Impact of dynamic contrast-enhanced MRI in 1.5 T versus 3 T MRI for clinically significant prostate cancer detection.

PURPOSE: This study analyzes the value of dynamic contrast-enhanced MRI (DCE) of the prostate on 1.5 T and 3 T examinations in patients within PI-RADS category 4. METHODS: In this retrospective, bi-centric, cohort study all consecutive patients classified as PI-RADS 4 in mpMRI with 100 verified prostate cancers (PCa) in subsequent MRI/US-guided fusion biopsy were included for 1.5 T and 3 T, each. PCa detection in index lesions (IL) upgraded to PI-RADS 4 based on positive DCE findings was compared between 1.5 T and 3 T. Secondary objectives are subgroup analysis of PZ lesions and comparison of ISUP grade group distribution between 1.5 T and 3 T. RESULTS: In total, 293 patients within PI-RADS category 4, including 152 (mean 66 ± 8y; median PSA 6.4 ng/ml;116 PZ IL) in the 1.5 T group and 141 (mean 65 ± 8y; median PSA 7.2 ng/ml;100 PZ IL) in the 3 T group were included. Overall amount of PCa (66 % vs 71 %; p = 0.346) and portion of upgraded IL (28 % vs 21 %; p = 0.126) did not differ significantly. At 1.5 T PCa detection was higher in upgraded PZ lesions compared to 3 T (23 % vs 14 %; p = 0.048). The amount of upgraded PZ lesions with ISUP grade group 2-5 PCa was significantly higher at 1.5 T versus 3 T (13.8 % vs 4.0 %; p = 0.007). 33 % (11/33; 1.5 T) and 32 % (10/31; 3 T) of the ISUP grade group 1 PCa of the PZ lesions were detected in upgraded lesions (10% of all PZ index lesions, respectively). CONCLUSION: DCE enabled the detection of a substantial amount of additional clinically significant PCa in prostate mpMRI at 1.5 T. The effect was smaller at 3 T and was accompanied in relation to 1.5 T by higher risk of overdiagnosis due to detection of additional low-risk PCa.

Cognitive aging on latent constructs for visual processing capacity: a novel structural equation modeling framework with causal assumptions based on a theory of visual attention.

We examined the effects of normal aging on visual cognition in a sample of 112 healthy adults aged 60-75. A testbattery was designed to capture high-level measures of visual working memory and low-level measures of visuospatial attention and memory. To answer questions of how cognitive aging affects specific aspects of visual processing capacity, we used confirmatory factor analyses in Structural Equation Modeling (SEM; Model 2), informed by functional structures that were modeled with path analyses in SEM (Model 1). The results show that aging effects were selective to measures of visual processing speed compared to visual short-term memory (VSTM) capacity (Model 2). These results are consistent with some studies reporting selective aging effects on processing speed, and inconsistent with other studies reporting aging effects on both processing speed and VSTM capacity. In the discussion we argue that this discrepancy may be mediated by differences in age ranges, and variables of demography. The study demonstrates that SEM is a sensitive method to detect cognitive aging effects even within a narrow age-range, and a useful approach to structure the relationships between measured variables, and the cognitive functional foundation they supposedly represent.

Osteoporosis quality indicators using healthcare utilization data.

SUMMARY: Healthcare utilization data may be used to examine the quality of osteoporosis management by identifying dual-energy X-ray absorptiometry (DXA) testing (sensitivity = 98%, specificity = 93%) and osteoporosis pharmacotherapy (κ = 0.81) with minimal measurement error. INTRODUCTION: In osteoporosis, key quality indicators among older women include risk assessment by DXA and/or pharmacotherapy within 6 months following fracture. METHODS: The purpose of this study was to examine healthcare utilization data for use as quality indicators of osteoporosis management. We linked data from 858 community-dwelling women aged over 65 years who completed a standardized telephone interview about osteoporosis management to their healthcare utilization (medical and pharmacy claims) data. Agreement between self-report of osteoporosis pharmacotherapy and pharmacy claims was examined using kappa statistics. We examined the sensitivity and specificity of medical claims to identify DXA testing as well as the sensitivity and specificity of medical and pharmacy claims to identify those with DXA-documented osteoporosis (T-score ≤ -2.5). RESULTS: Participants were aged 75 (SD = 6) years on average; 96% were Caucasian. Agreement between self-report and claims-based osteoporosis pharmacotherapy was very good (κ = 0.81; 95% CI = 0.76, 0.86). The sensitivity of medical claims to identify DXA testing was 98% (95% CI = 95.9, 99.1), with estimated specificity of 93% (95% CI = 89.8, 95.4). We abstracted DXA results from test reports of 359 women, of whom 114 (32%) were identified with osteoporosis. Medical (osteoporosis diagnosis) and pharmacy (osteoporosis pharmacotherapy) claims within a year after DXA testing had a sensitivity of 80% (95% CI = 71.3, 86.8) and specificity of 72% (95% CI = 66.2, 77.8) to identify DXA-documented osteoporosis. CONCLUSION: Healthcare utilization data may be used to examine the quality of osteoporosis management by identifying DXA testing and osteoporosis pharmacotherapy (care processes) with minimal measurement error. However, medical and pharmacy claims alone do not provide a good means for identifying women with underlying osteoporosis.

Subclinical hypothyroidism affects mitochondrial function.

The aim of the present study was to examine mitochondrial function in cells from persons with subclinical hypothyroidism and euthyroid controls. The participating persons were examined clinically and had basal oxygen consumption (VO(2)) determined. The concentrations of thyroid hormones and thyrotropine stimulating hormone were determined, and mitochondrial function in isolated mononuclear blood cells was examined by enzymatic methods [citrate synthase activity (CS)] and by flow cytometry (mitochondrial membrane potential by TMRM fluorescence and mitochondrial mass by MTG fluorescence). The ratio of T(4)/T(3) was lowered in subclinical hypothyroidism patients compared to controls (2.5+/-0.5 vs. 2.9+/-0.4, p=0.005). VO(2) was increased in persons with subclinical hypothyroidism compared to controls (adolescents: 134+/-27 ml O(2)/min*m(2) vs. 119+/-27 ml O(2)/min*m(2), p=0.006, adults: 139+/-14 ml O(2)/min*m(2) vs. 121+/-17 ml O(2)/min*m(2), p=0.001). The mitochondrial function, represented by citrate synthase activity, MTG, and TMRM fluorescence were all increased (CS in subclinical hypothyroidism vs. controls: 0.074+/-0.044 nmol/mg*min vs. 0.056+/-0.021 nmol/mg*min, p=0.005; MTG fluorescence in subclinical hypothyroidism vs. controls: 7,482+/-1,733 a.u. vs. 6,391+/-2,171 a.u., p=0.027; TMRM fluorescence in subclinical hypothyroidism vs. controls: 13,449+/-3,807 a.u. vs. 11,733+/-4,473 a.u, p=0.04). Our results indicate an increased mitochondrial stimulation, eventually caused by increased deiodination of T(4) to intracellular bioactive iodothyronines in adults and adolescents with subclinical hypothyroidism.

Measure of expression of mitochondrial related genes in human mononuclear blood cells, adipose white tissue and smooth muscle cells.

BACKGROUND: The role of mitochondrial dysfunction is currently studied intensively, but the cumbersome procedure of obtaining tissue from humans has restricted the number of subjects studied. Therefore, the aim of the present study was to examine the expression of mitochondrial related genes in blood cells from humans and to compare the results with measurements of mitochondrial membrane potential known to be regulated by thyroid hormones. METHODS: In a group of 17 healthy women subscribed for hysterectomy on a benign basis, muscle tissue, fat tissue samples and blood specimens were obtained. Mitochondrial mass and membrane potential was examined in peripheral blood monocytes by flow cytometry. Gene expression of PGC-1alpha, PGC-1beta, NFR-1, NRF-2 and TFAM was determined by real-time PCR. RESULTS: All genes were expressed in the 3 tissues examined, though with different magnitude. Most genes were expressed in mononuclear blood cells at a magnitude comparable to that in white adipose tissue. Furthermore, a significant correlation was observed between PGC-1beta and Mitochondrial Membrane Potential (MMP) and Mitochondrial Mass (MM). CONCLUSION: Measurement of expression of mitochondrial related genes in human mononuclear blood cells may be useful for examining mitochondrial function and regulation by thyroid hormones in humans.

Evidence of mitochondrial dysfunction in obese adolescents.

AIM: Although obesity and weight gain generally are anticipated to be caused by an imbalance between energy intake and energy expenditure, the significance of thyroid hormones (TH) remains unclear. Examination of mitochondrial function may reflect intracellular thyroid hormone effect and elucidate whether a lower metabolic rate is present. METHODS: In a group of 34 obese adolescents (age <16 years and body mass index above the age-related 95th percentile), and an age- and gender-matched group of 32 lean adolescent, thyroid stimulating hormone (TSH) and basal oxygen consumption were measured and mitochondrial function in peripheral blood monocytes was determined by flow cytometry. RESULTS: Significant increase in TSH (3.06 +/- 1.56 mU/L vs. 2.33 +/- 0.91 mU/L, p < 0.05) and a decrease in VO2 (129 +/- 16 mL O2/m(2)*min vs. 146 +/- 15 mL O2/m(2)*min, p < 0.05) were observed in obese adolescents compared with lean adolescents. Flow cytometry analysis demonstrated a lower mitochondrial mass (6385 +/- 1962 a.u. vs. 7608 +/- 2328 a.u., p < 0.05) and mitochondrial membrane potential (11426 +/- 3861 a.u. vs. 14017 +/- 5536 a.u., p < 0.05) in obese adolescents compared with lean adolescents. These results are even more pronounced in adolescents with obese mothers. CONCLUSION: In obese adolescents, the increased TSH and lowered VO2 propose a lowered basal metabolic rate and the impaired mitochondrial function suggests a decreased thyroid hormone stimulation of mitochondrial energy production. The maternal in-heritage is suggestive of a basal metabolic defect or mitochondrial resistance for TH.

Overall and meal-specific macronutrient intake in Belgian primary school children.

In the fall of 1991, dietary intake of 1,321 primary school children aged 6-12 years was studied in 79 schools in an area called 'South Campine' in Flanders-the Dutch-speaking part of Belgium. Assessment of dietary intake was done using the '24-hour estimated food record method'. The energy distribution over the macronutrients showed no significant difference between boys and girls. On average 37.2% (SD 7.88%) of energy came from total fat and 15.4% (SD 3.70%) from saturated fatty acids; 49.0% (SD 7.87%) from total carbohydrates with 21.8% (SD 5.84%) from complex carbohydrates and 27.7% (SD 7.79%) from free sugars. Snacks accounted for on average 19.5% (SD 10.83%) of total energy intake; on average 55.7% (SD 21.22%) of the energy in these snacks was represented by free sugars. Lunch and dinner had very high fat contents (around 40% of energy). Already at this young age, the dietary pattern is deviating strongly from the recommended population nutrient goals.

Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis.

OBJECTIVE: To determine if first-trimester exposure to sex hormones, and oral contraceptives (OCs) specifically, is associated with an increased risk of external fetal genital malformations. DATA SOURCES: MEDLINE and Science Citation Index data bases were searched for the years 1966-1992 for relevant English-language articles on first-trimester sex-hormone exposure and fetal genital changes. METHODS OF STUDY SELECTION: One hundred eighty-six articles were identified initially. Inclusion criteria were cohort or case-control studies, first-trimester sex-hormone exposure, and live infants or full-term stillborn infants with external genital malformations. Exclusion criteria were diethylstilbestrol exposure, spontaneous abortions, and teratogen exposure. DATA EXTRACTION AND SYNTHESIS: The Methods section of each study was reviewed independently by two authors and two outside reviewers, using the above criteria. Fourteen studies, seven cohort and seven case-control, involving 65,567 women, met the criteria for meta-analysis. Extracted data were entered into 2 x 2 tables. The overall summary odds ratio (OR) was 1.09 (95% confidence interval [CI] 0.90-1.32); subanalysis of OC exposure identified an OR of 0.98 (95% CI 0.24-3.94). CONCLUSION: There was no association between first-trimester exposure to sex hormones generally (or to OCs specifically) and external genital malformations. Thus, women exposed to sex hormones after conception may be assured there is no increased risk of fetal sexual malformation.