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).

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.

Functional tests associated with sarcopenia in moderate chronic obstructive pulmonary disease.

Objectives: To evaluate the association of physical and functional measures with sarcopenia in moderate chronic obstructive pulmonary disease (COPD) and to establish cutoff points for sarcopenia screening.Methods: The study included COPD with and without sarcopenia, of both sexes who were over 50 years old. Participants were assessed for lung function, body composition, grip strength, Short Physical Performance Battery (SPPB), 5-repetition, 10-repetition and 30-s sit-to-stand tests (5STS, 10STS, and 30STS, respectively). In addition, 6-min walking test, respiratory muscular strength, and physical activity level were tested.Results: The study had 35 participants, 24 men (68.6%) and moderate COPD (51.4%). COPD-sarcopenia showed lower values in lean mass, body fat and body mass alongside lower performance in 10 and 30 STS tests, SPPB and gait speed compared to non-sarcopenic group. The cutoff points with better sensitivity and specificity to identify sarcopenia were 10.88 and 34.14 s, 15 repetitions, and 10 points in the 5STS, 10STS, 30STS, and SPPB, respectively. The comparison of the receiver operating curves evidenced no differences between the functional tests. Only 30STS and SPPB showed acceptable discriminatory power.Conclusion: Functional tests, especially 30STS and SPPB, are simple and affordable tools for screening sarcopenia in COPD with moderate obstruction.

Does whole body vibration exercise improve oxidative stress markers in women with fibromyalgia?

The objective of this study was to investigate the effect of whole body vibration (WBV) exercise on oxidative stress markers in a group of women with fibromyalgia (FM) compared to a group of healthy women (CT). Twenty-one women diagnosed with FM and 21 age- and weight-matched healthy women were enrolled the study. Plasma oxidative stress markers (primary outcomes) were evaluated at rest and after WBV, and included thiobarbituric acid reactive substances (TBARS), iron reduction capacity (FRAP), superoxide dismutase antioxidant enzymes activity (SOD), and catalase (CAT). At rest, the FM group had higher TBARS (P<0.001) and FRAP (P<0.001), and lower CAT (P=0.005) compared to the CT. In the CT group, the WBV had no effect on TBARS (P=0.559) and FRAP (P=0.926), whereas it increased both SOD (P<0.001) and CAT (P<0.001). In the FM group, the WBV reduced TBARS (p <0.001), FRAP (P<0.001), and CAT (P=0.005), while it increased SOD (P=0.019). There was an interaction effect (moments vs groups) in the TBARS (effect size=1.34), FRAP (effect size=0.93), CAT (effect size=1.45), and SOD (effect size=1.44) (P<0.001). A single trial of WBV exercise improved all oxidant and antioxidant parameters towards a greater adaptation to the stress response in FM women.

Does whole body vibration exercise improve oxidative stress markers in women with fibromyalgia?

The objective of this study was to investigate the effect of whole body vibration (WBV) exercise on oxidative stress markers in a group of women with fibromyalgia (FM) compared to a group of healthy women (CT). Twenty-one women diagnosed with FM and 21 age- and weight-matched healthy women were enrolled the study. Plasma oxidative stress markers (primary outcomes) were evaluated at rest and after WBV, and included thiobarbituric acid reactive substances (TBARS), iron reduction capacity (FRAP), superoxide dismutase antioxidant enzymes activity (SOD), and catalase (CAT). At rest, the FM group had higher TBARS (P<0.001) and FRAP (P<0.001), and lower CAT (P=0.005) compared to the CT. In the CT group, the WBV had no effect on TBARS (P=0.559) and FRAP (P=0.926), whereas it increased both SOD (P<0.001) and CAT (P<0.001). In the FM group, the WBV reduced TBARS (p <0.001), FRAP (P<0.001), and CAT (P=0.005), while it increased SOD (P=0.019). There was an interaction effect (moments vs groups) in the TBARS (effect size=1.34), FRAP (effect size=0.93), CAT (effect size=1.45), and SOD (effect size=1.44) (P<0.001). A single trial of WBV exercise improved all oxidant and antioxidant parameters towards a greater adaptation to the stress response in FM women.

Detection and Molecular Characterization of Yellow Fever Virus, 2017, Brazil.

At the end of 2016, Brazil experienced an unprecedented yellow fever (YF) outbreak. Clinical, molecular and ecological aspects of human and non-human primate (NHP) samples collected at the beginning of the outbreak are described in this study. Spatial distribution analyses demonstrated a strong overlap between human and NHP cases. Through molecular analyses, we showed that the outbreak had a sylvatic origin, caused by the South American genotype 1 YFV, which has already been shown to circulate in Brazil. As expected, the clusters of cases were identified in regions with a low vaccination coverage. Our findings highlight the importance of the synchronization of animal surveillance and health services to identify emerging YF cases, thereby promoting a better response to the vulnerable population.

Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

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.

Detection of Vaccinia virus during an outbreak of exanthemous oral lesions in Brazilian equids.

REASONS FOR PERFORMING STUDY: In August 2014, an outbreak of oral exanthematous disease in equids was reported in Brazil, affecting 11 donkeys and 3 mules. OBJECTIVES: To investigate if Vaccinia virus (VACV) was the aetiological agent in this outbreak. STUDY DESIGN: Investigation of clinical cases using serological, molecular and phylogenetic approaches. METHODS: To analyse the presence of neutralising antibodies against VACV, samples were submitted in triplicate to a plaque-reduction neutralisation test (PRNT50% ). On the basis of previous studies which detected VACV DNA in sera, we submitted extracted DNA samples to different polymerase chain reaction (PCR) platforms targeting Orthopoxvirus (OPV) genes (C11R, A56R and A26L). The PCR products were directly sequenced in both orientations using specific primers and capillary electrophoresis. The alignment and phylogenetic analysis of the A26L and A56R nucleotide sequences (maximum likelihood) were prepared with the obtained nucleotide fragments. RESULTS: Serological and molecular data suggested VACV as the aetiological agent. The neutralising antibodies against OPV were detected in 5 (55.5%) of the equids, with titres ≥40 neutralising u/ml. Based on the results obtained from all PCR platforms, all samples were positive for OPV: 9 (100%) for A56R, 4 (44.4%) for C11R and 3 (33.3%) for A26L. The alignment of the nucleotide sequences of the A26L and A56R fragments revealed that the samples were highly similar to the homologous genes from other Brazilian VACV Group 1 isolates (98.8% identity on average). Furthermore, both the A26L and A56R sequences showed signature deletions also present in the sequences of Group 1 VACV isolates from Brazil. CONCLUSIONS: Our data raises questions about the role of equids in the chain of VACV epidemiology. The surveillance of equids in VACV-affected areas worldwide is relevant.

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.

Behavioural variability and motor performance: Effect of practice specialization in front crawl swimming.

The aim was to examine behavioural variability within and between individuals, especially in a swimming task, to explore how swimmers with various specialty (competitive short distance swimming vs. triathlon) adapt to repetitive events of sub-maximal intensity, controlled in speed but of various distances. Five swimmers and five triathletes randomly performed three variants (with steps of 200, 300 and 400m distances) of a front crawl incremental step test until exhaustion. Multi-camera system was used to collect and analyse eight kinematical and swimming efficiency parameters. Analysis of variance showed significant differences between swimmers and triathletes, with significant individual effect. Cluster analysis put these parameters together to investigate whether each individual used the same pattern(s) and one or several patterns to achieve the task goal. Results exhibited ten patterns for the whole population, with only two behavioural patterns shared between swimmers and triathletes. Swimmers tended to use higher hand velocity and index of coordination than triathletes. Mono-stability occurred in swimmers whatever the task constraint showing high stability, while triathletes revealed bi-stability because they switched to another pattern at mid-distance of the task. Finally, our analysis helped to explain and understand effect of specialty and more broadly individual adaptation to task constraint.

Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers.

Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100% agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.

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.

Stochastic dynamic causal modelling of FMRI data with multiple-model Kalman filters.

INTRODUCTION: This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Neural Signals and Images". BACKGROUND: Dynamic Causal Modelling (DCM) is a generic formalism to study effective brain connectivity based on neuroimaging data, particularly functional Magnetic Resonance Imaging (fMRI). Recently, there have been attempts at modifying this model to allow for stochastic disturbances in the states of the model. OBJECTIVES: This paper proposes the Multiple-Model Kalman Filtering (MMKF) technique as a stochastic identification model discriminating among different hypothetical connectivity structures in the DCM framework; moreover, the performance compared to a similar deterministic identification model is assessed. METHODS: The integration of the stochastic DCM equations is first presented, and a MMKF algorithm is then developed to perform model selection based on these equations. Monte Carlo simulations are performed in order to investigate the ability of MMKF to distinguish between different connectivity structures and to estimate hidden states under both deterministic and stochastic DCM. RESULTS: The simulations show that the proposed MMKF algorithm was able to successfully select the correct connectivity model structure from a set of pre-specified plausible alternatives. Moreover, the stochastic approach by MMKF was more effective compared to its deterministic counterpart, both in the selection of the correct connectivity structure and in the estimation of the hidden states. CONCLUSIONS: These results demonstrate the applicability of a MMKF approach to the study of effective brain connectivity using DCM, particularly when a stochastic formulation is desirable.

Autonomic adaptation after traditional and reverse swimming training periodizations.

The objective of the present study was to analyze the autonomic response of trained swimmers to traditional and reverse training periodization models. Seventeen swimmers were divided in two groups, performing a traditional periodization (TPG) or a reverse periodization (RPG) during a period of 10 weeks. Heart rate variability and 50 m swimming performance were analyzed before and after the training programs. After training, the TPG decreased the values of the high frequency band (HF), the number of differences between adjacent normal R-R intervals longer than 50 ms (NN50) and the percentage of differences between adjacent normal R-R intervals more than 50 ms (pNN50), and the RPG increased the values of HF and square root of the mean of the sum of the squared differences between adjacent normal R-R intervals (RMSSD). None of the groups improved significantly their performance in the 50-m test. The autonomic response of swimmers was different depending on the periodization performed, with the reverse periodization model leading to higher autonomic adaption. Complementary, the data suggests that autonomic adaptations were not critical for the 50-m swimming performance.

Pamidronate affects the mandibular cortex of children with osteogenesis imperfecta.

We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI.