To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for ...predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean); -0.522, 0.821 (median); -0.569, 0.854 (10th percentile); -0.556, 0.854 (25th percentile); -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.
Computer-aided diagnosis (CAD) systems are increasingly being used in clinical settings to report multi-parametric magnetic resonance imaging (mp-MRI) of the prostate. Usually, CAD systems ...automatically highlight cancer-suspicious regions to the radiologist, reducing reader variability and interpretation errors. Nevertheless, implementing this software requires the selection of which mp-MRI parameters can best discriminate between malignant and non-malignant regions. To exploit functional information, some parameters are derived from dynamic contrast-enhanced (DCE) acquisitions. In particular, much CAD software employs pharmacokinetic features, such as K
and k
, derived from the Tofts model, to estimate a likelihood map of malignancy. However, non-pharmacokinetic models can be also used to describe DCE-MRI curves, without any requirement for prior knowledge or measurement of the arterial input function, which could potentially lead to large errors in parameter estimation. In this work, we implemented an empirical function derived from the phenomenological universalities (PUN) class to fit DCE-MRI. The parameters of the PUN model are used in combination with T2-weighted and diffusion-weighted acquisitions to feed a support vector machine classifier to produce a voxel-wise malignancy likelihood map of the prostate. The results were all compared to those for a CAD system based on Tofts pharmacokinetic features to describe DCE-MRI curves, using different quality aspects of image segmentation, while also evaluating the number and size of false positive (FP) candidate regions. This study included 61 patients with 70 biopsy-proven prostate cancers (PCa). The metrics used to evaluate segmentation quality between the two CAD systems were not statistically different, although the PUN-based CAD reported a lower number of FP, with reduced size compared to the Tofts-based CAD. In conclusion, the CAD software based on PUN parameters is a feasible means with which to detect PCa, without affecting segmentation quality, and hence it could be successfully applied in clinical settings, improving the automated diagnosis process and reducing computational complexity.
Aim
Striatin (Strn) is a scaffold protein expressed in cardiomyocytes (CMs) and alteration of its expression are described in various cardiac diseases. However, the alteration underlying its ...pathogenicity have been poorly investigated.
Methods
We studied the role(s) of cardiac Strn gene (STRN) by comparing the functional properties of CMs, generated from Strn‐KO and isogenic WT mouse embryonic stem cell lines.
Results
The spontaneous beating rate of Strn‐KO CMs was faster than WT cells, and this correlated with a larger fast INa conductance and no changes in If. Paced (2–8 Hz) Strn‐KO CMs showed prolonged action potential (AP) duration in comparison with WT CMs and this was not associated with changes in ICaL and IKr. Motion video tracking analysis highlighted an altered contraction in Strn‐KO CMs; this was associated with a global increase in intracellular Ca2+, caused by an enhanced late Na+ current density (INaL) and a reduced Na+/Ca2+ exchanger (NCX) activity and expression. Immunofluorescence analysis confirmed the higher Na+ channel expression and a more dynamic microtubule network in Strn‐KO CMs than in WT. Indeed, incubation of Strn‐KO CMs with the microtubule stabilizer taxol, induced a rescue (downregulation) of INa conductance toward WT levels.
Conclusion
Loss of STRN alters CMs electrical and contractile profiles and affects cell functionality by a disarrangement of Strn‐related multi‐protein complexes. This leads to impaired microtubules dynamics and Na+ channels trafficking to the plasma membrane, causing a global Na+ and Ca2+ enhancement.
Purpose
Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15–30% of cases, therefore it ...would be useful to assess if pretreatment of
18
F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC.
Methods
Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models.
Results
In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index).
Conclusions
If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.
The effects of resistance training programs on strength, power, and military occupational task performances in women were examined.
Untrained women aged (mean +/- SD) 23 +/- 4 yr were matched and ...randomly placed in total- (TP, N = 17 and TH, N = 18) or upper-body resistance training (UP, N = 18 and UH, N = 15), field (FLD, N = 14), or aerobic training groups (AER, N = 11). Two periodized resistance training programs (with supplemental aerobic training) emphasized explosive exercise movements using 3- to 8-RM training loads (TP, UP), whereas the other two emphasized slower exercise movements using 8- to 12-RM loads (TH, UH). The FLD group performed plyometric and partner exercises. Subjects were tested for body composition, strength, power, endurance, maximal and repetitive box lift, 2-mile loaded run, and U.S. Army Physical Fitness Tests before (T0) and after 3 (T3) and 6 months of training (T6). For comparison, untrained men (N = 100) (MEN) were tested once.
Specific training programs resulted in significant increases in body mass (TP), 1-RM squat (TP, TH, FLD), bench press (all except AER), high pull (TP), squat jump (TP, TH, FLD), bench throw (all except AER), squat endurance (all except AER), 1-RM box lift (all except aerobic), repetitive box lift (all), push-ups (all except AER), sit-ups (all except AER), and 2-mile run (all).
Strength training improved physical performances of women over 6 months and adaptations in strength, power, and endurance were specific to the subtle differences (e.g., exercise choice and speeds of exercise movement) in the resistance training programs (strength/power vs strength/hypertrophy). Upper- and total-body resistance training resulted in similar improvements in occupational task performances, especially in tasks that involved upper-body musculature. Finally, gender differences in physical performance measures were reduced after resistance training in women, which underscores the importance of such training for physically demanding occupations.
Dynamic contrast-enhanced study in magnetic resonance imaging (DCE-MRI) is an important tool in oncology to visualize tissues vascularization and to define tumour aggressiveness on the basis of an ...altered perfusion and permeability. Pharmacokinetic models are generally used to extract hemodynamic parameters, providing a quantitative description of the contrast uptake and wash-out. Empirical functions can also be used to fit experimental data without the need of any assumption about tumour physiology, as in pharmacokinetic models, increasing their diagnostic utility, in particular when automatic diagnosis systems are implemented on the basis of an MRI multi-parametric approach. Phenomenological universalities (PUN) represent a novel tool for experimental research and offer a simple and systematic method to represent a set of data independent of the application field. DCE-MRI acquisitions can thus be advantageously evaluated by the extended PUN class, providing a convenient diagnostic tool to analyse functional studies, adding a new set of features for the classification of malignant and benign lesions in computer aided detection systems. In this work the Tofts pharmacokinetic model and the class EU1 generated by the PUN description were compared in the study of DCE-MRI of the prostate, evaluating complexity of model implementation, goodness of fitting results, classification performances and computational cost. The mean R² obtained with the EU1 and Tofts model were equal to 0.96 and 0.90, respectively, and the classification performances achieved by the EU1 model and the Tofts implementation discriminated malignant from benign tissues with an area under the receiver operating characteristic curve equal to 0.92 and 0.91, respectively. Furthermore, the EU1 model has a simpler functional form which reduces implementation complexity and computational time, requiring 6 min to complete a patient elaboration process, instead of 8 min needed for the Tofts model analysis.
The purpose of this investigation was to determine the long-term training adaptations associated with low-volume circuit-type versus periodized high-volume resistance training programs in women.
34 ...healthy, untrained women were randomly placed into one of the following groups: low-volume, single-set circuit (SSC; N = 12); periodized high-volume multiple-set (MS; N = 12); or nonexercising control (CON) group (N = 10). The SSC group performed one set of 8-12 repetitions to muscular failure 3 d x wk(-1). The MS group performed two to four sets of 3-15 repetitions with periodized volume and intensity 4 d x wk(-1). Muscular strength, power, speed, endurance, anthropometry, and resting hormonal concentrations were determined pretraining (T1), after 12 wk (T2), and after 24 wk of training (T3).
1-RM bench press and leg press, and upper and lower body local muscular endurance increased significantly (P < or = 0.05) at T2 for both groups, but only MS showed a significant increase at T3. Muscular power and speed increased significantly at T2 and T3 only for MS. Increases in testosterone were observed for both groups at T2 but only MS showed a significant increase at T3. Cortisol decreased from T1 to T2 and from T2 to T3 in MS. Insulin-like growth factor-1 increased significantly at T3 for SSC and at T2 and T3 for MS. No changes were observed for growth hormone in any of the training groups.
Significant improvements in muscular performance may be attained with either a low-volume single-set program or a high-volume, periodized multiple-set program during the first 12 wk of training in untrained women. However, dramatically different training adaptations are associated with specific domains of training program design which contrast in speed of movement, exercise choices and use of variation (periodization) in the intensity and volume of exercise.
Abstract We investigated the effect of a single administration of recombinant human erythropoietin (rhEPO) on the preservation of the ventral white matter of rats at 4 weeks after contusive spinal ...cord injury (SCI), a time at which functional recovery is significantly improved in comparison to the controls Gorio A, Necati Gokmen N, Erbayraktar S, Yilmaz O, Madaschi L, Cichetti C, Di Giulio AM, Enver Vardar E, Cerami A, Brines M (2002) Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci U S A 99:9450–9455; Gorio A, Madaschi L, Di Stefano B, Carelli S, Di Giulio AM, De Biasi S, Coleman T, Cerami A, Brines M (2005) Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury. Proc Natl Acad Sci U S A 102:16379–16384. Specifically, we examined, by morphological and cytochemical methods combined with light, confocal and electron microscopy, i) myelin preservation, ii) activation of adult oligodendrocyte progenitors (OPCs) identified for the expression of NG2 transmembrane proteoglycan, iii) changes in the amount of the chondroitin sulfate proteoglycans neurocan, versican and phosphacan and of their glycosaminoglycan component labeled with Wisteria floribunda lectin, and iv) ventral horn density of the serotonergic plexus as a marker of descending motor control axons. Injured rats received either saline or a single dose of rhEPO within 30 min after SCI. The results showed that the significant improvement of functional outcome observed in rhEPO-treated rats was associated with a better preservation of myelin in the ventral white matter. Moreover, the significant increase of both the number of NG2-positive OPCs and the labeling for Nogo-A, a marker of differentiated oligodendrocytes, suggested that rhEPO treatment could result in the generation of new myelinating oligodendrocytes. Sparing of fiber tracts in the ventral white matter was confirmed by the increased density of the serotonergic plexus around motor neurons. As for chondroitin sulfate proteoglycans, only phosphacan, increased in saline-treated rats, returned to normal levels in rhEPO group, probably reflecting a better maintenance of glial-axolemmal relationships along nerve fibers. In conclusion, this investigation expands previous studies supporting the pleiotropic neuroprotective effect of rhEPO on secondary degenerative response and its therapeutic potential for the treatment of SCI and confirms that the preservation of the ventral white matter, which contains descending motor pathways, may be critical for limiting functional deficit.
The purpose of this study was to examine the effect of creatine supplementation in conjunction with resistance training on physiological adaptations including muscle fiber hypertrophy and muscle ...creatine accumulation.
Nineteen healthy resistance-trained men were matched and then randomly assigned in a double-blind fashion to either a creatine (N = 10) or placebo (N = 9) group. Periodized heavy resistance training was performed for 12 wk. Creatine or placebo capsules were consumed (25 g x d(-1)) for 1 wk followed by a maintenance dose (5 g x d(-1)) for the remainder of the training.
After 12 wk, significant (P < or = 0.05) increases in body mass and fat-free mass were greater in creatine (6.3% and 6.3%, respectively) than placebo (3.6% and 3.1%, respectively) subjects. After 12 wk, increases in bench press and squat were greater in creatine (24% and 32%, respectively) than placebo (16% and 24%, respectively) subjects. Compared with placebo subjects, creatine subjects demonstrated significantly greater increases in Type I (35% vs 11%), IIA (36% vs 15%), and IIAB (35% vs 6%) muscle fiber cross-sectional areas. Muscle total creatine concentrations were unchanged in placebo subjects. Muscle creatine was significantly elevated after 1 wk in creatine subjects (22%), and values remained significantly greater than placebo subjects after 12 wk. Average volume lifted in the bench press during training was significantly greater in creatine subjects during weeks 5-8. No negative side effects to the supplementation were reported.
Creatine supplementation enhanced fat-free mass, physical performance, and muscle morphology in response to heavy resistance training, presumably mediated via higher quality training sessions.
The purpose of this study was to compare changes in maximal strength, power, and muscular endurance after 12 wk of periodized heavy-resistance training directly supervised by a personal trainer (SUP) ...versus unsupervised training (UNSUP).
Twenty moderately trained men aged 24.6 +/- 1.0 yr (mean +/- SE) were randomly assigned to either the SUP group (N = 10) or the UNSUP group (N = 8). Both groups performed identical linear periodized resistance training programs consisting of preparatory (10-12 repetitions maximum (RM)), hypertrophy (8 to 10-RM), strength (5 to 8-RM), and peaking phases (3 to 6-RM) using free-weight and variable-resistance machine exercises. Subjects were tested for maximal squat and bench press strength (1-RM), squat jump power output, bench press muscular endurance, and body composition at week 0 and after 12 wk of training.
Mean training loads (kg per set) per week were significantly (P < 0.05) greater in the SUP group than the UNSUP group at weeks 7 through 11 for the squat, and weeks 3 and 7 through 12 for the bench press exercises. The rates of increase (slope) of squat and bench press kg per set were significantly greater in the SUP group. Maximal squat and bench press strength were significantly greater at week 12 in the SUP group. Squat and bench press 1-RM, and mean and peak power output increased significantly after training in both groups. Relative local muscular endurance (80% of 1-RM) was not compromised in either group despite significantly greater loads utilized in bench press muscular endurance testing after training. Body mass, fat mass, and fat-free mass increased significantly after training in the SUP group.
Directly supervised, heavy-resistance training in moderately trained men resulted in a greater rate of training load increase and magnitude which resulted in greater maximal strength gains compared with unsupervised training.
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