Cardiometabolic Profile, Physical Activity, and Quality of Life in Breast Cancer Survivors after Different Physical Exercise Protocols: A 34-Month Follow-Up Study.

BACKGROUND: Breast cancer (BC) and cardiovascular (CV) disease share many risk factors associated with worse outcomes, in terms of cancer relapse, CV events, and quality of life (QoL), that could be counteracted by physical exercise (PE). We aimed to assess the impact of a 12-week differential PE protocol on cardiometabolic profile, QoL, CV- and BC-related long-term outcomes, and physical activity (PA) in a cohort of BC survivors (BCS) not treated with chemotherapy. METHODS: 57 BCS participated in a 12-week PE protocol [aerobic exercise training (AET) or resistance exercise training (RET)]. Anthropometric and CV evaluation, health-related (HR)-QoL, daily PA, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels were assessed before (T0) and after (T1) PE. We assessed BC and CV outcomes, HR-QoL, CV-QoL, and PA at the follow-up. RESULTS: RET improved waist circumference, DHEA-S, cortisol/DHEA-S, systolic and mean blood pressure, and ventricular/arterial coupling; AET ameliorated sagittal abdomen diameter and pulse wave velocity. Regarding HR-QoL, physical function improved only in AET group. At a mean 34 ± 3.6-month follow-up, we documented no significant differences in CV-QoL, HR-QoL, and PA or CV and BC outcomes. CONCLUSIONS: AET and RET determine specific, positive adaptations on many parameters strongly related to CV risk, CV and BC outcomes, and QoL, and should be included in any cardio-oncology rehabilitation program.

Quasiuniversal scaling in mouse-brain neuronal activity stems from edge-of-instability critical dynamics.

The brain is in a state of perpetual reverberant neural activity, even in the absence of specific tasks or stimuli. Shedding light on the origin and functional significance of such a dynamical state is essential to understanding how the brain transmits, processes, and stores information. An inspiring, albeit controversial, conjecture proposes that some statistical characteristics of empirically observed neuronal activity can be understood by assuming that brain networks operate in a dynamical regime with features, including the emergence of scale invariance, resembling those seen typically near phase transitions. Here, we present a data-driven analysis based on simultaneous high-throughput recordings of the activity of thousands of individual neurons in various regions of the mouse brain. To analyze these data, we construct a unified theoretical framework that synergistically combines a phenomenological renormalization group approach and techniques that infer the general dynamical state of a neural population, while designing complementary tools. This strategy allows us to uncover strong signatures of scale invariance that are "quasiuniversal" across brain regions and experiments, revealing that all the analyzed areas operate, to a greater or lesser extent, near the edge of instability.

Working Memory Training: Assessing the Efficiency of Mnemonic Strategies.

Recently, there has been increasing interest in techniques for enhancing working memory (WM), casting a new light on the classical picture of a rigid system. One reason is that WM performance has been associated with intelligence and reasoning, while its impairment showed correlations with cognitive deficits, hence the possibility of training it is highly appealing. However, results on WM changes following training are controversial, leaving it unclear whether it can really be potentiated. This study aims at assessing changes in WM performance by comparing it with and without training by a professional mnemonist. Two groups, experimental and control, participated in the study, organized in two phases. In the morning, both groups were familiarized with stimuli through an N-back task, and then attended a 2-hour lecture. For the experimental group, the lecture, given by the mnemonist, introduced memory encoding techniques; for the control group, it was a standard academic lecture about memory systems. In the afternoon, both groups were administered five tests, in which they had to remember the position of 16 items, when asked in random order. The results show much better performance in trained subjects, indicating the need to consider such possibility of enhancement, alongside general information-theoretic constraints, when theorizing about WM span.

Jensen's force and the statistical mechanics of cortical asynchronous states.

Cortical networks are shaped by the combined action of excitatory and inhibitory interactions. Among other important functions, inhibition solves the problem of the all-or-none type of response that comes about in purely excitatory networks, allowing the network to operate in regimes of moderate or low activity, between quiescent and saturated regimes. Here, we elucidate a noise-induced effect that we call "Jensen's force" -stemming from the combined effect of excitation/inhibition balance and network sparsity- which is responsible for generating a phase of self-sustained low activity in excitation-inhibition networks. The uncovered phase reproduces the main empirically-observed features of cortical networks in the so-called asynchronous state, characterized by low, un-correlated and highly-irregular activity. The parsimonious model analyzed here allows us to resolve a number of long-standing issues, such as proving that activity can be self-sustained even in the complete absence of external stimuli or driving. The simplicity of our approach allows for a deep understanding of asynchronous states and of the phase transitions to other standard phases it exhibits, opening the door to reconcile, asynchronous-state and critical-state hypotheses, putting them within a unified framework. We argue that Jensen's forces are measurable experimentally and might be relevant in contexts beyond neuroscience.

Time-series thresholding and the definition of avalanche size.

Avalanches whose sizes and durations are distributed as power laws appear in many contexts, from physics to geophysics and biology. Here we show that there is a hidden peril in thresholding continuous times series-from either empirical or synthetic data-for the identification of avalanches. In particular, we consider two possible alternative definitions of avalanche size used, e.g., in the empirical determination of avalanche exponents in the analysis of neural-activity data. By performing analytical and computational studies of an Ornstein-Uhlenbeck process (taken as a guiding example) we show that (1) if relatively large threshold values are employed to determine the beginning and ending of avalanches and (2) if-as sometimes done in the literature-avalanche sizes are defined as the total area (above zero) of the avalanche, then true asymptotic scaling behavior is not seen, instead the observations are dominated by transient effects. This problem-that we have detected in some recent works-leads to misinterpretations of the resulting scaling regimes.

Landau-Ginzburg theory of cortex dynamics: Scale-free avalanches emerge at the edge of synchronization.

Understanding the origin, nature, and functional significance of complex patterns of neural activity, as recorded by diverse electrophysiological and neuroimaging techniques, is a central challenge in neuroscience. Such patterns include collective oscillations emerging out of neural synchronization as well as highly heterogeneous outbursts of activity interspersed by periods of quiescence, called "neuronal avalanches." Much debate has been generated about the possible scale invariance or criticality of such avalanches and its relevance for brain function. Aimed at shedding light onto this, here we analyze the large-scale collective properties of the cortex by using a mesoscopic approach following the principle of parsimony of Landau-Ginzburg. Our model is similar to that of Wilson-Cowan for neural dynamics but crucially, includes stochasticity and space; synaptic plasticity and inhibition are considered as possible regulatory mechanisms. Detailed analyses uncover a phase diagram including down-state, synchronous, asynchronous, and up-state phases and reveal that empirical findings for neuronal avalanches are consistently reproduced by tuning our model to the edge of synchronization. This reveals that the putative criticality of cortical dynamics does not correspond to a quiescent-to-active phase transition as usually assumed in theoretical approaches but to a synchronization phase transition, at which incipient oscillations and scale-free avalanches coexist. Furthermore, our model also accounts for up and down states as they occur (e.g., during deep sleep). This approach constitutes a framework to rationalize the possible collective phases and phase transitions of cortical networks in simple terms, thus helping to shed light on basic aspects of brain functioning from a very broad perspective.

Walking training and cortisol to DHEA-S ratio in postmenopause: An intervention study.

The literature indicates that the plasma cortisol-to-dehydroepiandrosterone-sulfate (DHEA-S) ratio is a marker of health status after menopause, when a decline in both estrogen and DHEA-S and an increase in cortisol occur. An increase in the cortisol-to-DHEA-S ratio has been positively correlated with metabolic syndrome, all-cause mortality, cancer, and other diseases. The aim of this study was to investigate the effects of a walking program on the plasma cortisol-to-DHEA-S ratio in postmenopausal women. Fifty-one postmenopausal women participated in a 13-week supervised walking program, in the metropolitan area of Pescara (Italy), from June to September 2013. Participants were evaluated in April-May and September-October of the same year. The linear mixed model showed that the variation of the log10Cortisol-to-log10DHEA-S ratio was associated with the volume of exercise (p = .03). Participants having lower adherence to the walking program did not have a significantly modified log10Cortisol or log10DHEA-S, while those having the highest adherence had a significant reduction in log10Cortisol (p = .016) and a nearly significant increase in log10DHEA-S (p = .084). Walking training appeared to reduce the plasma log10Cortisol-to-log10DHEA-S ratio, although a minimum level of training was necessary to achieve this significant reduction.

Aerobic physical exercise and negative compensation of non-exercise physical activity in post-menopause: a pilot study.

BACKGROUND: Sedentarism is a risk factor for mortality that is independent of physical exercise. As indicated in the literature, there is negative compensation of non-exercise physical activity due to exercise training. The aim was to investigate potential predictor variables of physical activity compensation in post-menopausal women beginning aerobic physical exercise training. METHODS: One hundred and three post-menopausal women (mean age, 58.31±5.33 years) were eligible for the study. Metabolic markers were measured (plasma leptin, insulin, glucose), together with cardiovascular parameters and body composition. Daily physical activity was recorded objectively. Following baseline measurements, participants walked at moderate intensity on 4 days/week, for 13 weeks. RESULTS: Baseline mean intensity of daily physical activity and leptin-to-fat mass ratio (L/FMkg) were independently and negatively correlated with variations in non-exercise physical activity. High L/FMkg was associated with negative compensation of non-exercise physical activity due to aerobic physical exercise. The same was shown for participants starting their exercise training who showed high daily physical activity. CONCLUSIONS: Knowledge of both L/FMkg and baseline spontaneous physical activity of participants in exercise training are important to programme physical exercise interventions and to prevent negative non-exercise physical activity compensation due to exercise training.

Resveratrol has anti-thyroid effects both in vitro and in vivo.

Resveratrol is a natural polyphenol with antioxidant, anti-inflammatory, and antiproliferative properties. We have shown previously that resveratrol decreases sodium/iodide symporter expression and iodide uptake in thyrocytes, both in vitro and in vivo. In the present study, we further investigated the effects of resveratrol, with evaluation of the expression of additional thyroid-specific genes in the FRTL-5 rat thyroid cell line: thyroglobulin, thyroid peroxidase, TSH receptor, Nkx2-1, Foxe1 and Pax8. We observed decreased expression of these genes in FRTL-5 cells treated with 10 µM resveratrol. The effects of resveratrol was further evaluated in vivo using Sprague-Dawley rats treated with resveratrol 25 mg/kg body weight intraperitoneally, for 60 days. No clinical signs of hypothyroidism were seen, although the treated rats showed significant increase in thyroid size. Serum TSH and thyroid hormone levels were in the normal range, with significantly higher TSH seen in resveratrol-treated rats, compared with control rats. Histological and immunohistochemical analyses confirmed increased proliferative activity in the thyroid from resveratrol-treated rats. These data suggest that resveratrol acts as a thyroid disruptor and a goitrogen, which indicates the need for caution as a supplement and for therapeutic uses.

Psychophysical health status of breast cancer survivors and effects of 12 weeks of aerobic training.

The aim of this study was to analyse the health status of breast cancer survivors and the effects of 12 weeks of aerobic training. Twenty-three breast cancer survivors (51.71 ± 3.17 years) and 23 healthy women (50.73 ± 2.97 years) were investigated for body composition, daily physical activity, quality of life, salivary cortisol, and DHEA-S. Breast cancer survivors were then aerobically trained for 12 weeks. Breast cancer survivors have a worse psychophysical health than healthy women. Aerobic training increased salivary DHEA-S, aerobic fitness, self-reported health, and nocturnal sleeping time and reduced salivary cortisol in breast cancer survivors. Salivary cortisol variation correlated with change of sleeping time and self-reported health. Salivary DHEA-S correlated with change of self-reported physical pain and general health as well. Breast cancer survivors can live in a situation of continuous distress, requiring a multidisciplinary approach. Twelve weeks of aerobic training improve the psychophysical health of breast cancer survivors.

Simple unified view of branching process statistics: Random walks in balanced logarithmic potentials.

We revisit the problem of deriving the mean-field values of avalanche exponents in systems with absorbing states. These are well known to coincide with those of unbiased branching processes. Here we show that for at least four different universality classes (directed percolation, dynamical percolation, the voter model or compact directed percolation class, and the Manna class of stochastic sandpiles) this common result can be obtained by mapping the corresponding Langevin equations describing each of them into a random walker confined to the origin by a logarithmic potential. We report on the emergence of nonuniversal continuously varying exponent values stemming from the presence of small external driving - that might induce avalanche merging - that, to the best of our knowledge, has not been noticed in the past. Many of the other results derived here appear in the literature as independently derived for individual universality classes or for the branching process itself. Still, we believe that a simple and unified perspective as the one presented here can help (1) clarify the overall picture, (2) underline the superuniversality of the behavior as well as the dependence on external driving, and (3) avoid the common existing confusion between unbiased branching processes (equivalent to a random walker in a balanced logarithmic potential) and standard (unconfined) random walkers.

Physical exercises for breast cancer survivors: effects of 10 weeks of training on upper limb circumferences.

[Purpose] The aims of this study were to verify the effects on upper limb circumferences and total body extracellular water of 10 weeks of Nordic Walking (NW) and Walking (W), both alone and combined with a series of exercises created for breast cancer survivors, the ISA method. [Subjects and Methods] Twenty breast cancer survivors were randomly assigned to 4 different training groups and evaluated for upper limb circumferences, total body and extracellular water. [Results] The breast cancer survivors who performed NW, alone and combined with the ISA method, and Walking combined with the ISA method (but not alone) showed significantly reduced arm and forearm circumferences homolateral to the surgical intervention. [Conclusion] For breast cancer survivors, NW, alone and combined with the ISA method, and Walking combined with the ISA method should be prescribed to prevent the onset and to treat light forms of upper limb lymphedema because Walking training practiced alone had no significant effect on upper limb circumference reduction.

Self-Organized Bistability Associated with First-Order Phase Transitions.

Self-organized criticality elucidates the conditions under which physical and biological systems tune themselves to the edge of a second-order phase transition, with scale invariance. Motivated by the empirical observation of bimodal distributions of activity in neuroscience and other fields, we propose and analyze a theory for the self-organization to the point of phase coexistence in systems exhibiting a first-order phase transition. It explains the emergence of regular avalanches with attributes of scale invariance that coexist with huge anomalous ones, with realizations in many fields.

Acute and delayed effects of high intensity interval resistance training organization on cortisol and testosterone production.

BACKGROUND: The use of high-intensity interval training (HIIT) is widely diffused as strategy to enhance aerobic fitness and body composition. In order to offer a more complete training, resistance exercises have been added to HIIT (HIIRT). Aims of our study were to characterize both heart rate and hormonal responses elicited by three different protocols of HIIRT having the same exercises, the same load and number of repetitions for each exercise. METHODS: Eight healthy trained men (28.61±3.51 years) performed three different workouts: exercise order, recovery and speed of execution were differently organized according to workout. Salivary samples were collected before and after each workout, at 11:00 p.m. and at 7:00 a.m. of the following day. Salive was also collected during a non-training day. Before and after the workout, plasma lactate was measured while a beat-to-beat heart rate recording was executed during each workout. Cortisol (C) and testosterone (T) were measured in salivary samples. RESULTS: Workouts elicited the same heart rate response while random organization seems to elicit the highest lactate, C and T increases. Also when we studied the effects of workouts on prolonged hormones production we observed that workout organization influenced post-exercise hormonal production until the following morning modifying their physiological trend. CONCLUSIONS: Even if exercises, load and number of repetitions were maintained fixed, exercise order, structured recovery and speed of execution determined different acute and prolonged effects. The knowledge of these responses is very important because may positively or negatively influence performance and health.

Nordic Walking and the Isa Method for Breast Cancer Survivors: Effects on Upper Limb Circumferences and Total Body Extracellular Water - a Pilot Study.

BACKGROUND: The negative side effects of breast cancer treatments can include upper limb lymphoedema. The growing literature indicates that Nordic walking is an effective discipline against several disease symptoms. The aim of this study was to determine whether introduction to Nordic walking alone is effective against total body extracellular water and upper limb circumferences in breast cancer survivors compared to its combination with a series of specifically created exercises (i.e. the Isa method). METHODS: 16 breast cancer survivors (49.09 ± 2.24 years) were recruited and randomly assigned to 1 of 2 different training groups. RESULTS: 10 lessons on Nordic walking technique plus the Isa method significantly reduced both extracellular body water and the extracellular-to-total body water ratio (p = 0.01 for both), and also the circumference of the upper limb, (both relaxed arm and forearm circumferences) (p = 0.01 for all), whereas Nordic walking alone did not. CONCLUSIONS: Introduction to Nordic walking does not seem to affect lymphoedema in breast cancer survivors. This might be because novice Nordic Walkers do not adequately generate an effective muscular pump through coordination of the alternated bimanual open-close cycle. The Isa method appears to close this gap.

Reduced Lysosomal Acid Lipase Activity in Adult Patients With Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation and mechanisms involved in its pathogenesis are not fully explained. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with fatty liver. LAL activity (nmol/spot/h) was measured in 100 adult healthy subjects (HS) and in 240 NAFLD patients. A sub-analysis on 35 patients with biopsy-proven non-alcoholic steatohepatitis (NASH) was performed. Median LAL activity was 1.15 (0.95-1.72) in HS. It was significantly reduced in NAFLD [0.78 (0.61-1.01), p < 0.001 vs. HS]. A further reduction was observed in the subgroup of NASH [0.67 (0.51-0.77), p < 0.001 vs. HS]. Patients with LAL activity below median had higher values of serum total cholesterol (p < 0.05) and LDL-c (p < 0.05), and increased serum liver enzymes (ALT, p < 0.001; AST, p < 0.01; GGT, p < 0.01). At multivariable logistic regression analysis, factors associated with LAL activity below median were ALT (OR: 1.018, 95% CI 1.004-1.032, p = 0.011) and metabolic syndrome (OR: 2.551, 95% CI 1.241-5.245, p = 0.011), whilst statin use predicted a better LAL function (OR: 0.464, 95% CI 0.248-0.866, p = 0.016). Our findings suggest a strong association between impaired LAL activity and NAFLD. A better knowledge of the role of LAL may provide new insights in NAFLD pathogenesis.

Microscopic mechanism for self-organized quasiperiodicity in random networks of nonlinear oscillators.

Self-organized quasiperiodicity is one of the most puzzling dynamical phases observed in systems of nonlinear coupled oscillators. The single dynamical units are not locked to the periodic mean field they produce, but they still feature a coherent behavior, through an unexplained complex form of correlation. We consider a class of leaky integrate-and-fire oscillators on random sparse and massive networks with dynamical synapses, featuring self-organized quasiperiodicity, and we show how complex collective oscillations arise from constructive interference of microscopic dynamics. In particular, we find a simple quantitative relationship between two relevant microscopic dynamical time scales and the macroscopic time scale of the global signal. We show that the proposed relation is a general property of collective oscillations, common to all the partially synchronous dynamical phases analyzed. We argue that an analogous mechanism could be at the origin of similar network dynamics.

LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism.

OBJECTIVES: Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. METHODS: Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. RESULTS: Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 µmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. CONCLUSION: Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation.

Resveratrol inhibits sodium/iodide symporter gene expression and function in rat thyroid cells.

Resveratrol is a polyphenol found in grapes and berries that has antioxidant, antiproliferative and anti-inflammatory properties. For these reasons, it is available as a dietary supplement, and it is under investigation in several clinical trials. Few data are available regarding the effects of resveratrol on thyroid function. A previous study showed that resveratrol transiently increases iodide influx in FRTL-5 rat thyroid cells. Indeed, this increase arises after short treatment times (6-12 h), and no further effects are seen after 24 h. The aim of the present study was to investigate the effects of resveratrol on iodide uptake and sodium/iodide symporter expression in thyroid cells after longer times of treatment. For this purpose, the effects of resveratrol were evaluated both in vitro and in vivo using the rat thyroid FRTL-5 cell line and Sprague-Dawley rats, respectively. In FRTL-5 cells, resveratrol decreased the sodium/iodide symporter RNA and protein expression as a function of time. Furthermore, resveratrol decreased cellular iodide uptake after 48 h of treatment. The inhibitory effect of resveratrol on iodide uptake was confirmed in vivo in Sprague-Dawley rats. This study demonstrates that with longer-term treatment, resveratrol is an inhibitor of sodium/iodide symporter gene expression and function in the thyroid. These data suggest that resveratrol can act as a thyroid disruptor, which indicates the need for caution as a supplement and in therapeutic use.

The flavonoid quercetin inhibits thyroid-restricted genes expression and thyroid function.

Quercetin is the most abundant flavonoid present in a broad range of fruit and vegetables. Furthermore, quercetin is available as dietary supplements that are based on its antioxidant, antiproliferative and anti-inflammatory properties. However, concerns have been raised about the potential toxic effects of excessive intake of quercetin, and several studies have demonstrated that flavonoids, included quercetin, can interfere with thyroid function. In a previous report, we showed that quercetin inhibits thyroid-cell growth and iodide uptake. The latter effect was associated with down-regulation of sodium/iodide symporter gene expression. In the present study, we have evaluated the effects of quercetin on the expression of other thyroid-restricted genes, and we show that quercetin decreases the expression of the thyrotropin receptor, thyroid peroxidase and thyroglobulin genes. We further investigated the inhibitory effects of quercetin on thyroid function in vivo through evaluation of radioiodine uptake in the Sprague-Dawley rat, which was significantly decreased after 14 days of quercetin treatment. These data confirm that quercetin can act as a thyroid disruptor, and they suggest that caution is needed in its supplemental and therapeutic use.