Water dynamics in human cancer and non-cancer tissues.

Normal-to-malignant transformation is a poorly understood process associated with cellular biomechanical properties. These are strongly dependent on the dynamical behaviour of water, known to play a fundamental role in normal cellular activity and in the maintenance of the three-dimensional architecture of the tissue and the functional state of biopolymers. In this study, quasi-elastic neutron scattering was used to probe the dynamical behaviour of water in human cancer specimens and their respective surrounding normal tissue from breast and tongue, as an innovative approach for identifying particular features of malignancy. This methodology has been successfully used by the authors in human cells and was the first study of human tissues by neutron scattering techniques. A larger flexibility was observed for breast versus tongue tissues. Additionally, different dynamics were found for malignant and non-malignant specimens, depending on the tissue: higher plasticity for breast invasive cancer versus the normal, and an opposite effect for tongue. The data were interpreted in the light of two different water populations within the samples: one displaying bulk-like dynamics (extracellular and intracellular/cytoplasmic) and another with constrained flexibility (extracellular/interstitial and intracellular/hydration layers).

Analyzing similarities in genome sequences.

This article investigates aspects of similarity between complete sequences of mitochondrial DNA by determining the distribution of the relative frequencies of words with different lengths and the characteristics of their relevance throughout the sequences. The degree of similarity is obtained by comparing the distances between words contained within these sequences. Our results indicate that the best groupings among different species depend on the lengths of words and their respective relative frequencies. We also observed that the longer the word the more consistent the grouping between the sequences becomes. The application of our results, together with the perspective of analyzing DNA sequences belonging to a single biological species, may be important for the construction of phylogenetic trees, which are appropriate structures for understanding the evolutionary history of the species.

Phase-amplitude coupling and the BOLD signal: A simultaneous intracranial EEG (icEEG) - fMRI study in humans performing a finger-tapping task.

Although it has been consistently found that local blood-oxygen-level-dependent (BOLD) changes are better modelled by a combination of the power of multiple EEG frequency bands rather than by the power of a unique band alone, the local electro-haemodynamic coupling function is not yet fully characterised. Electrophysiological studies have revealed that the strength of the coupling between the phase of low- and the amplitude of high- frequency EEG activities (phase-amplitude coupling - PAC) has an important role in brain function in general, and in preparation and execution of movement in particular. Using electrocorticographic (ECoG) and functional magnetic resonance imaging (fMRI) data recorded simultaneously in humans performing a finger-tapping task, we investigated the single-trial relationship between the amplitude of the BOLD signal and the strength of PAC and the power of α, ß, and γ bands, at a local level. In line with previous studies, we found a positive correlation for the γ band, and negative correlations for the PACßγ strength, and the α and ß bands. More importantly, we found that the PACßγ strength explained variance of the amplitude of the BOLD signal that was not explained by a combination of the α, ß, and γ band powers. Our main finding sheds further light on the distinct nature of PAC as a functionally relevant mechanism and suggests that the sensitivity of EEG-informed fMRI studies may increase by including the PAC strength in the BOLD signal model, in addition to the power of the low- and high- frequency EEG bands.

A study of the electro-haemodynamic coupling using simultaneously acquired intracranial EEG and fMRI data in humans.

In current fMRI studies designed to map BOLD changes related to interictal epileptiform discharges (IED), which are recorded on simultaneous EEG, the information contained in the morphology and field extent of the EEG events is exclusively used for their classification. Usually, a BOLD predictor based on IED onset times alone is constructed, effectively treating all events as identical. We used intracranial EEG (icEEG)-fMRI data simultaneously recorded in humans to investigate the effect of including any of the features: amplitude, width (duration), slope of the rising phase, energy (area under the curve), or spatial field extent (number of contacts over which the sharp wave was observed) of the fast wave of the IED (the sharp wave), into the BOLD model, to better understand the neurophysiological origin of sharp wave-related BOLD changes, in the immediate vicinity of the recording contacts. Among the features considered, the width was the only one found to explain a significant amount of additional variance, suggesting that the amplitude of the BOLD signal depends more on the duration of the underlying field potential (reflected in the sharp wave width) than on the degree of neuronal activity synchrony (reflected in the sharp wave amplitude), and, consequently, that including inter-event variations of the sharp wave width in the BOLD signal model may increase the sensitivity of forthcoming EEG-fMRI studies of epileptic activity.

AquaTrainer® Snorkel does not Increase Hydrodynamic Drag but Influences Turning Time.

Our purpose was to verify if the use of the new AquaTrainer(®) respiratory snorkel lead to an increase of front crawl hydrodynamic drag and whether the constraint of using an adapted turning technique influences its corresponding turning time. 12 swimmers performed 2 (without and with snorkel) 12×25 front crawl repetitions from low to maximal velocity on the measuring active drag system. Complementarily, 3 swimming turns were compared: open turn with snorkel, tumble turn and open turn without snorkel. Drag values were similar without vs. with snorkel at 0.9, 1.1, 1.3, 1.5 and 1.7 m.s(-1) velocities: 15.84 ±5.32 vs. 16.18±4.81, 25.60±6.69 vs. 26.03±6.17, 38.37±8.04 vs. 38.88±7.56, 54.64±10.06 vs. 55.08±9.55, 74.77±14.09 vs. 74.92±13.14 N, (respectively, p≥0.05), and high agreement between conditions was observed (p<0.01). Front crawl swimming with snorkel using the open turn implied an increase in turning time of 14.2 and 5.1% than the tumble turn and open turn without the apparatus (p<0.01). AquaTrainer(®) snorkel does not lead to an increase in active drag during front crawl performed at a large range of velocities and, consequently, the metabolic energy necessary to overcome total drag will not be affected. However, turning with it requires an additional time that should be taken into account in scientific research and training conditions.

A Correlational Analysis of Tethered Swimming, Swim Sprint Performance and Dry-land Power Assessments.

Swimmers are often tested on both dry-land and in swimming exercises. The aim of this study was to test the relationships between dry-land, tethered force-time curve parameters and swimming performances in distances up to 200 m. 10 young male high-level swimmers were assessed using the maximal isometric bench-press and quarter-squat, mean propulsive power in jump-squat, squat and countermovement jumps (dry-land assessments), peak force, average force, rate of force development (RFD) and impulse (tethered swimming) and swimming times. Pearson product-moment correlations were calculated among the variables. Peak force and average force were very largely correlated with the 50- and 100-m swimming performances (r=- 0.82 and -0.74, respectively). Average force was very-largely/largely correlated with the 50- and 100-m performances (r=- 0.85 and -0.67, respectively). RFD and impulse were very-largely correlated with the 50-m time (r=- 0.72 and -0.76, respectively). Tethered swimming parameters were largely correlated (r=0.65 to 0.72) with mean propulsive power in jump-squat, squat-jump and countermovement jumps. Finally, mean propulsive power in jump-squat was largely correlated (r=- 0.70) with 50-m performance. Due to the significant correlations between dry-land assessments and tethered/actual swimming, coaches are encouraged to implement strategies able to increase leg power in sprint swimmers.

VO2 kinetics and metabolic contributions during full and upper body extreme swimming intensity.

PURPOSE: Our purpose was to characterize the oxygen uptake ([Formula: see text]) kinetics, assess the energy systems contributions and determine the energy cost when swimming front crawl at extreme intensity. Complementarily, we compared swimming full body with upper body only. METHODS: Seventeen swimmers performed a 100 m maximal front crawl in two conditions: once swimming with full body and other using only the upper propulsive segments. The [Formula: see text] was continuously measured using a telemetric portable gas analyser (connected to a respiratory snorkel), and the capillary blood samples for lactate concentration analysis were collected. RESULTS: A sudden increase in [Formula: see text] in the beginning of exercise, which continuously rose until the end of the bout (time: 63.82 ± 3.38 s; [Formula: see text]: 56.07 ± 5.19 ml min(-1) kg(-1); [Formula: see text] amplitude: 41.88 ± 4.74 ml min(-1) kg(-1); time constant: 12.73 ± 3.09 s), was observed. Aerobic, anaerobic lactic and alactic pathways were estimated and accounted for 43.4, 33.1 and 23.5 % of energy contribution and 1.16 ± 0.10 kJ m(-1) was the energy cost. Complementarily, the absence of lower limbs lead to a longer time to cover 100 m (71.96 ± 5.13 s), slower [Formula: see text] kinetics, lower aerobic and anaerobic (lactic and alactic) energy production and lower energy cost. CONCLUSION: Despite the short duration of the event, the aerobic energy contribution covers about 50 % of total metabolic energy liberation, highlighting that both aerobic and anaerobic energy processes should be developed to improve the 100 m swimming performance. Lower limbs action provided an important contribution in the energy availability in working muscles being advised its full use in this short duration and very high-intensity event.

Reproducibility of hypocapnic cerebrovascular reactivity measurements using BOLD fMRI in combination with a paced deep breathing task.

It has recently been proposed that hypocapnic cerebrovascular reactivity (CVR) can be assessed by measuring the blood oxygenation level dependent (BOLD) response to paced deep breathing (PDB) tasks inducing mild hypocapnia and vasoconstriction. In this work, we aim to assess the test-retest reproducibility and inter-subject variability of BOLD CVR measurements obtained using a PDB task and different methods to analyse the associated BOLD signal. The respiratory protocol consisted of alternating 40s of PDB with normal free breathing; expired CO2 pressure levels (PETCO2) were continuously monitored. CVR was quantified using either a timecourse curve analysis (TCA) approach, where the magnitude of response peaks is emphasized, or general linear modelling (GLM) including optimisation of the BOLD response latencies. The GLM fit was carried out using two types of response regressors: one that was computed as the convolution of PETCO2 traces with a gamma function and another that consisted of the convolution of PDB paradigm blocks with a physiological model of the respiratory response. Haemodynamic response latencies were optimised either on a voxel basis or for the whole imaging region. We found that the GLM method based on PDB task or PETCO2 traces and voxelwise optimisation of response latencies provided the most reproducible measures of CVR. For the average grey matter CVR, the inter-subject coefficient of variation (CVinter) / intra-subject coefficient of variation (CVintra) / intra-class correlation coefficient (ICC) were 20%/8%/0.8 and 27%/8%/0.9, using the task and PETCO2 timecourses, respectively. In terms of the spatial reproducibility, the group mean (±standard deviation) of the spatial ICC (ICCspatial) was 1.04±0.23 and 1.02±0.26, for the task and PETCO2 timecourses, respectively. These results indicate generally good reproducibility of the hypocapnic CVR maps obtained using the proposed PDB task and analysis methodology. This suggests that such protocol may therefore offer a promising alternative to conventional vasoactive challenges, which avoids their discomfort and difficulty.

Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study.

To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm(2) and 18% of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2- subgroup, a mitotic count <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and <0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2- subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.

Cardiac regeneration and cellular therapy: is there a benefit of exercise?

Cardiovascular diseases (CVD) are a global epidemic in developed countries. Cumulative evidence suggests that myocyte formation is preserved during postnatal life, in adulthood or senescence, suggesting the existence of a growth reserve of the heart throughout lifespan. Several medical therapeutic approaches to CVD have considerably improved the clinical outcome for patients. Intense interest has been focused on regenerative medicine as an emerging strategy for CVD. Cellular therapeutic approaches have been proposed for enhancing survival and propagation of stem cells in myocardium, leading to cardiac cellular repair. Strong epidemiological and clinical data exists concerning the impact of regular physical exercise on cardiovascular health. Several mechanisms of acute and chronic exercise-induced cardiovascular adaptations to exercise have been presented, considering primary and secondary prevention of CVD. In this context, exercise-related improvements in the function and regeneration of the cardiovascular system may be associated with the exercise-induced activation, mobilization, differentiation, and homing of stem and progenitor cells. In this review several topics will be addressed concerning the relation between exercise, recruitment and biological activity of blood-circulating progenitor cells and resident cardiac stem cells. We hypothesize that exercise-induced stem cell activation may enhance overall heart function and improve the efficacy of cardiac cellular therapeutic protocols.

Acute hepatitis E complicated by Guillain-Barre syndrome in Portugal, December 2012--a case report.

Autochthonous hepatitis E virus (HEV) infection has been increasingly reported in Europe and the United States, mostly arising from genotype 3 and less frequently genotype 4. We report here on a patient with HEV genotype 3a infection complicated by Guillain-Barré syndrome in Portugal in December 2012. We draw attention to the diagnosis of autochthonous HEV infection and to its rare, but important, neurological complications.

Kinematic and electromyographic changes during 200 m front crawl at race pace.

The purpose of this study was to analyse eventual kinematic and electromyographic changes during a maximal 200 m front crawl at race pace. 10 male international level swimmers performed a 200 m maximal front crawl test. Images were recorded by 2 above and 4 under water cameras, and electromyographic signals (EMG) of 7 upper and lower limbs muscles were analysed for 1 stroke cycle in each 50 m lap. Capillary blood lactate concentrations were collected before and after the test. The variables of interest were: swimming speed, stroke length, stroke and kick frequency, hand angular velocity, upper limb and foot displacement, elbow angle, shoulder and roll angle, duration of stroke phases, and EMG for each muscle in each stroke phase. Generally, the kinematic parameters decreased, and a relative duration increased for the entry and pull phases and decreased for the recovery phase. Muscle activation of flexor carpi radialis, biceps brachii, triceps brachii, peitoral major and upper trapezius increased during specific stroke phases over the test. Blood lactate concentration increased significantly after the test. These findings suggest the occurrence of fatigue, characterised by changes in kinematic parameters and selective changes in upper limbs muscle activation according to muscle action.

Intracycle velocity variation of the body centre of mass in front crawl.

Our aim was to determine the 3-dimensional intracycle velocity variation (IVV) of the body centre of mass during a 200-m front crawl event, and to analyse its relation with the segmental hand kinematics and the velocity (v) changes. 10 high-level male swimmers performed a 200-m front crawl swim at maximal intensity. 2 above- and 4 underwater cameras were used to record one complete non-breathing cycle for each 50-m lap, and APASystem was used for imaging processing. The coefficient of variation was calculated to assess the IVV in the horizontal (x), vertical (y), and lateral (z) axes; hand kinematics was also computed. IVV remained stable across the 200 m, and significant correlations were found between vx and vmaxx (r=0.55), vminx (r = 0.68), IVVx (r = -0.45), and IVVz (r = -0.45) (all p≤0.01). In addition, IVVx was correlated with the backward horizontal amplitude normalized to stroke length (r = 0.54), IVVy with hand angular velocity (r = -0.40), and IVVz with the elbow angle range in the pull phase (r = - 0.37) (all p<0.05). This study shows the stability of the IVV (x,y,z), the inverse relation of the IVV (x, z) with v, the direct relation of the vmaxx and vminx with v, and the influence of the hand kinematics in the IVV.

Gross efficiency and energy expenditure in kayak ergometer exercise.

We purposed to study energy expenditure, power output and gross efficiency during kayak ergometer exercise in 12 elite sprint kayakers. 6 males (age 24.2±4.8 years, height 180.4±4.8 cm, body mass 79.7±8.5 kg) and 6 females (age 24.3±4.5 years, height 164.5±3.9 cm, body mass 65.4±3.5 kg), performed an incremental intermittent protocol on kayak ergometer with VO2 and blood lactate concentration assessment, a non-linear increase between power output and energy expenditure being observed. Paddling power output, energy expenditure and gross efficiency corresponding to VO2max averaged 199.92±50.41 W, 75.27±6.30 ml.kg - 1.min - 1, and 10.10±1.08%. Male kayakers presented higher VO2max, power output and gross efficiency at the VO2max, and lower heart rate and maximal lactate concentration than females, but no differences were found between genders regarding energy expenditure at VO2max. Aerobic and anaerobic components of energy expenditure evidenced a significant contribution of anaerobic energy sources in sprint kayak performance. Results also suggested the dependence of the gross efficiency on the changes in the amount of the aerobic and anaerobic contributions, at heavy and severe intensities. The inter-individual variance of the relationship between energy expenditure and the corresponding paddling power output revealed a relevant tracking for females (FDγ=0.73±0.06), conversely to the male group (FDγ=0.27±0.08), supporting that some male kayakers are more skilled in some paddling intensities than others.

Lifelong sedentary behaviour and femur structure.

The aim of the present study was to analyze the lifelong differences of femur structure in sedentary and physically active animal models. Thirty male C57BL/6 mice, 2 months old, were either: i) housed in cages with running wheel (AA; n=10), ii) housed in cages without running wheel (AS; n=10), iii) or sacrificed without intervention (Y; n=10). AA and AS animals were sacrificed after 23 months of housing. Right femur structure was analyzed in all animals by histomorphometry. Significant differences in several microarchitectural parameters of cancellous and cortical bone were identified between Y mice and both groups of aged mice, as well as between AA and AS groups. Lifelong physically active mice had significantly higher cancellous bone surface (Cn.BS) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) at both epiphyses when compared to AS animals. No differences were observed between Y and AA groups regarding osteocyte number (N.Ot) despite its significant reduction in AS animals, suggesting that age alone was not a cause for decreases in N.Ot. Our results suggest that the reduced bone quality observed in the elderly is not only a consequence of age but also of lack of physical activity since sedentary behaviour significantly aggravated the degenerative age-related bone differences.

Biomechanical analysis of backstroke swimming starts.

The relationships between the start time and kinematic, kinetic and electromyographic data were examined in order to establish the common features of an effective backstroke swimming start. Complementarily, different starting positions were analysed to identify the parameters that account for the fastest backstroke start time under different constraints. 6 high-level swimmers performed 4×15 m maximal trials of each start variants with different feet position: parallel and entirely submerged (BSFI) and above water surface (BSFE), being monitored with synchronized dual-media image, underwater platform plus handgrip with a load cell, and eletromyographic signal of RECTUS FEMORIS and GASTROCNEMIUS MEDIALIS. Mean and SD values of start time for BSFI and BSFE were 2.03 ± 0.19 and 2.14 ± 0.36 s, respectively. In both starts, high associations (r > =0.75, p < 0.001) were observed between start time and centre of mass resultant average velocity at glide phase and horizontal impulse at take-off for BSFI, and centre of mass horizontal position at the start signal for BSFE. It was concluded that the greater impulse during the take-off and its transformation into a fast underwater movement are determinant to decrease the start time at BSFI. Regarding BSFE, a greater centre of mass pool-wall approximation might imply a flatter take-off angle, compromising underwater velocity and starting performance.

VO2 kinetics in 200-m race-pace front crawl swimming.

Studies that aim to characterize oxygen uptake kinetics in efforts above maximal oxygen consumption intensity are scarce. Our aim was to analyze the oxygen kinetics in a maximal 200-m front crawl, all measurements being conducted in swimming pool conditions. 10 high-level male swimmers performed a maximal 200-m bout and oxygen uptake was directly measured through breath-by-breath gas analysis. Mean (±SD) peak oxygen uptake was 68.58 (±5.79) ml.kg(-1).min(-1), evidencing a fast component phase. As expected, peak oxygen uptake presented a direct relationship with mean swimming speed of the first 50-m lap and with the 200-m effort, and was also correlated with the amplitude of the fast component (r=0.75, r=0.72, r=0.73, p<0.05, respectively). The observed mean amplitude value was higher than those observed in the literature for other exercise intensity domains. However, the time for its onset, as well as the duration for attaining the steady state, was shorter, as the peak oxygen uptake was not correlated with these 2 components. Moreover, as previously described for swimming at high intensities, the slow component phenomenon was not observed. Aerobic metabolic pathway accounted for 78.6%, confirming the high aerobic contribution in middle distance swimming events.

Antibiotic prophylaxis for prevention of spontaneous bacterial peritonitis in liver cirrhosis: systematic review.

BACKGROUND AND AIM: Spontaneous bacterial peritonitis is a potentially life-threatening infection in patients with liver cirrhosis and ascites. Its prevention is vital to improve prognosis of cirrhotic patients. The main objective of this systematic review was to evaluate what is the most efficacious and safest antibiotic prophylactic strategy. METHODS: Studies were located by searching PubMed and Cochrane Central Register of Controlled Trials in The Cochrane Library until February 2019. Randomized controlled trials evaluating primary or secondary spontaneous bacterial peritonitis prophylaxis in cirrhotic patients with ascites were included. The selection of studies was performed in two stages: screening of titles and abstracts, and assessment of the full papers identified as relevant, considering the inclusion criteria. Data were extracted in a standardized way and synthesized qualitatively. RESULTS: Fourteen studies were included. This systematic review demonstrated that daily norfloxacin is effective as a prophylactic antibiotic for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis. Once weekly ciprofloxacin was not inferior to once daily norfloxacin, with good tolerance and no induced resistance. Trimethoprim-sulfamethoxazole and norfloxacin have similar efficacy for primary and secondary prophylaxis of spontaneous bacterial peritonitis, however, trimethoprim-sulfamethoxazole was associated with an increased risk of developing an adverse event. Rifaximin was more effective than norfloxacin in the secondary prophylaxis of spontaneous bacterial peritonitis, with a significant decrease in adverse events and mortality rate. CONCLUSIONS: Continuous long-term selective intestinal decontamination with norfloxacin is the most widely used prophylactic strategy in spontaneous bacterial peritonitis, yet other equally effective and safe options are available.

Enzyme functionalized microgels enable precise regulation of dissolved oxygen and anaerobe culture.

Anaerobes are a major constituent of the gut microbiome and profoundly influence the overall health of humans. However, the lack of a simple, cost-effective, and scalable system that mimics the anaerobic conditions of the human gut is hindering research on the gut microbiome and the development of therapeutics. Here, we address this gap by using glucose oxidase and catalase containing gelatin microparticles (GOx-CAT-GMPs) to precisely regulate dissolved oxygen concentration [O2] via GOx-mediated consumption of oxygen. Fluorescence images generated using conjugated polymer afterglow nanoparticles showed that [O2] can be tuned from 257.9 â€‹± â€‹6.2 to 0.0 â€‹± â€‹4.0 â€‹µM using GOx-CAT-GMPs. Moreover, when the obligate anaerobe Bacteroides thetaiotaomicron was inoculated in media containing GOx-CAT-GMPs, bacterial growth under ambient oxygen was comparable to control conditions in an anaerobic chamber (5.4 â€‹× â€‹105 and 8.8 â€‹× â€‹105 colony forming units mL-1, respectively). Finally, incorporating GOx-CAT-GMPs into a bioreactor that permitted continuous radial diffusion of oxygen and glucose generated a gut-mimetic [O2] gradient of 132.4 â€‹± â€‹2.6 â€‹µM in the outer ring of the reactor to 7.9 â€‹± â€‹1.7 â€‹µM at the core. Collectively, these results indicate that GOx-CAT-GMPs are highly effective oxygen-regulating materials. These materials can potentially be leveraged to advance gut microbiome research and fecal microbiota transplantation, particularly in low-resource settings.