Dynamics of Extensive Drug Resistance Evolution of Mycobacterium tuberculosis in a Single Patient During 9 Years of Disease and Treatment.

Mycobacterium tuberculosis is one of the hardest to treat bacterial pathogens with a high capacity to develop antibiotic resistance by mutations. Here we have performed whole-genome sequencing of consecutive M. tuberculosis isolates obtained during 9 years from a patient with pulmonary tuberculosis. The infecting strain was isoniazid resistant and during treatment it stepwise accumulated resistance mutations to 8 additional antibiotics. Heteroresistance was common and subpopulations with up to 3 different resistance mutations to the same drug coexisted. Sweeps of different resistant clones dominated the population at different time points, always coupled to resistance mutations coinciding with changes in the treatment regimens. Resistance mutations were predominant and no hitch-hiking, compensatory, or virulence-increasing mutations were detected, showing that the dominant selection pressure was antibiotic treatment. The results highlight the dynamic nature of M. tuberculosis infection, population structure, and resistance evolution and the importance of rapid antibiotic susceptibility tests to battle this pathogen.

Neural correlates of acoustic dissonance in music: The role of musicianship, schematic and veridical expectations.

In western music, harmonic expectations can be fulfilled or broken by unexpected chords. Musical irregularities in the absence of auditory deviance elicit well-studied neural responses (e.g. ERAN, P3, N5). These responses are sensitive to schematic expectations (induced by syntactic rules of chord succession) and veridical expectations about predictability (induced by experimental regularities). However, the cognitive and sensory contributions to these responses and their plasticity as a result of musical training remains under debate. In the present study, we explored whether the neural processing of pure acoustic violations is affected by schematic and veridical expectations. Moreover, we investigated whether these two factors interact with long-term musical training. In Experiment 1, we registered the ERPs elicited by dissonant clusters placed either at the middle or the ending position of chord cadences. In Experiment 2, we presented to the listeners with a high proportion of cadences ending in a dissonant chord. In both experiments, we compared the ERPs of musicians and non-musicians. Dissonant clusters elicited distinctive neural responses (an early negativity, the P3 and the N5). While the EN was not affected by syntactic rules, the P3a and P3b were larger for dissonant closures than for middle dissonant chords. Interestingly, these components were larger in musicians than in non-musicians, while the N5 was the opposite. Finally, the predictability of dissonant closures in our experiment did not modulate any of the ERPs. Our study suggests that, at early time windows, dissonance is processed based on acoustic deviance independently of syntactic rules. However, at longer latencies, listeners may be able to engage integration mechanisms and further processes of attentional and structural analysis dependent on musical hierarchies, which are enhanced in musicians.

Study of biorefineries based on experimental data: production of bioethanol, biogas, syngas, and electricity using coffee-cut stems as raw material.

Energy-driven biorefineries can be designed considering biotechnological and thermochemical conversion pathways. Nevertheless, energy and environmental comparisons are necessary to establish the best way to upgrade lignocellulosic biomass and set the requirements of these processes in different scenarios. This paper aims to evaluate experimentally a biorefinery producing energy vectors using coffee-cut stems (CCS) as feedstock. The obtained yields were the basis for energy and environmental analysis, in two different biorefinery scenarios: (i) production of bioethanol and biogas and (ii) production of syngas and electricity. The energy results indicated that the overall energy efficiency calculated in the first scenario was only 9.15%. Meanwhile, the second biorefinery configuration based on thermochemical routes presented an energy efficiency value of 70.89%. This difference was attributed to the higher consumption of utilities in the biorefinery based on biotechnological routes. The environmental results showed that the impact category of climate change for the first biorefinery (i.e., 0.0193 kg CO2 eq./MJ) had a lower value than that of the second process (i.e., 0.2377 kg CO2 eq./MJ). Thus, the biorefinery based on the biotechnological route presented a better environmental performance. Additionally, the results for both biorefineries allowed concluding that the inclusion of by-products and co-products in the calculation of the environmental analysis can dramatically affect the results.

New perspectives on person-centered care: an affordance-based account.

Despite the growing interest and supporting evidence for person-centered care (PCC), there is still a fundamental disagreement about what makes healthcare person-centered. In this article, we define PCC as operating with three fundamental conditions: personal, participatory and holistic. To further understand these concepts, we develop a framework based on the theory of affordances, which we apply to the healthcare case of rehabilitation and a concrete experiment on social interactions between persons with cerebral palsy and physio- and occupational therapists. Based on the application of the theory, we argue that in order for healthcare to be considered as PCC, professionals need to adopt a personalistic attitude in their care, defined (at the how-level) in terms of mutual affordances: how the professional and the person of care acknowledges each other as a person in an interaction. In opposition, we define (at the what level) the functionalistic attitude in terms of object affordances, those related to a concrete goal. We show that PCC requires a balance of personalistic and functionalistic attitudes, since this contributes to a participatory and holistic conception of, and interaction with, the person of care.

Ternary meter from spatial sounds: Differences in neural entrainment between musicians and non-musicians.

The present study explores the relationship between the rhythmic structure of music and the spatial dimension of sound. We study how the brain interacts with spatially-separated sounds to build up a metrical structure. Participants listened to sequences of isochronous sounds that came from different positions on the azimuth plane: 0° (control condition), ±30°, ±60° or ±90° (spatial conditions). Ternary meter was signaled by the alternation of one sound on one side and two sounds on the symmetrical side. In Experiment 1, musicians and non-musicians paid attention to the spatial sounds. In Experiment 2, participants paid attention to a visual distractor. We recorded their electroencephalograms and performed frequency-tagging analyses. In both experiments, the isochronous beat elicited steady-state evoked-potentials at the frequency of the beat (2.4 Hz). While in Experiment 1 the alternation produced clear responses at the frequency of the ternary meter (0.8 Hz), in Experiment 2 these responses were only significant in the Spatial 90° condition, and mainly in musicians. This suggests that top-down attentional mechanisms are in play for meter induction. Besides, musicians showed stronger responses to beat and meter than non-musicians, suggesting that formal musical training enhances the neural entrainment to spatially-defined rhythms.

Potent Vasodilator and Cellular Antioxidant Activity of Endemic Patagonian Calafate Berries (Berberis microphylla) with Nutraceutical Potential.

Hydroalcoholic extracts of Patagonian Calafate berry (Berberis microphylla) contain mono or disaccharide conjugated anthocyanins and flavonols. The Liquid Chromatography-Mass Spectrometry (LC-MS) chemical extract profile identified glycosylated anthocyanidins such as delphinidin-, petunidin- and malvidin-3-glucoside as the major constituents. The predominant flavonols were 3-O substituents quercetin-rutinoside or -rhamnoside. Anthocyanins doubled flavonols in mass (13.1 vs. 6 mg/g extract). Polyphenols vascular actions were examined in the rat arterial mesenteric bed bioassay; extract perfusion elicited concentration-dependent vasodilatation mimicked by conjugated anthocyanins standards. Vascular responses of main glycosylated anthocyanins were endothelium-dependent (p < 0.001) and mediated by NO production (p < 0.05). The anthocyanins antioxidant activity determined in isolated endothelial cells (CAA) showed a reduced redox potential as compared to the extract or quercetin. While in the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, the anthocyanins showed an equivalent quercetin potency, the extract was 15-fold less active, proposing that the anthocyanin-induced vasodilation is not due to an antioxidant mechanism. The extract shows promising commercial nutraceutical potential.

Early neural responses underlie advantages for consonance over dissonance.

Consonant musical intervals tend to be more readily processed than dissonant intervals. In the present study, we explore the neural basis for this difference by registering how the brain responds after changes in consonance and dissonance, and how formal musical training modulates these responses. Event-related brain potentials (ERPs) were registered while participants were presented with sequences of consonant intervals interrupted by a dissonant interval, or sequences of dissonant intervals interrupted by a consonant interval. Participants were musicians and non-musicians. Our results show that brain responses triggered by changes in a consonant context differ from those triggered in a dissonant context. Changes in a sequence of consonant intervals are rapidly processed independently of musical expertise, as revealed by a change-related mismatch negativity (MMN, a component of the ERPs triggered by an odd stimulus in a sequence of stimuli) elicited in both musicians and non-musicians. In contrast, changes in a sequence of dissonant intervals elicited a late MMN only in participants with prolonged musical training. These different neural responses might form the basis for the processing advantages observed for consonance over dissonance and provide information about how formal musical training modulates them.

Time course and functional neuroanatomy of speech segmentation in adults.

The present investigation was devoted to unraveling the time-course and brain regions involved in speech segmentation, which is one of the first processes necessary for learning a new language in adults and infants. A specific brain electrical pattern resembling the N400 language component was identified as an indicator of speech segmentation of candidate words. This N400 trace was clearly elicited after a short exposure to the words of the new language and showed a decrease in amplitude with longer exposure. Two brain regions were observed to be active during this process: the posterior superior temporal gyrus and the superior part of the ventral premotor cortex. We interpret these findings as evidence for the existence of an auditory-motor interface that is responsible for isolating possible candidate words when learning a new language in adults.

Contribución del neuropéptido Y a la fisiología de la co-transmisión simpática humana: estudios en biopsias de vena safena / Neuropeptide Y contribution to the physiology of human sympathetic cotransmission: studies in saphenous vein biopsies

Background: It is known that the sympathetic varicosities co-store and co-release norepinephrine (NE) together with adenosine S-triphosphate (ATP) and neuropeptide Y (NPY). Aim: To describe the chemical characterisation of stored and released NPY from the varicosities of sympathetic nerve terminals surrounding segments of the human saphenous vein, and the vasomotor activity of rings electrically depolarized or contracted by the exogenous application of the co-transmitters. Material and methods: Saphenous vein tissues were obtained from patients undergoing elective cardiac revascularization surgery. Results: The chromatographic profile of NPY extracted from biopsies is identical to a chemical standard of human NPY. Upon electrical depolarisation of the perivascular sympathetic nerve terminals, we demonstrated the release of NPY to the superfusion media, which did not exceed a 1percent of its stored content. The release of the peptide is sensitive to guanethidine, and to extracellular calcium, suggesting that the mechanism of its release is exocytotic in nature. The electrically evoked release of NPY is dependent on the frequency and duration of the electrical pulses. Phenoxybenzamine reduces the electrically evoked release of NPY. Exogenous application of NE and ATP contract saphenous vein rings; the simultaneous application of NE plus ATP causes a synergic response, effect which is further potentiated by the joint co-application of 10 nM NPY. Conclusions: Present results highlight the role of NPY as a sympathetic co-transmitter in the regulation of human vascular tone