Virtual reality simulation for mastery learning of wrist radiograph technique.

INTRODUCTION: Virtual reality (VR) simulation is a technology that empowers students and radiographers to practice radiography in a virtual environment that resembles real-life clinical scenarios. The purpose of this randomised study was to examine the relationship between clinical specialty and the ability to assess and obtain a lateral wrist radiograph using a VR simulator. METHODS: Radiographers and radiography students were recruited from the EFRS Research Hub at the 2024 European Congress of Radiology. After completing a background questionnaire, participants entered a VR simulator where they assessed lateral wrist radiographs and, if necessary, attempted a retake. Fisher's exact test was used to evaluate the relationship between specialties and participants' ability to assess positioning and perform retakes. Rank-biserial correlation estimated the relationship between participants' ability to reposition the VR patient and their VR experience and self-perceived confidence in wrist radiograph positioning. RESULTS: The cohort included 173 participants from 14 specialties across 21 countries. There was a borderline significant trend between clinical specialty and correct positioning assessment (p = 0.052) and between self-perceived confidence in acquiring wrist radiographs and repositioning for a retake (p = 0.052). Neither clinical specialty (p = 0.480) nor previous VR experience (p = 0.409) correlated with ability to reposition for a retake. CONCLUSION: While results indicated a potential correlation between participants' ability to position a VR patient and both clinical specialty and confidence in wrist radiography, these trends were not statistically significant. Nevertheless, the findings suggest that VR holds promise for radiography training, though further research is necessary to explore the factors that influence performance and learning. IMPLICATIONS FOR PRACTICE: The incorporation of VR technology into standard radiography training programs could potentially improve patient outcomes by ensuring that radiography students are more skilled at acquiring quality radiographs prior to their first clinical practice. It should be noted though, that knowledge on positioning criteria and anatomy is an advantage when practicing correct positioning in a VR simulator.

Psychological interventions improve quality of life despite persistent pain in endometriosis: results of a 3-armed randomized controlled trial.

PURPOSE: Despite standard medical treatment endometriosis is often associated with disabling pain and poor quality of life (QoL). Studies indicate that psychological interventions (PIs) may improve pain and QoL, yet studies on the effects of PIs for women with endometriosis are sparse and limited by low-quality study designs. Therefore, this study aimed, in a rigorous three-armed design, to evaluate the effect of PIs on chronic pelvic pain (CPP) and QoL in women with endometriosis. METHODS: This three-armed parallel, multi-center randomized controlled trial included fifty-eight endometriosis patients reporting severe CPP [≥ 5 for pain intensity measured on a 0-10-point numeric rating scale (NRS)]. Patients were randomly assigned to (1) Specific mindfulness- and acceptance-based psychological intervention (MY-ENDO), (2) Carefully matched non-specific psychological intervention (Non-specific), or (3) A wait-list control group (WL). The primary outcome was pelvic pain intensity/unpleasantness measured on NRS. Secondary outcomes included endometriosis-related quality of life, workability, pain acceptance, and endometriosis-related symptoms. Differences in outcomes between groups at post-treatment follow-up were analyzed using mixed linear models. Analyses were performed on an intention-to-treat basis. RESULTS: Compared to WL, psychological intervention (MY-ENDO + Non-specific) did not significantly reduce pain. However, psychological intervention did significantly improve the QoL-subscales 'control and powerlessness', 'emotional well-being', and 'social support' as well as the endometriosis-related symptoms 'dyschezia' and 'constipation'. MY-ENDO was not superior to Non-specific. CONCLUSIONS: Women with endometriosis may have significant and large effects of psychological intervention on QoL despite an ongoing experience of severe CPP. TRIAL REGISTRATION: 12 April 2016, clinicaltrials.gov (NCT02761382), retrospectively registered.

Health-related quality of life in women with endometriosis: psychometric validation of the Endometriosis Health Profile 30 questionnaire using confirmatory factor analysis.

STUDY QUESTION: Which of the competing models of the Endometriosis Health Profile 30 Questionnaire (EHP-30) factor structure is best supported by confirmatory factor analysis (CFA)? SUMMARY ANSWER: Findings support a five-factor first-order model of the EHP-30, thereby lending support to the model originally suggested by the questionnaire developers. WHAT IS KNOWN ALREADY: Endometriosis has a negative impact on quality of life, and measures specifically developed to address this impact, such as the EHP-30, are vital in research and disease management. Previous studies have found different models of the EHP-30 factor structure, and generated uncertainty regarding how to use the questionnaire. CFA can be applied to compare competing factor models and determine the underlying structure of a questionnaire. STUDY DESIGN SIZE DURATION: This cross-sectional multicenter study included 304 women with endometriosis recruited from three different public health service endometriosis clinics (referral centers for treatment of severe endometriosis) and the Danish Endometriosis Patients Association from 2014 to 2015. PARTICIPANTS/MATERIALS SETTING METHODS: Diagnosis of endometriosis was confirmed in medical records for 84.2% and by histology for 66.8% of participants. Questionnaires (the licensed Danish version of the EHP-30) were sent by post two times with a 6- to 12-week interval. CFA was used to examine construct validity and Bland-Altman plots to examine test-retest reliability and the convergent validity with the Short Form 36 version 2. MAIN RESULTS AND THE ROLE OF CHANCE: Response rate was high (87.6%). CFA supported the original first-order five-factor structure of the EHP-30, and thereby, the use of five separate scale-scores in clinical and research practice. Visual inspection of Bland-Altman plots suggested excellent test-retest reliability of the EHP-30 and supported the use of a disease specific quality of life instrument for women with endometriosis. LIMITATIONS REASONS FOR CAUTION: Diagnosis could not be confirmed through histology data in 33.2% of participants. However, subgroup analyses based on women with confirmed histology only, yielded similar results. Data related to menstrual cycle stage and the use of hormonal and pain medication during questionnaire completion were not collected. A larger study, including data from different countries on different continents, would be better designed to exclude potential population bias. WIDER IMPLICATIONS OF THE FINDINGS: EHP-30, with its original five-factor structure, appears to be a valid, stable, and specific quality of life measure for women with endometriosis. It seems easy to understand, quick to administer, and importantly, scoring might be unaffected by cyclical/menstrual pain symptoms related to endometriosis. The finding of a five-factor model from different studies across several countries supports the crosscultural validity of the EHP-30. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Danish Endometriosis Association, which is a nongovernmental organization run by women with endometriosis and by a scholarship from the Health Research Fund of Central Denmark Region. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: The Danish Data Protection Agency (J.nr: 2013-41-2264).

Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease.

Doctors do not know whether treatment of high parathyroid hormone levels is linked to better outcomes in their patients with kidney disease. In this study, lower parathyroid hormone levels at baseline were linked to lower risk of fracture, vascular events, and death in people with kidney disease. PURPOSE: Chronic kidney disease (CKD) affects ~ 20% of older adults, and secondary hyperparathyroidism (HPT) is a common condition in these patients. To what degree HPT predicts fractures, vascular events, and mortality in pre-dialysis CKD patients is debated. In stage 3 and 4 CKD patients, we assessed relationships between baseline serum PTH levels and subsequent 10-year probabilities of clinical fractures, vascular events, and death. METHODS: We used Marshfield Clinic Health System electronic health records to analyze data from adult CKD patients receiving care between 1985 and 2013, and whose PTH was measured using a second-generation assay. Covariates included PTH, age, gender, tobacco use, vascular disease, diabetes, hypertension, hyperlipidemia, obesity, GFR, and use of osteoporosis medications. RESULTS: Five thousand one hundred eight subjects had a mean age of 68 ± 17 years, 48% were men, and mean follow-up was 23 ± 10 years. Fractures, vascular events, and death occurred in 18%, 71%, and 56% of the cohort, respectively. In univariate and multivariate models, PTH was an independent predictor of fracture, vascular events, and death. The hazards of fracture, vascular events and death were minimized at a baseline PTH of 0, 69, and 58 pg/mL, respectively. CONCLUSIONS: We found that among individuals with stage 3 and 4 CKD, PTH was an independent predictor of fractures, vascular events, and death. Additional epidemiologic studies are needed to confirm these findings. If a target PTH range can be confirmed, then randomized placebo-controlled trials will be needed to confirm that treating HPT reduces the risk of fracture, vascular events, and death.

A mixture of Persistent Organic Pollutants (POPs) and Azoxymethane (AOM) show potential synergistic effects on intestinal tumorigenesis in the A/J Min/+ mouse model.

A multitude of cancer types, including breast, testicular, liver and colorectal cancer, have associations with exposure to Persistent Organic Pollutants (POPs). The present study aimed to investigate whether a mixture of POPs could affect intestinal tumorigenesis in the A/J Min/+ mouse, a model for human colorectal cancer (CRC). Pollutants were selected for their presence in Scandinavian food products and the mixture was designed based on defined human estimated daily intake levels. Mice were exposed through the diet, at control, low and high mixture concentrations, for 10 weeks. In a separate experiment, mice also received one subcutaneous injection of Azoxymethane (AOM) to explore whether this carcinogenic compound influenced the effect of the POPs. Intestinal tumorigenesis was examined by surface microscopy and histopathology. Moderate and dose-dependent increases in tumorigenesis were observed after dietary POP exposure. The AOM treatment alone stimulated the growth of colonic lesions, but did not increase the formation of new lesions. Combined AOM treatment and POP exposure demonstrated a synergistic effect on lesion formation in the colon, and to a lesser extent in the small intestine. This synergy was also evident by an increased number of malignant colonic tumors (carcinomas). In conclusion, the study shows that a mixture of POPs interacted synergistically with a known carcinogen (AOM), causing increased intestinal tumorigenesis in the A/J Min/+ mouse model.

DXA Errors Are Common and Reduced by Use of a Reporting Template.

OBJECTIVE: High quality dual energy X-ray absorptiometry (DXA) acquisition, analysis, and reporting demands technical and interpretive excellence. We hypothesized that DXA errors are common and of such magnitude that incorrect clinical decisions might result. In this 2-phase study, we evaluated DXA technical and interpretation error rates in a clinical population and subsequently assessed if implementing an interpretation template reduced errors. METHODS: In phase 1, DXA scans of 345 osteoporosis clinic referrals were reviewed by International Society for Clinical Densitometry-certified technologists (n = 3) and physicians (n = 3). Technologists applied International Society for Clinical Densitometry performance standards to assess technical quality. Physicians assessed reporting compliance with published guidance, relevance of technical errors and determined overall and major error prevalence. Major errors were defined as "provision of inaccurate information that could potentially lead to incorrect patient care decisions." In phase 2, a DXA reporting template was implemented at 2 clinical DXA sites after which the 3 physicians reviewed 200 images and reports as above. The error prevalence was compared with the 298 patients in phase 1 from these sites. RESULTS: In phase 1, technical errors were identified in 90% of patients and affected interpretation in 13%. Interpretation errors were present in 80% of patients; 42% were major. The most common major errors were reporting incorrect information on bone mineral density change (70%) and incorrect diagnosis (22%). In phase 2, at these 2 clinical sites, major errors were present in 37% before and 17% after template implementation. Template usage reduced the odds of major error by 66% (odds ratio 0.34, 95% confidence interval 0.21, 0.53, and p < 0.0001). CONCLUSION: DXA technical and interpretation errors are extremely common and likely adversely affect patient care. Implementing a DXA reporting template reduces major errors and should become common practice. Additional interventions, such as requiring initial and ongoing training and/or certification for technologists and interpreters, are suggested.

What analytic method should clinicians use to derive spine T-scores and predict incident fractures in men? Results from the MrOS study.

UNLABELLED: In this study, the area under the curve was highest when using the lowest vertebral body T-score to diagnose osteoporosis. In men for whom hip imaging is not possible, the lowest vertebral body T-score improves the ability to diagnose osteoporosis in men who are likely to have an incident fragility fracture. INTRODUCTION: Spine T-scores have limited ability to predict fragility fracture. We hypothesized that using lowest vertebral body T-score to diagnose osteoporosis would better predict fracture. METHODS: Among men enrolled in the Osteoporotic Fractures in Men Study, we identified cases with incident clinical fracture (n = 484) and controls without fracture (n = 1,516). We analyzed the lumbar spine bone mineral density (BMD) in cases and controls (n = 2,000) to record the L1-L4 (referent), the lowest vertebral body, and International Society for Clinical Densitometry (ISCD)-determined T-scores using a male normative database and the L1-L4 T-score using a female normative database. We compared the ability of method to diagnose osteoporosis and, therefore, to predict incident clinical fragility fracture, using area under the receiver operator curves (AUCs) and the net reclassification index (NCI) as measures of diagnostic accuracy. ISCD-determined T-scores were determined in only 60 % of participants (n = 1,205). RESULTS: Among 1,205 men, the AUC to predict incident clinical fracture was 0.546 for L1-L4 male, 0.542 for the L1-L4 female, 0.585 for lowest vertebral body, and 0.559 for ISCD-determined T-score. The lowest vertebral body AUC was the only method significantly different from the referent method (p = 0.002). Likewise, a diagnosis of osteoporosis based on the lowest vertebral body T-score demonstrated a significantly better net reclassification index (NRI) than the referent method (net NRI +0.077, p = 0.005). By contrast, the net NRI for other methods of analysis did not differ from the referent method. CONCLUSION: Our study suggests that in men, the lowest vertebral body T-score is an acceptable method by which to estimate fracture risk.

Fasting and postprandial spot urine calcium-to-creatinine ratios do not detect hypercalciuria.

SUMMARY: Clinicians can diagnose high urine calcium by asking patients to collect urine for 24 h or to provide a random urine specimen. In this study, random urine calcium levels were not as accurate as those from the 24-h collection. Clinicians should only use 24-h collections to diagnose high urine calcium. INTRODUCTION: Clinicians diagnose hypercalciuria using a 24-h urine calcium (24HUC) or a spot urine-calcium-to-creatinine ratio (SUCCR) specimen. The SUCCR is reportedly interchangeable with the 24HUC. However, studies to date show mixed results when comparing SUCCR and 24HUC values. We systematically compared fasting and postprandial SUCCR measurements to 24HUC measurements using Bland-Altman analysis. METHODS: Twenty-one postmenopausal women aged 58 ± 7 years came to the research ward for three 24-h inpatient stays. At each study visit, research nurses collected fasting morning (n = 62) and postprandial (n = 62) spot urine specimens along with carefully timed and complete 24-h urine specimens (n = 63) from each woman. RESULTS: Hypercalciuria was present in 13 24HUC samples (21%) using an upper limit of 250 mg/24-h. The fasting SUCCR underestimated the 24HUC (Bland-Altman bias -71 mg/24-h), with a sensitivity and specificity for diagnosing hypercalciuria of 0% and 98%, respectively. The postprandial SUCCR overestimated the 24HUC (Bland-Altman bias +61 mg/24-h), with a sensitivity and specificity of 77% and 61%, respectively. The average of fasting and postprandial SUCCR measurements had a lower Bland-Altman bias of -3 mg/24-h but demonstrated a sensitivity and specificity of only 42% and 78%, respectively. CONCLUSIONS: The SUCCR is not interchangeable with the 24HUC. The fasting SUCCR systematically underestimates, and the postprandial SUCCR systematically overestimates, 24HUC. The average SUCCR demonstrates low sensitivity and specificity for hypercalciuria. Clinicians must use the 24HUC to diagnose hypercalciuria in postmenopausal women.

Vitamin D and calcium levels in Ugandan adults with human immunodeficiency virus and tuberculosis.

BACKGROUND: Vitamin D increases cathelicidin production, and might alter mortality due to tuberculosis (TB) in human immunodeficiency virus (HIV) coinfection. However, due to abundant sun exposure, vita min D levels might be excellent among Ugandans with HIV and TB. METHODS: We measured 25(OH)D and calcium levels in 50 HIV-negative, 50 HIV-infected and 50 TB-HIV coinfected Ugandan adults. RESULTS: Mean ± standard deviation 25(OH)D levels were 26 ± 7 ng/ml in HIV-negative, 28 ± 11 ng/ml in HIV-infected and 24 ± 11 ng/ml in TB-HIV co-infected adults (P > 0.05 all comparisons). Vitamin D deficiency (< 12 ng/ml) was present in 10% of the HIV-infected subjects, 12% of the TB-HIV co-infected and none of the healthy controls (P = 0.03 for healthy vs. TB, P > 0.05 for other comparisons); 20% of the healthy controls, 22% of the HIV-positive and 38% of the TB-HIV co-infected subjects (P = 0.047 for healthy vs. TB, P > 0.05 for other comparisons) had suboptimal vitamin D levels (< 20 ng/ml). No participant had hypercalcemia. Serum 25(OH)D levels correlated positively with body mass index (r = 0.22, P = 0.03) and serum calcium levels (r = 0.18, P = 0.03). CONCLUSIONS: Ugandan HIV-infected adults with and without TB commonly had suboptimal vitamin D levels. Clinical trials are needed to evaluate the effect of vitamin D on health outcomes in HIV-infected patients with low vitamin D levels.

Adjustment for body mass index and calcitrophic hormone levels improves the diagnostic accuracy of the spot urine calcium-to-creatinine ratio.

SUMMARY: Providers diagnose hypercalciuria using a 24-hour or random urine samples. We compared calcium measurements from paired 24-hour and morning urine samples; measurements correlated poorly. We developed a formula to correct random urine calcium levels. Corrected levels showed excellent agreement with 24-hour measurements. Until validation, providers should diagnose hypercalciuria using 24-hour tests. INTRODUCTION: Hypercalciuria is a risk factor for osteoporosis and nephrolithiasis. The 24-hour urine calcium (24HUC) measurement is the gold standard to diagnose hypercalciuria, but the spot urine calcium-to-creatinine ratio (SUCCR) is more convenient. Although authors claim they are interchangeable, we observed inconsistencies during the conduct of a clinical trial. Therefore, we systematically evaluated agreement between the tests. METHODS: During a 28-inpatient calcium absorption studies in 16 postmenopausal women, we simultaneously collected paired fasting morning and 24-hour urine specimens. RESULTS: We found moderate correlation between paired SUCCR and 24HUC specimens (r = 0.57, p = 0.002), but the SUCCR underestimated 24HUC by a mean of 83 mg (Bland-Altman). We diagnosed hypercalciuria (24HUC >250 mg) in eight specimens using the 24HUC, but only in two specimens using the SUCCR (25% sensitivity). We developed a regression model to predict 24HUC using SUCCR, parathyroid hormone, body mass index, and 1,25(OH)(2)D. The model improved diagnostic sensitivity to 100% and decreased Bland-Altman bias of the SUCCR to +0.06 mg/kg/24-hour. CONCLUSIONS: We conclude that the SUCCR underestimates urine calcium loss and does not reliably diagnose hypercalciuria. A formula derived from multivariate regression incorporating other readily measurable variables greatly improved the SUCCR's accuracy. Future studies must verify this correction before clinical implementation.

Adherence to alendronate in male veterans.

UNLABELLED: In one Veterans Affairs' medical center, alendronate non-adherence was more likely in male veterans who smoke or report side effects, and less likely in men undergoing bone densitometry during therapy. Providers urgently need programs to increase adherence to osteoporosis medications. Initial programs should target patients with risk factors for non-adherence. INTRODUCTION: Adherence to osteoporosis therapy in men is unknown. We hypothesized that ca. 50% of men at one center would be adherent to alendronate and one or more patient-specific factors would associate with adherence. METHODS: We conducted a retrospective chart review study of male veterans to determine the rates and predictors of alendronate adherence over two years. We excluded women, men who received primary care elsewhere and those who took alendronate for indications other than low bone mass. We defined adherence as a medication possession ratio > or =80% in the first 24 months of therapy. RESULTS: Adherence in the first 12 and 24 months of therapy was 59% and 54%, respectively. In multivariate analyses, non-adherence was more likely in men using tobacco (OR 2.08, 95% CI 1.13, 3.84, p = 0.02) and reporting side effects (OR 2.06, 95% CI 1.14, 3.73, p = 0.02) and less likely in men undergoing bone density during therapy (OR 0.49, 95% CI 0.26, 0.90, p = 0.02). CONCLUSIONS: Alendronate non-adherence is more likely in male veterans who smoke or report side effects, and less likely in men having bone densitometry during therapy. Providers urgently need programs to increase adherence to osteoporosis medications. Initial programs should target patients with risk factors for non-adherence.

Patient variables impact lumbar spine dual energy X-ray absorptiometry precision.

INTRODUCTION: Changes in bone mineral density are used to monitor osteoporosis therapy. To determine whether a change in bone mass is clinically significant, the precision of bone mineral density measurements must be known. METHODS: We therefore measured the impact of vertebral body exclusion on dual energy X-ray absorptiometry (DXA) precision. At one university and one Veterans Affairs DXA center, three radiology technologists each scanned 30 participants twice, with repositioning between scans, to estimate DXA precision. Three International Society for Clinical Densitometry-certified physicians reviewed all lumbar spinal scans to note the presence of focal structural defects. We calculated precision for subsets of vertebrae, and for virtual samples of patients with and without physician-identified vertebral focal structural defects. We graphed the reciprocal of least significant change versus bone area to determine the dependence of precision on interpreted scan area. RESULTS: Within each sample, greater interpretable bone area improved precision. The contribution of interpreted bone area to precision differed among the samples, ranging from 57 to 94%. Greater population bone mineral density heterogeneity and presence of focal structural defects each decreased precision. CONCLUSION: All bone densitometry centers must determine precision using a sample representative of their served populations. Failure to do so may lead to incorrect determination of least significant change. Population heterogeneity, vertebral body exclusion and presence of focal structural defects each decreases precision.

Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization.

Endemic hypovitaminosis D contributes to osteoporosis development. However, variation in 25-hydroxyvitamin D (25OHD) measurement is reported and confounds the diagnosis of vitamin D insufficiency/deficiency. This report emphasizes the marked variability observed in serum 25OHD measurements between laboratories.Initially, postmenopausal women had serum 25OHD determinations: 42 in laboratory A, 20 in laboratory B. Their mean (sem) serum 25OHD concentrations were 46 (2.1) and 21 (2.3) ng/ml in laboratories A and B, respectively. Furthermore, there was little overlap in serum 25OHD among these clinically similar individuals. Specifically, 17% of those measured in laboratory A but 90% in laboratory B were below an arbitrary threshold value of 32 ng/ml.Subsequently, serum was obtained from 10 healthy adults. Two aliquots from each individual, one of which was spiked with 20 ng/ml 25OHD, were sent to six laboratories. Substantial variability was noted between these six laboratories. The mean serum 25OHD concentration ranged from 17.1-35.6 ng/ml. Similarly, the mean increase produced by spiking with 20 ng/ml ranged from 7.7-18.0 ng/ml.In conclusion, 25OHD assays yield markedly differing results; whether an individual is found to have low or normal vitamin D status is a function of the laboratory used. If the medical community is to make progress in correcting widespread hypovitaminosis D, 25OHD measurement must be standardized.

The safety and efficacy of leflunomide in combination with infliximab in rheumatoid arthritis.

OBJECTIVE: To report the safety and efficacy of leflunomide (LEF) in combination with infliximab (INF) for the treatment of rheumatoid arthritis. METHODS: In an open, multicenter, retrospective study, data were collected on the safety and efficacy of LEF and INF. RESULTS: Eighty-eight patients received the combination of LEF and INF for an average of 6.6 months and a total exposure of 581 patient-months. The mean duration of LEF was 17 +/- 9 months (range 3-32 months; median 18.5 months) with an average of 4.8 INF infusions per patient. In all but 3 subjects, LEF was used initially and INF was added later. Infusion reactions occurred in 3 patients (0.7% of all infusions). A total of 34% of subjects experienced adverse events and in 6 (6.8% of the group) these were deemed serious. Ten infections occurred when patients were taking the combination; 9 patients recovered fully and 1 died of bacterial pneumonia. A lifetime smoker developed lung cancer and another patient was found to have colon cancer. CONCLUSIONS: The adverse events noted within the combination therapy group were in keeping with the known risks of each drug when used individually. Limited data were available on efficacy, but a general improvement in disease control was noted with the combination of drugs, which for most patients involved the addition of INF to previous use of LEF.

Risk factors associated with thrombosis in patients with antiphospholipid antibodies.

OBJECTIVE: To define risk factors associated with thrombosis in patients with antiphospholipid antibodies (aPL). METHODS: Ninety-nine patients with aPL, most of whom had prior thrombosis, were evaluated for the presence of acquired and inherited thrombophilic states. Genomic testing was performed for factor V(R506Q), 3' prothrombin (PTG) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms. Clinical records were reviewed for the presence of acquired risk factors (RF) for thrombosis and events associated with aPL. Univariate statistical analysis was performed using Fisher's exact testing. A neural network statistical model was also used to identify which thrombophilic risk factors were most important in development of arterial and venous thrombosis. RESULTS: For arterial thrombosis, hypertension, tobacco use, hyperlipidemia, and diabetes mellitus were the most important predictors of thrombosis. By contrast, tobacco use, the 3' PTG and factor V(R506Q) polymorphisms, and previous cardiac surgery were the most important predictors of venous thrombosis. CONCLUSION: In this hypothesis-generating retrospective study, acquired risk factors were most important in arterial thrombosis, while the presence of factor V(R506Q) and 3' PTG polymorphisms were more important in the development of venous thrombosis. These findings are being validated in an ongoing, prospective study.

High affinity interaction of yeast transcriptional regulator, Mot1, with TATA box-binding protein (TBP).

Yeast Mot1, an essential ATP-dependent regulator of basal transcription, removes TATA box-binding protein (TBP) from TATA sites in vitro. Complexes of Mot1 and Spt15 (yeast TBP), radiolabeled in vitro, were immunoprecipitated with anti-TBP (or anti-Mot1) antibodies in the absence of DNA, showing Mot1 binds TBP in solution. Mot1 N-terminal deletions (residues 25-801) abolished TBP binding, whereas C-terminal ATPase domain deletions (residues 802-1867) did not. Complex formation was prevented above 200 mm salt, consistent with electrostatic interaction. Correspondingly, TBP variants lacking solvent-exposed positive charge did not bind Mot1, whereas a mutant lacking positive charge within the DNA-binding groove bound Mot1. ATPase-defective mutant, Mot1(D1408N), which inhibits growth when overexpressed (but is suppressed by co-overexpression of TBP), bound TBP normally in vitro, suggesting it forms nonrecyclable complexes. N-terminal deletions of Mot1(D1408N) were not growth-inhibitory. C-terminal deletions were toxic when overexpressed, and toxicity was ameliorated by TBP co-overproduction. Residues 1-800 of Mot1 are therefore necessary and sufficient for TBP binding. The N terminus of 89B, a tissue-specific Drosophila Mot1 homolog, bound the TBP-like factor, dTRF1. Native Mot1 and derivatives deleterious to growth localized in the nucleus, whereas nontoxic derivatives localized to the cytosol, suggesting TBP binding and nuclear transport of Mot1 are coupled.

Experiences from the Danish programme for eradication of bovine virus diarrhoea (BVD) 1994-1998 with special reference to legislation and causes of infection.

The main experiences from the Danish bovine virus diarrhoea (BVD) eradication programme over 5 years from 1994 to 1999 are presented. The last 3 years of the programme has been strongly supported by legislation. The most important regulations have been blood testing of live animals before movement to other herds, common pastures or exhibitions, and monitoring of all herds at regular intervals for the presence of the infection. Nevertheless, free herds have experienced infection, e.g., 204 dairy herds in 1998. Of herds found to be infected in the period from July 1997 through June 1998 after previously having been registered to be BVD-free, 67 herds were thoroughly investigated. Nineteen herds (28%) were found infected because of purchase of pregnant cows or heifers which delivered persistently infected (PI) calves, and 24 (36%) and two (3%) because of PI animals on neighbouring pastures or in neighbouring farm houses, respectively. In five herds (7%) pregnant heifers had become infected on one and the same common pasture, while in 17 herds (25%) no immediate cause of infection could be demonstrated. Yet, airborne spread from PI herds as a source of infection was suspected in some of these cases. It was furthermore concluded from investigations presented, that antibody-positive AI bulls were a remote but unlikely possibility. Free-living deer in Denmark had to be considered uninfected. Presence of PI-animals in sheep on infected farms has been seen and is paid attention to in individual cases. The results underline the need for legislation to be used in eradication programmes in areas with a high prevalence of infection and to be introduced right from the beginning in order to minimise the risk of infection for free herds.

Purification and enzymic properties of Mot1 ATPase, a regulator of basal transcription in the yeast Saccharomyces cerevisiae.

The 1867-residue Mot1 protein is a member of a superfamily of ATPases, some of which are helicases, that interact with protein-nucleic acid assemblies. Mot1 is an essential regulator of RNA polymerase II-dependent transcription in vivo and dissociates TATA box-binding protein (TBP)-DNA complexes in vitro. Mot1-(His)(6) was purified to apparent homogeneity from yeast extracts. The preparation efficiently dissociated TBP.TATA complexes, suggesting that no other protein or cofactor is required. Mot1 behaved as a non-globular monomer in hydrodynamic studies, and no association was detected between differentially tagged co-expressed Mot1 constructs. ATPase activity was stimulated about 10-fold by high ionic strength or alkaline pH, or by deletion of the N-terminal TBP-binding segment, suggesting that the N-terminal domain negatively regulates the C-terminal ATPase domain (Mot1C). Correspondingly, at moderate salt concentration, Mot1 ATPase (but not Mot1C) was stimulated >/=10-fold by yeast TBP, suggesting that interaction with TBP relieves a conformational constraint in Mot1. Double- or single-stranded TATA-containing DNA did not affect ATPase activity of Mot1 or Mot1C, with or without TBP. Mot1 did not exhibit detectable helicase activity in strand displacement assays using substrates with flush ends or 5'- or 3'-overhangs. Mot1-catalyzed dissociation of TBP from DNA was not prevented by a psoralen cross-link positioned immediately preceding the TATA sequence. Thus, Mot1 most likely promotes release of TBP from TATA-containing DNA by causing a structural change in TBP itself, rather than by strand unwinding.

Autoantibodies and common viral illnesses.

OBJECTIVES: To review the literature about common autoantibodies produced in association with viral infection. METHODS: Medline review of the medical literature published in English. RESULTS: Common viral infections are often associated with low-titer, polyspecific autoantibodies. However, high-titer antinuclear antibodies, double-stranded DNA antibodies, anticardiolipin antibodies, and other subtype antibodies may be found. Hepatitis C and B virus, human immunodeficiency virus, and parvovirus B19 appear to be associated with autoantibodies more commonly than other viruses. CONCLUSIONS: Transient autoantibodies resulting from viral infections are not uncommon. Clinical and laboratory follow-up over time will help distinguish between connective tissue disease and self-limited illness.