughness and higher surface areas. The cells also attached in greater numbers to surfaces that had shorter autocorrelation lengths and skewness values that approached zero, indicating a preference for less ordered surfaces with peak heights and valley depths evenly distributed around the mean plane. Across the sub-nanometrically smooth range of surfaces tested, it was shown that S. aureus more easily attached to surfaces with larger features that were evenly distributed between peaks and valleys, with higher levels of randomness. This study demonstrated that the traditionally employed amplitudinal roughness parameters are not the only determinants of bacterial adhesion, and that spatial parameters can also be used to predict the extent of attachment.

Morbidity and mortality in adult spinal deformity surgery: Norwich Spinal Unit experience.

PURPOSE: This study analyses the complications of spinal deformity surgery in adults to highlight pre-disposing factors. METHODS: The clinical records and imaging were reviewed for 48 consecutive patients, 12 males and 36 females, with a mean age of 64 (31-86), who had surgery for spinal deformity. Mean follow-up time was 36 months (24-60). Patient data recorded were age, diagnosis and co-morbidities; deformity assessment: curve type, sagittal and coronal balance, Cobb angle. Operation details: number of instrumented levels, duration and intra-operative complications. OUTCOME: complications, re-operations, balance and Cobb angle. RESULTS: 28 patients (58 %) had at least 1, 15 patients (27 %) had 2 and 5 patients (9.5 %) had more than 2 co-morbidities. Average time between 1st presentation and operation was 13 months (1-41). The mean number of levels fused was 10.8 (4-23). In addition to posterior pedicle screw instrumentation, 40 patients had chevron osteotomies and 8 had pedicle substraction osteotomies. Posterior interbody fusions were performed at one level in 17 of which 7 had 2 level fusion. Two patients had combined anterior and posterior approaches. Fusion to the pelvis was performed in 19 patients. There were a total of 27 major and minor complications in 19/48 (39.5 %) patients. Late complications included 5 patients who had revisions for proximal junctional kyphosis, 1 patient had revision for pseudoarthrosis and 4 patients had removal of mal-positioned screws. CONCLUSIONS: Factors associated with high complication rate in adult spinal deformity surgery are age, co-morbidities and severe sagittal imbalance at the time of presentation.

Non-destructive evaluation of articular cartilage defects using near-infrared (NIR) spectroscopy in osteoarthritic rat models and its direct relation to Mankin score.

OBJECTIVE: The aim of this study was to demonstrate the potential of near-infrared (NIR) spectroscopy for categorizing cartilage degeneration induced in animal models. METHOD: Three models of osteoarthritic degeneration were induced in laboratory rats via one of the following methods: (1) menisectomy (MSX); (2) anterior cruciate ligament transection (ACLT); and (3) intra-articular injection of mono-ido-acetate (1 mg) (MIA), in the right knee joint, with 12 rats per model group. After 8 weeks, the animals were sacrificed and tibial knee joints were collected. A custom-made near-infrared (NIR) probe of diameter 5 mm was placed on the cartilage surface and spectral data were acquired from each specimen in the wave number range 4,000-12,500 cm(-1). Following spectral data acquisition, the specimens were fixed and Safranin-O staining was performed to assess disease severity based on the Mankin scoring system. Using multivariate statistical analysis based on principal component analysis and partial least squares regression, the spectral data were then related to the Mankin scores of the samples tested. RESULTS: Mild to severe degenerative cartilage changes were observed in the subject animals. The ACLT models showed mild cartilage degeneration, MSX models moderate, and MIA severe cartilage degenerative changes both morphologically and histologically. Our result demonstrates that NIR spectroscopic information is capable of separating the cartilage samples into different groups relative to the severity of degeneration, with NIR correlating significantly with their Mankin score (R(2) = 88.85%). CONCLUSION: We conclude that NIR is a viable tool for evaluating articular cartilage health and physical properties such as change in thickness with degeneration.

Improvements in survival of gynaecological cancer in the Anglia region of England: are these an effect of centralisation of care and use of multidisciplinary management?

OBJECTIVE: Our hypothesis is that the adoption of Department of Health (DH) guidance has led to an improvement in outcome in gynaecological cancer survival. SETTING: In 1999 the DH in England introduced the Improving Outcomes in Gynaecological Cancer guidance, advising case management by multidisciplinary teams with surgical concentration in specialist hospitals. This guidance was rapidly adopted in the East of England, with a population of 2.5 million. POPULATION: The population of the Anglia Cancer Network was approximately 2.3 million. METHODS: From 1996 to 2003, details of 3406 cases of gynaecological cancer were identified in the Anglia region of England. Survival analysis was performed by Cox proportional hazards regression, relative to cases diagnosed in 1996. MAIN OUTCOME MEASURE: Primary endpoint was survival. RESULTS: The survival rates for cases diagnosed between 1996 and 1999 were broadly the same across the time period, with a marked improvement taking place in 2000, and continuing to 2003 (HR 0.71, 95% CI 0.64-0.79, comparing 2000-03 with 1996-99 diagnoses), for all gynaecological sites combined. Adjustment for treatments or method of case follow-up did not attenuate these improvements. There was a concurrent change towards major surgery being performed in specialist centres from 2000. CONCLUSIONS: The adoption of the 1999 guidance on gynaecological cancer, which included multidisciplinary case management and centralisation of surgery, resulted in a marked step-change improvement in survival of gynaecological cancer in an area of eastern England in 2000.

Air-directed attachment of coccoid bacteria to the surface of superhydrophobic lotus-like titanium.

Superhydrophobic titanium surfaces fabricated by femtosecond laser ablation to mimic the structure of lotus leaves were assessed for their ability to retain coccoid bacteria. Staphylococcus aureus CIP 65.8T, S. aureus ATCC 25923, S. epidermidis ATCC 14990T and Planococcus maritimus KMM 3738 were retained by the surface, to varying degrees. However, each strain was found to preferentially attach to the crevices located between the microscale surface features. The upper regions of the microscale features remained essentially cell-free. It was hypothesised that air entrapped by the topographical features inhibited contact between the cells and the titanium substratum. Synchrotron SAXS revealed that even after immersion for 50 min, nano-sized air bubbles covered 45% of the titanium surface. After 1 h the number of cells of S. aureus CIP 65.8T attached to the lotus-like titanium increased to 1.27×10(5) mm(-2), coinciding with the replacement of trapped air by the incubation medium.