Radiologists' Diagnostic Performance in Differentiation of Rickets and Classic Metaphyseal Lesions on Radiographs: A Multicenter Study.

BACKGROUND. Despite evidence supporting the specificity of classic metaphyseal lesions (CML) for the diagnosis of child abuse, some medicolegal practitioners claim that CML result from rickets rather than trauma. OBJECTIVE. The purpose of this study was to evaluate radiologists' diagnostic performance in differentiating rickets and CML on radiographs. METHODS. This retrospective seven-center study included children younger than 2 years who underwent knee radiography from January 2007 to December 2018 and who had either rickets (25-hydroxyvitamin D level < 20 ng/mL and abnormal knee radiographs) or knee CML and a diagnosis of child abuse from a child abuse pediatrician. Additional injuries were identified through medical record review. Radiographs were cropped and zoomed to present similar depictions of the knee. Eight radiologists independently interpreted radiographs for diagnoses of rickets or CML, rated confidence levels, and recorded associated radiographic signs. RESULTS. Seventy children (27 girls, 43 boys) had rickets; 77 children (37 girls, 40 boys) had CML. Children with CML were younger than those with rickets (mean, 3.7 vs 14.2 months, p < .001; 89.6% vs 5.7% younger than 6 months; 3.9% vs 65.7% older than 1 year). All children with CML had injuries in addition to the knee CML identified at physical examination or other imaging examinations. Radiologists had almost perfect agreement for moderate- or high-confidence interpretations of rickets (κ = 0.92) and CML (κ = 0.89). Across radiologists, estimated sensitivity, specificity, and accuracy for CML for moderate- or high-confidence interpretations were 95.1%, 97.0%, and 96.0%. Accuracy was not significantly different between pediatric and nonpediatric radiologists (p = .20) or between less experienced and more experienced radiologists (p = .57). Loss of metaphyseal zone of provisional calcification, cupping, fraying, and physeal widening were more common in rickets than CML, being detected in less than 4% of children with CML. Corner fracture, bucket-handle fracture, subphyseal lucency, deformed corner, metaphyseal irregularity, and subperiosteal new bone formation were more common in CML than rickets, being detected in less than 4% of children with rickets. CONCLUSION. Radiologists had high interobserver agreement and high diagnostic performance for differentiating rickets and CML. Recognition that CML mostly occur in children younger than 6 months and are unusual in children older than 1 year may assist interpretation. CLINICAL IMPACT. Rickets and CML have distinct radiographic signs, and radiologists can reliably differentiate these two entities.

Liat1, an arginyltransferase-binding protein whose evolution among primates involved changes in the numbers of its 10-residue repeats.

The arginyltransferase Ate1 is a component of the N-end rule pathway, which recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. At least six isoforms of mouse Ate1 are produced through alternative splicing of Ate1 pre-mRNA. We identified a previously uncharacterized mouse protein, termed Liat1 (ligand of Ate1), that interacts with Ate1 but does not appear to be its arginylation substrate. Liat1 has a higher affinity for the isoforms Ate1(1A7A) and Ate1(1B7A). Liat1 stimulated the in vitro N-terminal arginylation of a model substrate by Ate1. All examined vertebrate and some invertebrate genomes encode proteins sequelogous (similar in sequence) to mouse Liat1. Sequelogs of Liat1 share a highly conserved ∼30-residue region that is shown here to be required for the binding of Liat1 to Ate1. We also identified non-Ate1 proteins that interact with Liat1. In contrast to Liat1 genes of nonprimate mammals, Liat1 genes of primates are subtelomeric, a location that tends to confer evolutionary instability on a gene. Remarkably, Liat1 proteins of some primates, from macaques to humans, contain tandem repeats of a 10-residue sequence, whereas Liat1 proteins of other mammals contain a single copy of this motif. Quantities of these repeats are, in general, different in Liat1 of different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in the gibbon, gorilla, orangutan, bonobo, neanderthal, and human Liat1, respectively, suggesting that repeat number changes in this previously uncharacterized protein may contribute to evolution of primates.

Exploring the full range of N⋯I⋯X halogen-bonding interactions within a single compound using pressure.

The response of the trimethylammonium-iodinechloride and diiodide (TMA-ICl/I2) crystal structures have been examined under high pressure using neutron powder diffraction. TMA-ICl exhibits impressive pressure-driven electronic flexibility, where the N⋯I-Cl interactions progressively encompass all the distances represented in analogous structures recorded in the Cambridge Structural Database. Comparison with the TMA-I2 complex reveals that this flexibility is owed to the electronegativity of the chlorine atom which induces increased distortion of the iodine electron cloud. This structural flexibility may be influential in the future design of functional molecular materials.

COVID-19 Diagnosis on Chest Radiograph Using Artificial Intelligence.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted the world since 2019, causing significant morbidity and mortality in developed and developing countries alike. Although substantial resources have been diverted to developing diagnostic, preventative, and treatment measures, disparities in the availability and efficacy of these tools vary across countries. We seek to assess the ability of commercial artificial intelligence (AI) technology to diagnose COVID-19 by analyzing chest radiographs. MATERIALS AND METHODS: Chest radiographs taken from symptomatic patients within two days of polymerase chain reaction (PCR) tests were assessed for COVID-19 infection by board-certified radiologists and commercially available AI software. Sixty patients with negative and 60 with positive COVID reverse transcription-polymerase chain reaction (RT-PCR) tests were chosen. Results were compared against results of the PCR test for accuracy and statistically analyzed by receiver operating characteristic (ROC) curves along with area under the curve (AUC) values. RESULTS: A total of 120 chest radiographs (60 positive and 60 negative RT-PCR tests) radiographs were analyzed. The AI software performed significantly better than chance (p = 0.001) and did not differ significantly from the radiologist ROC curve (p = 0.78). CONCLUSION: Commercially available AI software was not inferior compared with trained radiologists in accurately identifying COVID-19 cases by analyzing radiographs. While RT-PCR testing remains the standard, current advances in AI help correctly analyze chest radiographs to diagnose COVID-19 infection.

Hypoxic respiratory failure in acute appendicitis: A bronchoperitoneal fistula as the presenting symptom of appendicitis in the setting of pediatric COVID-19.

Symptomatic COVID-19 less frequently affects the pediatric population and is often associated with atypical presenting symptoms. Here we describe a nine-year-old patient who presented with acute hypoxic respiratory failure and was found to have perforated appendicitis, intra-abdominal abscess, and bronchoperitoneal fistula. The rapid progression of this pathology, complex critical care decision making, and ultimate surgical management has not been previously described. Documenting this patient's clinical course and effective treatments may serve to inform and guide the medical community and pediatric care providers as the world continues to combat the COVID-19 pandemic.

Mouse Dfa is a repressor of TATA-box promoters and interacts with the Abt1 activator of basal transcription.

Our study of the mouse Ate1 arginyltransferase, a component of the N-end rule pathway, has shown that Ate1 pre-mRNA is produced from a bidirectional promoter that also expresses, in the opposite direction, a previously uncharacterized gene (Hu, R. G., Brower, C. S., Wang, H., Davydov, I. V., Sheng, J., Zhou, J., Kwon, Y. T., and Varshavsky, A. (2006) J. Biol. Chem. 281, 32559-32573). In this work, we began analyzing this gene, termed Dfa (divergent from Ate1). Mouse Dfa was found to be transcribed from both the bidirectional P(Ate1/Dfa) promoter and other nearby promoters. The resulting transcripts are alternatively spliced, yielding a complex set of Dfa mRNAs that are present largely, although not exclusively, in the testis. A specific Dfa mRNA encodes, via its 3'-terminal exon, a 217-residue protein termed Dfa(A). Other Dfa mRNAs also contain this exon. Dfa(A) is sequelogous (similar in sequence) to a region of the human/mouse HTEX4 protein, whose physiological function is unknown. We produced an affinity-purified antibody to recombinant mouse Dfa(A) that detected a 35-kDa protein in the mouse testis and in several cell lines. Experiments in which RNA interference was used to down-regulate Dfa indicated that the 35-kDa protein was indeed Dfa(A). Furthermore, Dfa(A) was present in the interchromatin granule clusters and was also found to bind to the Ggnbp1 gametogenetin-binding protein-1 and to the Abt1 activator of basal transcription that interacts with the TATA-binding protein. Given these results, RNA interference was used to probe the influence of Dfa levels in luciferase reporter assays. We found that Dfa(A) acts as a repressor of TATA-box transcriptional promoters.

Poor maternal nutrition leads to alterations in oxidative stress, antioxidant defense capacity, and markers of fibrosis in rat islets: potential underlying mechanisms for development of the diabetic phenotype in later life.

Low birth weight is associated with glucose intolerance, insulin resistance, and type 2 diabetes (T2D) in later life. Good evidence indicates that the environment plays an important role in this relationship. However, the mechanisms underlying these relationships are defined poorly. Islets are particularly susceptible to oxidative stress, and this condition combined with fibrosis is thought to be instrumental in T2D pathogenesis. Here we use our maternal low-protein (LP) rat model to determine the effect of early diet on oxidative stress and fibrosis in pancreatic islets of male offspring at 3 and 15 mo of age. Islet xanthine oxidase (XO) expression was increased in 15-mo LP offspring, which suggests increased oxidative-stress. Manganese superoxide-dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), and heme oxygenase-1 (HO-1) (antioxidant enzymes) were reduced significantly in LP offspring, which indicated impairment of oxidative defense. Expression of fibrosis markers collagen I and collagen III also increased in 15-mo LP offspring. Angiotensin II receptor type I (AT(II)R(1)), induced by hyperglycemia and oxidative-stress, was significantly up-regulated in 15-mo LP offspring. Lipid peroxidation was also increased in 15-mo LP animals. We conclude that maternal protein restriction causes age-associated increased oxidative stress, impairment of oxidative defense, and fibrosis. These findings provide mechanisms by which suboptimal early nutrition can lead to T2D development later in life.

Bayesian information criterion for longitudinal and clustered data.

When a number of models are fit to the same data set, one method of choosing the 'best' model is to select the model for which Akaike's information criterion (AIC) is lowest. AIC applies when maximum likelihood is used to estimate the unknown parameters in the model. The value of -2 log likelihood for each model fit is penalized by adding twice the number of estimated parameters. The number of estimated parameters includes both the linear parameters and parameters in the covariance structure. Another criterion for model selection is the Bayesian information criterion (BIC). BIC penalizes -2 log likelihood by adding the number of estimated parameters multiplied by the log of the sample size. For large sample sizes, BIC penalizes -2 log likelihood much more than AIC making it harder to enter new parameters into the model. An assumption in BIC is that the observations are independent. In mixed models, the observations are not independent. This paper develops a method for calculating the 'effective sample size' for mixed models based on Fisher's information. The effective sample size replaces the sample size in BIC and can vary from the number of subjects to the number of observations. A number of error models are considered based on a general mixed model including unstructured, compound symmetry.

Successful reduction of recalcitrant ileocolic intussusception with a double-balloon-tipped catheter that prevents air leaks and catheter expulsion.

Noninvasive reduction of ileocolic intussusception requires increasing intracolonic pressure via gas or liquid administered through a rectal catheter. A tight seal around the catheter is required to maintain intracolonic pressures and this tight seal is difficult to maintain with existing techniques. I describe the safe and effective use of a catheter with 2 balloons near the tip that surround the anus internally and externally to prevent leakage of air during an enema on a toddler after failure with a single-balloon tipped catheter.

Sharing specialist skills for diabetes in an inner city: a comparison of two primary care organisations over 4 years.

OBJECTIVE: To evaluate the effects of organizational change and sharing of specialist skills and information technology for diabetes in two primary care groups (PCGs) over 4 years. METHODS: In PCG-A, an intervention comprised dedicated specialist sessions in primary care, clinical guidelines, educational meetings for professionals and a shared diabetes electronic patient record (EPR). Comparison was made with the neighbouring PCG-B as control. In intervention and control PCGs, practice development work was undertaken for a new contract for family doctors. Data were collected for clinical measures, practice organizational characteristics and professional and patient views. RESULTS: Data were analysed for 26 general practices including 17 in PCG-A and nine in PCG-B. The median practice-specific proportions of patients with HbA1c recorded annually increased in both areas: PCG-A from median 65% to 77%, while PCG-B from 53% to 84%. For cholesterol recording, PCG-A increased from 50% to 76%, and PCG-B from 56% to 80%. Organizational changes in both PCGs included the establishment of recall systems, dedicated clinics and educational sessions for patients. In both PCGs, practices performing poorly at baseline showed the greatest improvements in organization and clinical practice. Primary care professionals' satisfaction with access and communication with diabetes specialist doctors and nurses increased, more so in the intervention PCG. Only 16% of primary care professional respondents used the diabetes EPR at least monthly. Patient satisfaction and knowledge did not change. CONCLUSIONS: Improvements in practices' organizational arrangements were associated with improvements in clinical care in both PCGs. Sharing specialist skills in one PCG was associated with increased professional satisfaction but no net improvement in clinical measures. A shared diabetes EPR is unlikely to be used, unless integrated with practice information systems.

Abinitio structure determination using dispersive differences from multiple-wavelength synchrotron-radiation powder diffraction data.

The purpose of this paper and a test case study is to assess a method of ab initio structure solution from powder diffraction data using f' difference techniques. A theoretical foundation for the approach used is first provided. Then, with a test case (nickel sulfate hexahydrate), it is shown that both the position of the anomalous scatterer (Ni) can be determined and the structure can be developed in full. Specifically, synchrotron-radiation data were collected at two wavelengths close to the K edge for Ni and three wavelengths remote from the Ni absorption edge, at 1.3, 1.8 and 2.16 A. These five wavelengths then allowed various combinations to be tried to establish which wavelength pairs gave the optimum signal in the Patterson maps using dispersive amplitude differences. The initial phases derived from the metal-atom position then allowed the structure to be fully developed by difference Fourier cycling. The relevance of these developments to structure-solution possibilities for proteins via powder dispersive difference data is then outlined.

Effect of thyroid hormone binding proteins on insulin receptor binding of B1-thyronine-insulin analogues.

Certain thyronine-insulin analogues, which form non-covalent complexes with plasma proteins, have been shown to act preferentially in the liver. We hypothesized that this property may be dependent on the ability of the analogue to bind to the insulin receptor without prior dissociation from the binding protein. NaB1-L-thyroxyl-insulin, NaB1-3,3',5'-triiodothyronine-insulin, NaB1-D-thyroxyl-insulin and NaB1-L-thyroxyl-aminolauroyl-insulin were compared with insulin for their capacity to inhibit the binding of [125I]TyrA14-insulin to rat liver plasma membrane in albumin-free buffer. Effective doses at 50% maximum inhibition of binding (ED50) were calculated with and without addition of the thyroid hormone binding proteins transthyretin, thyroxine binding globulin and human serum albumin. The binding of thyronine-insulin analogues to insulin receptors was inhibited in a dose-dependent manner by the addition of thyroid hormone binding proteins at concentrations in the physiological range. Complexes of thyronine-insulin analogues with thyroid hormone binding proteins exhibit impaired insulin receptor binding affinities compared with those of the analogues in their free form. Hepatoselectivity in vivo may not depend on binding of the intact complexes to hepatocytes. These results have implications for the physiological role of hormone binding proteins and the in vivo properties of other insulin analogues which bind to plasma proteins.

Insulin-like growth factor I has a direct effect on glucose and protein metabolism, but no effect on lipid metabolism in type 1 diabetes.

There is evidence of a metabolic role for IGF-I in type 1 diabetes, but it is unclear whether IGF-I acts indirectly by reducing GH secretion or has direct effects. Using stable isotopes we have investigated, on three separate occasions, the effect of a pulse of recombinant human GH, a sc injection of recombinant human IGF-I, and a placebo on glucose, lipid, and protein metabolism in subjects with type 1 diabetes during a basal insulin infusion and a hyperinsulinemic euglycemic clamp. Endogenous GH secretion was suppressed with octreotide. IGF-I reduced the hepatic glucose production rate (Ra), increased peripheral glucose uptake, and reduced protein breakdown during the basal insulin infusion (P < 0.05, P < 0.005, and P < 0.05, respectively, vs. placebo) and the hyperinsulinemic euglycemic clamp (P < 0.05, P < 0.005, and P < 0.05, respectively, vs. placebo). IGF-I had no effect on glycerol Ra, an index of lipolysis. GH increased glucose and glycerol Ra during the basal insulin infusion (P < 0.005 vs. placebo study), but the effects were no different from placebo during the clamp. In conclusion, IGF-I had a direct effect on glucose and protein metabolism, which was maintained during the hyperinsulinemic euglycemic clamp. This suggests that IGF-I acts in concert with insulin and may have an important role in maintaining glucose homeostasis and protein metabolism in type 1 diabetes.

The effect of a six-month exercise program on very low-density lipoprotein apolipoprotein B secretion in type 2 diabetes.

The dyslipidemia and insulin resistance of type 2 diabetes can be improved by aerobic exercise. The effect of 6 months supervised exercise on very low-density lipoprotein (VLDL) apolipoprotein B metabolism was investigated in patients with type 2 diabetes. Moderately obese patients (n = 18) were randomized into supervised (n = 9) and unsupervised (n = 9) exercise groups. All patients were given a training session and a personal exercise program and asked to exercise four times per week at 70% maximal oxygen uptake for 6 months. Patients in the supervised group had a weekly session with an exercise trainer. VLDL apolipoprotein (apo)B metabolism was measured with an infusion of 1-(13)C leucine before and after 6 months of the exercise program. Supervised exercise for 6 months resulted in a significant within-group decrease in percent hemoglobin A1c (P < 0.001), body fat (P < 0.004), nonesterified fatty acid (P < 0.04), and triglycerides (P < 0.05) and an increase in insulin sensitivity (P < 0.01). There was a decrease in VLDL apoB pool size (160.8 +/- 42.6 to 84.9 +/- 23.2 mg, P < 0.01) and VLDL apoB secretion rate (11.3 +/- 2.6 to 5.5 +/- 2.0 mg/kg.d, P < 0.05) with no change in fractional catabolic rate. In a between-group comparison, the decrease in VLDL apoB secretion rate in the supervised group did not achieve significance. This study demonstrates that in type 2 diabetes, a supervised exercise program reduces VLDL apoB pool size, which may be due to a decrease in VLDL apoB secretion rate.

Urinary F2-isoprostanes in young healthy children at risk for type 1 diabetes mellitus.

Oxidative stress has been linked to many diseases, but little information exists on biomarkers of oxidative stress in healthy children. The purpose of this study was to describe factors that correlate with urinary F2-isoprostanes, an indicator of oxidative stress, and to establish normal concentrations of F2-isoprostanes in children at risk to develop type 1 diabetes mellitus. Creatinine-adjusted urinary F2-isoprostanes were assessed in 342 Denver children under the age of 7 years, from whom we had collected data during 769 clinic visits from August 1997 through January 2001 (mean 2.3 visits per child). Children were identified by newborn screening for HLA-markers, of varying degrees of prediction, for the development of type 1 diabetes. Plasma antioxidants and carotenoids, age at clinic visit, vitamin supplement use, exposure to environmental tobacco smoke, gender, and race were evaluated as correlates to the degree of oxidative stress, using mixed models for longitudinal data. F2-isoprostane levels were highest in infancy and decreased nonlinearly until 7 years. Female gender, HLA-DR3/4 genotype, higher plasma gamma-tocopherol:total lipids ratio, and lower alpha-carotene:total lipids ratio correlated with higher F2-isoprostane levels. Normal values in this healthy population can be used as the basis for future studies of disease mechanisms involving oxidative stress.

Analysis of repeated measures data with clumping at zero.

Longitudinal or repeated measures data with clumping at zero occur in many applications in biometrics, including health policy research, epidemiology, nutrition, and meteorology. These data exhibit correlation because they are measured on the same subject over time or because subjects may be considered repeated measures within a larger unit such as a family. They present special challenges because of the extreme non-normality of the distributions involved. A model for repeated measures data with clumping at zero, using a mixed-effects mixed-distribution model with correlated random effects, is presented. The model contains components to model the probability of a nonzero value and the mean of nonzero values, allowing for repeated measurements using random effects and allowing for correlation between the two components. Methods for describing the effect of predictor variables on the probability of nonzero values, on the mean of nonzero values, and on the overall mean amount are given. This interpretation also applies to the mixed-distribution model for cross-sectional data. The proposed methods are illustrated with analyses of effects of several covariates on medical expenditures in 1996 for subjects clustered within households using data from the Medical Expenditure Panel Survey.

Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes.

OBJECTIVE: Insulin detemir lacks the usual propensity for insulin to cause weight gain. We investigated whether this effect was a result of reduced energy intake and/or increased energy expenditure. RESEARCH DESIGN AND METHODS: A 32-week, randomized crossover design trial was undertaken in 23 patients with type 1 diabetes. Patients on a basal-bolus regimen (with insulin aspart as the bolus insulin) were randomly assigned to insulin detemir or NPH insulin as a basal insulin for 16 weeks, followed by the other basal insulin for 16 weeks. At the end of each 16-week period, total energy expenditure, resting energy expenditure, diet-induced thermogenesis, activity energy expenditure, energy intake, weight change, glycemic control, hypoglycemic episodes, and hormones that affect satiety and fuel partitioning were measured. RESULTS: After 16 weeks, weight change was -0.69±1.85 kg with insulin detemir and +1.7±2.46 kg with NPH insulin (P<0.001). Total energy intake was significantly less with insulin detemir (2,016±501 kcal/day) than with NPH insulin (2,181±559 kcal/day) (P=0.026). There was no significant difference in any measure of energy expenditure, HbA1c percentage, or number of hypoglycemic episodes. Leptin was lower and resistin was higher with insulin detemir compared with NPH insulin (P=0.039, P=0.047). After the meal, ghrelin and pancreatic polypeptide levels (P=0.002, P=0.001) were higher with insulin detemir. CONCLUSIONS: The reduced weight gain with insulin detemir compared with NPH insulin is attributed to reduced energy intake rather than increased energy expenditure. This may be mediated by a direct or indirect effect of insulin detemir on the hormones that control satiety.

Management of varicose veins.

Varicose veins are twisted, dilated veins most commonly located on the lower extremities. Risk factors include chronic cough, constipation, family history of venous disease, female sex, obesity, older age, pregnancy, and prolonged standing. The exact pathophysiology is debated, but it involves a genetic predisposition, incompetent valves, weakened vascular walls, and increased intravenous pressure. A heavy, achy feeling; itching or burning; and worsening with prolonged standing are all symptoms of varicose veins. Potential complications include infection, leg ulcers, stasis changes, and thrombosis. Some conservative treatment options are avoidance of prolonged standing and straining, elevation of the affected leg, exercise, external compression, loosening of restrictive clothing, medical therapy, modification of cardiovascular risk factors, reduction of peripheral edema, and weight loss. More aggressive treatments include external laser treatment, injection sclerotherapy, endovenous interventions, and surgery. Comparative treatment outcome data are limited. There is little evidence to preferentially support any single treatment modality. Choice of therapy is affected by symptoms, patient preference, cost, potential for iatrogenic complications, available medical resources, insurance reimbursement, and physician training.

Effect of 6-month supervised exercise on low-density lipoprotein apolipoprotein B kinetics in patients with type 2 diabetes mellitus.

Although low-density lipoprotein (LDL) cholesterol is often normal in patients with type 2 diabetes mellitus, there is evidence for a reduced fractional catabolic rate and consequently an increased mean residence time (MRT), which can increase atherogenic risk. The dyslipidemia and insulin resistance of type 2 diabetes mellitus can be improved by aerobic exercise, but effects on LDL kinetics are unknown. The effect of 6-month supervised exercise on LDL apolipoprotein B kinetics was studied in a group of 17 patients with type 2 diabetes mellitus (mean age, 56.8 years; range, 38-68 years). Patients were randomized into a supervised group, who had a weekly training session, and an unsupervised group. LDL kinetics were measured with an infusion of 1-(13)C leucine at baseline in all groups and after 6 months of exercise in the patients. Eight body mass index-matched nondiabetic controls (mean age, 50.3 years; range, 40-67 years) were also studied at baseline only. At baseline, LDL MRT was significantly longer in the diabetic patients, whereas LDL production rate and fractional clearance rates were significantly lower than in controls. Percentage of glycated hemoglobin A(1c), body mass index, insulin sensitivity measured by the homeostasis model assessment, and very low-density lipoprotein triglyceride decreased (P < .02) in the supervised group, with no change in the unsupervised group. After 6 months, LDL cholesterol did not change in either the supervised or unsupervised group; but there was a significant change in LDL MRT between groups (P < .05) that correlated positively with very low-density lipoprotein triglyceride (r = 0.51, P < .04) and negatively with maximal oxygen uptake, a measure of fitness (r = -0.51, P = .035), in all patients. The LDL production and clearance rates did not change in either group. This study suggests that a supervised exercise program can reduce deleterious changes in LDL MRT.

The metabolites citrate, myo-inositol, and spermine are potential age-independent markers of prostate cancer in human expressed prostatic secretions.

OBJECTIVES: Due to specific physiological functions, prostatic tissues and fluids have unique metabolic profiles. In this study, proton nuclear magnetic resonance spectroscopy ((1)H-NMRS) is used to assess potential metabolic markers of prostate cancer (PCa) in human expressed prostatic secretions (EPS). METHODS: Metabolic profiles of EPS from 52 men with PCa and from 26 healthy controls were analyzed using quantitative (1)H-NMRS. The metabolites quantified included citrate, spermine, myo-inositol, lactate, alanine, phosphocholine, glutamine, acetate, and hydroxybutyrate. Logistic regression (LR) was used to model the risk of PCa based on metabolite concentrations while adjusting for age. RESULTS: The average age of the EPS donors with PCa was 58.0+/-7.0 years and 52.2+/-12.1 for the healthy donors. The median Gleason score for the men with PCa was 7 (range 5-9). The LR models indicated that the absolute concentrations of citrate, myo-inositol, and spermine were highly predictive of PCa and inversely related to the risk of PCa. The areas under the receiver operating characteristic curves (AUROC) for citrate, myo-inositol and spermine were 0.89, 0.87, and 0.79, respectively. At 90% sensitivity, these metabolites had specificities of 74%, 51%, and 34%, respectively. The LR analysis indicated that absolute levels of these three metabolites were independent of age. CONCLUSIONS: The results indicate that citrate, myo-inositol and spermine are potentially important markers of PCa in human EPS. Further, the absolute concentrations of these metabolites in EPS appear to be independent of age, increasing the potential utility of these markers due to elimination of age as a confounding variable.