Patient-reported outcome after hallux valgus surgery - a two year follow up.

BACKGROUND: Patients with hallux valgus deformity may require surgery but prospective patient-reported data is scarce. METHODS: We evaluated 53 patients with a mean age of 55.3years (SD 14.1, 50 women), who underwent surgery due to hallux valgus. They completed the PROMs SEFAS, EQ-5D and SF-36 before and 6, 12 and 24 months after surgery. RESULTS: All patient-reported outcomes improved at 6, 12 and 24months compared with the preoperative status. The greatest improvement occurred at 6months: SEFAS Δ 10.0 (95% confidence interval 7.8-12.2), EQ-5D Δ 0.22 (0.15-0.29), EQ-VAS Δ 8.4 (4.4-12.4), PF SF-36 Δ 22.0 (14.6-29.3) and BP SF-36 Δ 30.6 (23.1-38.1). CONCLUSIONS: Hallux valgus surgery considerably reduced pain and improved function already within 6months after surgery. The improvement between 6 and 24months' follow-up was minimal measured with PROMs. LEVEL OF CLINICAL EVIDENCE: III - prospective observational cohort study.

Extended physical education in children aged 6-15 years was associated with improved academic achievement in boys.

AIM: Physical activity (PA) has been associated with enhanced cognition, brain development and concentration. This study evaluated whether increased physical education (PE) improved academic achievement. METHODS: We recruited 304 children (55% boys) from a Swedish school in Skane County in 1998-2002 when they were six to seven years of age and followed them through all nine mandatory school years. Their PE level was increased from 60 to 200 minutes per week, and their results were compared with 73 885 control children (51% boys) in the county who graduated in the same years and did the standard 60 minutes of PE per week. Their academic achievements were measured as their final grade scores and the proportion of students eligible for upper secondary school. RESULTS: The eligibility for further education increased in the intervention boys by 6.8 percentage points and the mean grade score by 12.1 points, while in the control group as a whole, the eligibility rate decreased by 0.7 percentage points and the mean grade score increased by 1.7 points. No changes in eligibility rates or mean grade scores were seen in the intervention girls. CONCLUSION: Increasing weekly PE over nine years was associated with improved academic achievement in boys.

Dichloro-naphthoquinone as a non-classical inhibitor of the mycobacterial carbonic anhydrase Rv3588c.

The soluble mycobacterial carbonic anhydrases Rv3588c and Rv1284 belong to a different class of carbonic anhydrases than those found in humans, making them attractive drug targets by using the inherent differences in the folds of the different classes. By screening a natural product library, we identified naphthoquinone derivatives as a novel non-classical inhibitor scaffold of mycobacterial carbonic anhydrases that lack the sulfonamide/sulfamate group and thus did not affect human carbonic anhydrase II.

The associations of physical activity with fracture risk--a 7-year prospective controlled intervention study in 3534 children.

SUMMARY: This is the first study indicating an association between gradually diminished risk of fractures and years of increased physical activity. Our results could imply great benefits not only for the individual but also for the healthcare burden and cost of society. INTRODUCTION: Physical activity (PA) in childhood is associated with high bone mass and beneficial neuromuscular function. We investigate if increased PA also is associated with fracture risk. METHODS: We registered fractures in 3534 children aged 6 to 8 years at study start for up to 7 years; 1339 with 40 min of moderate PA every school day (intervention) and 2195 with the Swedish standard curriculum of 60 min of PA per school week (controls). In a subsample of 264 children, we measured areal bone mineral density (aBMD; g/cm(2)) with dual-energy X-ray absorptiometry (femoral neck and total spine) and muscle strength (peak torque for knee extension and flexion; Nm) with computerized dynamometer at baseline and after 7 years. We estimated annual fracture incidence rate ratios (IRR) in the intervention group compared to the control group as well as changes in bone mass and muscle strength. Data is given as mean (95% CI). RESULTS: The IRR of fractures decreased with each year of the PA intervention (r = -0.79; p = 0.04). During the seventh year, IRR was almost halved [IRR 0.52 (0.27, 1.01)]. The intervention group had a statistically significant greater gain in total spine aBMD with a mean group difference of 0.03 (0.00, 0.05) g/cm(2) and peak flexion torque 180° with a mean group difference of 5.0 (1.5, 8.6) Nm. CONCLUSIONS: Increased PA is associated with decreased fracture risk, probably in part due to beneficial gains in aBMD and muscle strength.

Surgery for adult acquired flatfoot due to posterior tibial tendon dysfunction reduces pain, improves function and health related quality of life.

BACKGROUND: Patients with adult acquired flatfoot deformity (AAFD) due to posterior tibial tendon dysfunction (PTTD) may require surgery but few reports have evaluated the outcome. METHODS: We evaluated 21 patients with a median age of 60 (range 37-72) years who underwent different surgical reconstructions due to stage II AAFD before and 6 and 24 months after surgery by the validated Self-Reported Foot and Ankle Score (SEFAS), Short Form 36 (SF-36) and Euroquol 5 Dimensions (EQ-5D). RESULTS: The improvement from before to 24 months after surgery was in SEFAS mean 12 (95% confidence interval 8-15), SF-36 physical function 21 (10-22), SF-36 bodily pain 28 (17-38), EQ-5D 0.2 (0.1-0.3) and EQ-VAS 11 (2-21). CONCLUSION: Surgery for AFFD due to PTTD results in reduced pain and improved function and health related quality of life. The outcome scores have been demonstrated as useful. It has also been shown, since there is a further improvement between 6 and 24 months after surgery, that a minimum follow-up of 2 years is needed. LEVEL OF CLINICAL EVIDENCE: III - prospective observational cohort study.

The lens of the eye: exposures in the UK medical sector and mechanistic studies of radiation effects.

The recommendation from the International Commission on Radiological Protection that the occupational equivalent dose limit for the lens of the eye should be reduced to 20 mSv year(-1), averaged over 5 years with no year exceeding 50 mSv, has stimulated a discussion on the practicalities of implementation of this revised dose limit, and the most appropriate risk and protection framework to adopt. This brief paper provides an overview of some of the drivers behind the move to a lower recommended dose limit. The issue of implementation in the medical sector in the UK has been addressed through a small-scale survey of doses to the lens of the eye amongst interventional cardiologists and radiologists. In addition, a mechanistic study of early and late post-irradiation changes in the lens of the eye in in-vivo-exposed mice is outlined. Surveys and studies such as those described can contribute to a deeper understanding of fundamental and practical issues, and therefore contribute to a robust evidence base for ensuring adequate protection of the eye while avoiding undesirable restrictions to working practices.

Bone mass and anthropometry in patients with osteoarthritis of the foot and ankle.

BACKGROUND: Patients with hip and knee osteoarthritis (OA) have high bone mineral density (BMD) and high BMI. If the same accounts for patients with foot or ankle OA is unknown. METHODS: We measured BMD and femoral neck (FN) width by dual-energy X-ray absorptiometry in 42 women and 19 men with idiopathic OA in the foot or ankle, and in 99 women and 82 men as controls. RESULTS: Women with OA had significant higher BMI than controls. Women with OA had higher BMI-adjusted BMD (p<0.01) and smaller BMI-adjusted FN width (p<0.01) than controls. Men with OA had higher BMI adjusted-BMD (p<0.05) and smaller BMI-adjusted FN width (p<0.01) than controls. CONCLUSION: Patients with OA in the foot or ankle have higher BMD and smaller bone size than being expected by their BMI. This phenotype may provide unfavourable forces across the joint and is hypothetically important for development of OA.

Diketoacid inhibitors of HIV-1 integrase: from L-708,906 to raltegravir and beyond.

HIV-1 integrase is one of the three viral enzymes essential to HIV replication. Consequently the development of therapeutics targeting this enzyme has been a major focus of antiretroviral research over the past two decades. Several classes of integrase inhibitors have been identified; of these the diketoacids (DKAs) show greatest promise: raltegravir (Merck & Co) has been approved by the US Food and Drug Administration (FDA) for HIV-1 therapy, while elvitegravir (Gilead Sciences/ Japan Tobacco) has reached phase III clinical trials. This review considers the development of DKA-based inhibitors from early screening studies through to the release of raltegravir. SAR data collated from numerous studies are compared and analysed, shedding light on the geometric and electronic requirements for effective binding to HIV-1 integrase. This information will in turn aid the rational design of future generations of integrase inhibitors.

Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist in the unilateral 6-OHDA lesion rat model.

The degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease (PD) is associated with altered transmission at striatal NMDA receptors containing NR2B subunits. We investigated a potential novel therapeutic compound, 4-trifluoromethoxy-N-(2-trifluoromethyl-benzyl)-benzamidine (BZAD-01), a selective NMDA NR1A/2B receptor antagonist for PD and compared it with levodopa, the standard treatment for PD. This study also evaluated whether combining levodopa and BZAD-01 gave better improvements of parkinsonian symptoms. Parkinsonism was induced by microinjection of the toxin, 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) of 40 Sprague-Dawley rats. Parkinsonism and the efficacy of drugs were assessed using a battery of behavioural tests including balance beam, apomorphine-induced rotation, body axis bias or "curling", head position bias and disengage sensorimotor latency test. Immunohistochemistry was performed on post-mortem tissue to estimate the loss of dopaminergic neurons. The main effects were that BZAD-01 co-administration prevented chronic levodopa-induced potentiation of apomorphine rotation. However levodopa-treated rats were slower than either controls or BZAD-01-treated rats in the locomotor test. The improvement in the apomorphine rotation test suggests that BZAD-01 may be a useful adjunct to levodopa monotherapy.

Behavioural effects of a selective NMDA NR1A/2B receptor antagonist in rats with unilateral 6-OHDA+parafascicular lesions.

Experimental lesions involving the parafascicular (Pf) nucleus and medial forebrain bundle (MFB) may model to some extent the pathological loss of glutamatergic neurons from the centromedian-parafascicular (CM-Pf) complex and nigral dopaminergic cell loss observed clinically at post-mortem in Parkinson's disease (PD) cases. Our study investigated whether there were alterations in symptomatology in such rats with unilateral 6-OHDA+Pf lesions after treatment with either a selective NR1A/NR2B NMDA antagonist and/or l-dopa. Rats were given dual surgery to the MFB with 6-hydroxydopamine (6-OHDA) and Pf with N-methyl-d-aspartate (NMDA). (i) An NR1A/NR2B selective NMDA antagonist (BZAD-01; 10mg/kg), (ii) l-dopa (25mg/kg), (iii) BZAD-01+l-dopa (10mg/kg; 25mg/kg) or (iv) vehicle solution were administered for 6 weeks, during which behavioural testing was performed. BZAD-01 improved postural asymmetry in the first month as well as apomorphine-induced rotation. The latter was also improved by l-dopa in this model. These data support the use of selective NR1/NR2B NMDA antagonists in the therapeutics of PD.

Genetic determinants modulate susceptibility to pregnancy-associated tumourigenesis in a recombinant line of Min mice.

Min mice provide a good model of human familial adenomatous polyposis. Recently, we have reported on two recombinant inbred lines (I and V) and the location of a modifier (Mom3) close to Apc, which altered polyp numbers in our mice possibly by modifying the frequency of wild-type (WT) allele loss at Apc; mice with severe disease (line V) showed elevated rates of loss. We now show that in line I only, a single pregnancy caused a significant increase in adenoma multiplicity compared with virgin controls (P<0.001) and that an additional pregnancy conferred a similar risk. Pregnancy was linked to both adenoma initiation and enhanced tumour growth in line I mice, and interline crosses indicated that susceptibility to pregnancy-associated adenomas was under genetic control. We found no evidence for the involvement of oestrodial metabolizing genes or the oestrogen receptors (Esr1 and 2) in tumour multiplicity. Importantly, a significantly elevated frequency of WT allele loss at Apc was observed in adenomas from parous mice (line and backcrossed) carrying the line I Min allele relative to equivalent virgin controls (P=0.015). Our results provide the first experimental evidence for genetic determinants controlling pregnancy-associated tumourigenesis; analogous genetic factors may exist in humans.

Evidence for complex multigenic inheritance of radiation AML susceptibility in mice revealed using a surrogate phenotypic assay.

The mapping of genes which affect individual cancer risk is an important but complex challenge. A surrogate assay of susceptibility to radiation-induced acute myeloid leukaemia (AML) in the mouse based on chromosomal radiosensitivity has been developed and validated. This assay was applied to the mapping of radiation-induced AML risk modifier loci by association with microsatellite markers. A region on chromosome (chr) 18 with strong association is identified and confirmed by backcross analysis. Additional loci on chrs 8 and 13 show significant association. A key candidate gene Rbbp8 on chr18 is identified. Rbbp8 is shown to be upregulated in response to X-irradiation in the AML sensitive CBA strain but not AML resistant C57BL/6 strain. This study demonstrates the strength of utilizing surrogate endpoints of cancer susceptibility in the mapping of mouse loci and identifies additional loci that may affect radiation cancer risk.

User-controlled photographic animations, photograph-based questions, and questionnaires: three Internet-based instruments for measuring drivers' risk-taking behavior.

The Internet has been exploited successfully in the past as a medium for behavioral research. This paper presents a series of studies designed to assess Internet-based measures of drivers' risk-taking behavior. First, we compared responses from an Internet sample with a traditional pencil-and-paper sample using established questionnaire measures of risk taking. No significant differences were found. Second, we assessed the validity of new Internet-based instruments, involving photographs and photographic animations, that measured speed, gap acceptance, and passing. Responses were found to reflect known demographic patterns of actual behavior to some degree. Also, a roadside survey of speeds was carried out at the locations depicted in the photographic measure of speeding and, with certain exceptions, differences between the two appeared to be constant. Third, a between-subject experimental manipulation involving the photographic animation measure of gap acceptance was used to demonstrate one application of these techniques.

Automatic morphological sieving: comparison between different methods, application to DNA ploidy measurements.

The aim of the present study is to propose alternative automatic methods to time consuming interactive sorting of elements for DNA ploidy measurements. One archival brain tumour and two archival breast carcinoma were studied, corresponding to 7120 elements (3764 nuclei, 3356 debris and aggregates). Three automatic classification methods were tested to eliminate debris and aggregates from DNA ploidy measurements (mathematical morphology (MM), multiparametric analysis (MA) and neural network (NN)). Performances were evaluated by reference to interactive sorting. The results obtained for the three methods concerning the percentage of debris and aggregates automatically removed reach 63, 75 and 85% for MM, MA and NN methods, respectively, with false positive rates of 6, 21 and 25%. Information about DNA ploidy abnormalities were globally preserved after automatic elimination of debris and aggregates by MM and MA methods as opposed to NN method, showing that automatic classification methods can offer alternatives to tedious interactive elimination of debris and aggregates, for DNA ploidy measurements of archival tumours.

Influence of sample size on image cytometry of DNA ploidy measurements.

OBJECTIVE: To assess the number of nuclei required for significant image cytometry DNA ploidy measurements on one archival case of breast cancer. STUDY DESIGN: From one case of aneuploid DNA breast cancer, 18 subsets made up of 152-1,524 for the whole population of undamaged nuclei and made up of 74-735 epithelial nuclei had DNA measured. DNA ploidy type and five DNA ploidy indices, allowing DNA ploidy histogram interpretation were evaluated on each population. RESULTS: Three hundred nuclei were always sufficient for DNA typing, whereas reliable results for DNA ploidy indices required at least 750 nuclei. CONCLUSION: To DNA measure the above number of nuclei, fully automated image cytometry DNA ploidy measurements are required.

Assessment of fibre orientation in reinforced concrete using Fourier image transform.

In this study, ribbon-shaped amorphous cast-iron fibres were used to reinforce a concrete matrix. X-ray photographs have been taken to detect fibres in situ. Their orientation has been investigated by automatic image analysis methods. However, this measurement should not be influenced by the digitization on the square frame of the analyser. For that purpose, the Fourier transform was used rather than the rose of direction method. This analysis revealed the transverse isotropic nature of the spatial arrangement of these fibres, whose axis of revolution corresponds to the concrete casting axis. Such a morphological characterization of the fibre-reinforced concrete reveals its mechanical behaviour.

Influence of debris and aggregates on image cytometry DNA measurement of archival tumors.

OBJECTIVE: To investigate, for seven samples, the influence of unwanted elements (e.g., remains of erythrocyte cell membranes, sliced nuclei, damaged nuclei and aggregates) on image cytometry DNA ploidy measurements. STUDY DESIGN: Two normal reference tissues (brain and breast), one breast cancer and four brain tumors were studied. For each sample, the influence of the different classes of debris on DNA ploidy histograms and indices was evaluated. RESULTS: The influence differs regarding each class of debris and the index to be evaluated. CONCLUSION: Strict and precise elimination of debris and aggregates is required. Moreover, strategies and efforts that must be applied to automated elimination of these unwanted elements must be a direct function of the bias they introduce into DNA ploidy measurements.

Anal tenesmus caused by seminal vesicle cyst.

Congenital cysts of the seminal vesicles with ipsilateral renal aplasia or dysplasia are rare but have been well described in the literature. We report the first case where anal tenesmus was the only presenting symptom. Another unique feature was the combination of this anomaly with a duplication of the inferior vena cava.

Clinical observations of adult intercountry adoptees and their adoptive parents.

This article presented data from interviews with 29 adult foreign-born adoptees and 23 adoptive parents, highlighting M.S.W. students' impressions of the interviewees' responses. The students' main observations stressed individualizing adoptees and their families, cautioning against falling into the all-too-easy trap of self-fulfilling labeled behavior. A second theme was the importance of each social worker's own sensitivity and attitudes toward this type of racial mixing, and emphasized professional and personal self-awareness.