Heart Rate Variability to Automatically Identify Hyperbaric States Considering Respiratory Component.

This study's primary objective was to identify individuals whose physiological responses deviated from the rest of the study population by automatically monitoring atmospheric pressure levels to which they are exposed and using parameters derived from their heart rate variability (HRV). To achieve this, 28 volunteers were placed in a dry hyperbaric chamber, where they experienced varying pressures from 1 to 5 atmospheres, with five sequential stops lasting five minutes each at different atmospheric pressures. The HRV was dissected into two components: the respiratory component, which is linked to respiration; and the residual component, which is influenced by factors beyond respiration. Nine parameters were assessed, including the respiratory rate, four classic HRV temporal parameters, and four frequency parameters. A k-nearest neighbors classifier based on cosine distance successfully identified the atmospheric pressures to which the subjects were exposed to. The classifier achieved an 88.5% accuracy rate in distinguishing between the 5 atm and 3 atm stages using only four features: respiratory rate, heart rate, and two frequency parameters associated with the subjects' sympathetic responses. Furthermore, the study identified 6 out of 28 subjects as having atypical responses across all pressure levels when compared to the majority. Interestingly, two of these subjects stood out in terms of gender and having less prior diving experience, but they still exhibited normal responses to immersion. This suggests the potential for establishing distinct safety protocols for divers based on their previous experience and gender.

Enhancing Safety in Hyperbaric Environments through Analysis of Autonomic Nervous System Responses: A Comparison of Dry and Humid Conditions.

Diving can have significant cardiovascular effects on the human body and increase the risk of developing cardiac health issues. This study aimed to investigate the autonomic nervous system (ANS) responses of healthy individuals during simulated dives in hyperbaric chambers and explore the effects of the humid environment on these responses. Electrocardiographic- and heart-rate-variability (HRV)-derived indices were analyzed, and their statistical ranges were compared at different depths during simulated immersions under dry and humid conditions. The results showed that humidity significantly affected the ANS responses of the subjects, leading to reduced parasympathetic activity and increased sympathetic dominance. The power of the high-frequency band of the HRV after removing the influence of respiration, PHF⟂¯, and the number of pairs of successive normal-to-normal intervals that differ by more than 50 ms divided by the total number of normal-to-normal intervals, pNN50¯, indices were found to be the most informative in distinguishing the ANS responses of subjects between the two datasets. Additionally, the statistical ranges of the HRV indices were calculated, and the classification of subjects as "normal" or "abnormal" was determined based on these ranges. The results showed that the ranges were effective at identifying abnormal ANS responses, indicating the potential use of these ranges as a reference for monitoring the activity of divers and avoiding future immersions if many indices are out of the normal ranges. The bagging method was also used to include some variability in the datasets' ranges, and the classification results showed that the ranges computed without proper bagging represent reality and its associated variability. Overall, this study provides valuable insights into the ANS responses of healthy individuals during simulated dives in hyperbaric chambers and the effects of humidity on these responses.

Impact of Physical Activity and Exercise on the Epigenome in Skeletal Muscle and Effects on Systemic Metabolism.

Exercise and physical activity induces physiological responses in organisms, and adaptations in skeletal muscle, which is beneficial for maintaining health and preventing and/or treating most chronic diseases. These adaptations are mainly instigated by transcriptional responses that ensue in reaction to each individual exercise, either resistance or endurance. Consequently, changes in key metabolic, regulatory, and myogenic genes in skeletal muscle occur as both an early and late response to exercise, and these epigenetic modifications, which are influenced by environmental and genetic factors, trigger those alterations in the transcriptional responses. DNA methylation and histone modifications are the most significant epigenetic changes described in gene transcription, linked to the skeletal muscle transcriptional response to exercise, and mediating the exercise adaptations. Nevertheless, other alterations in the epigenetics markers, such as epitranscriptomics, modifications mediated by miRNAs, and lactylation as a novel epigenetic modification, are emerging as key events for gene transcription. Here, we provide an overview and update of the impact of exercise on epigenetic modifications, including the well-described DNA methylations and histone modifications, and the emerging modifications in the skeletal muscle. In addition, we describe the effects of exercise on epigenetic markers in other metabolic tissues; also, we provide information about how systemic metabolism or its metabolites influence epigenetic modifications in the skeletal muscle.

Heart Failure With Preserved Ejection Fraction: A Comprehensive Review and Update of Diagnosis, Pathophysiology, Treatment, and Perioperative Implications.

Almost three-quarters of all heart failure patients who are older than 65 have heart failure with preserved ejection fraction (HFpEF). The proportion and hospitalization rate of patients with HFpEF are increasing steadily relative to patients in whom heart failure occurs as result of reduced ejection fraction. The predominance of the HFpEF phenotype most likely is explained by the prevalence of medical conditions associated with an aging population. A multitude of age-related, medical, and lifestyle risk factors for HFpEF have been identified as potential causes for the sustained low-grade proinflammatory state that accelerates disease progression. Profound left ventricular (LV) systolic and diastolic stiffening, elevated LV filling pressures, reduced arterial compliance, left atrial hypertension, pulmonary venous congestion, and microvascular dysfunction characterize HFpEF, but pulmonary arterial hypertension, right ventricular dilation and dysfunction, and atrial fibrillation also frequently occur. These cardiovascular features make patients with HFpEF exquisitely sensitive to the development of hypotension in response to acute declines in LV preload or afterload that may occur during or after surgery. With the exception of symptom mitigation, lifestyle modifications, and rigorous control of comorbid conditions, few long-term treatment options exist for these unfortunate individuals. Patients with HFpEF present for surgery on a regular basis, and anesthesiologists need to be familiar with this heterogeneous and complex clinical syndrome to provide successful care. In this article, the authors review the diagnosis, pathophysiology, and treatment of HFpEF and also discuss its perioperative implications.

Photoplethysmographic Waveform and Pulse Rate Variability Analysis in Hyperbaric Environments.

The main aim of this work is to identify alterations in the morphology of the pulse photoplethysmogram (PPG) signal, due to the exposure of the subjects to a hyperbaric environment. Additionally, their Pulse Rate Variability (PRV) is analysed to characterise the response of their Autonomic Nervous System (ANS). To do that, 28 volunteers are introduced into a hyperbaric chamber and five sequential stages with different atmospheric pressures from 1 atm to 5 atm are performed. In this work, nineteen morphological parameters of the PPG signal are analysed: the pulse amplitude; eight parameters related to pulse width; eight parameters related to pulse area; and the two two pulse slopes. Also, classical time and frequency parameters of PRV are computed. Notable widening of the pulses width is observed in the stages analysed. The PPG area increases with pressure, with no significant changes when the initial pressure is recovered. These changes in PPG waveform may be caused by an increase in the systemic vascular resistance as a consequence of of vasoconstriction in the extremities, suggesting a sympathetic activation. However, the PRV results show an augmented parasympathetic activity and a reduction in the parameters that characterise the sympathetic response. So, only a sympathetic activation is detected in the peripheral region, as reflected by PPG morphology. The information regarding the ANS and the cardiovascular response that can be extracted from the PPG signal, as well as its compatibility with wet conditions make this signal the most suitable for studying the physiological response in hyperbaric environments.

Determining the impact of uncharacterized inversions in the human genome by droplet digital PCR.

Despite the interest in characterizing genomic variation, the presence of large repeats at the breakpoints hinders the analysis of many structural variants. This is especially problematic for inversions, since there is typically no gain or loss of DNA. Here, we tested novel linkage-based droplet digital PCR (ddPCR) assays to study 20 inversions ranging from 3.1 to 742 kb flanked by inverted repeats (IRs) up to 134 kb long. Of those, we validated 13 inversions predicted by different genome-wide techniques. In addition, we obtained new experimental human population information across 95 African, European, and East Asian individuals for 16 inversions, including four already validated variants without high-throughput genotyping methods. Through comparison with previous data, independent replicates and both inversion breakpoints, we demonstrate that the technique is highly accurate and reproducible. Most studied inversions are widespread across continents, and their frequency is negatively correlated with genetic length. Moreover, all except two show clear signs of being recurrent, and we could better define the factors affecting recurrence levels and estimate the inversion rate across the genome. Finally, the generated genotypes have allowed us to check inversion functional effects, validating gene expression differences reported before for two inversions and finding new candidate associations. Therefore, the developed methodology makes it possible to screen these and other complex genomic variants quickly in a large number of samples for the first time, highlighting the importance of direct genotyping to assess their potential consequences and clinical implications.

Characteristics associated with Publication of Randomized Controlled Trials in the Journal of Cardiothoracic and Vascular Anesthesia: A 15-Year Analysis, 2004-2018.

Randomized controlled trials (RCTs) provide important data to guide clinical decisions. Publication bias may limit the applicability of RCTs because many clinical investigators prefer to submit and journals more selectively accept studies with positive results. The authors tested the hypothesis that positive RCTs published in the Journal of Cardiothoracic and Vascular Anesthesia were more likely to be associated with factors known to predict publication of positive versus negative RCTs in other journals. This observational study was an internet analysis of all issues of Journal of Cardiothoracic and Vascular Anesthesia from 2004-2018. Each issue was searched to identify human RCTs. The numbers of centers and enrolled patients in each RCT were tabulated. The corresponding author determined the country of origin (United States v international). A trial was "positive" or "negative" based on rejection or confirmation of the null hypothesis, respectively, for the primary outcome variable or the majority of measured outcomes if a primary outcome was not identified. The presence or absence of a hypothesis, randomization methodology, sample size calculation, and blinded research design was recorded. Registration in a public database, Consolidated Statements of Reporting Trials (CONSORT) guideline compliance, and the source of funding also were determined. The number of citations for each RCT was determined by using Google Scholar; the citation rate was calculated as the ratio of the number of total citations and the duration in years since the trial's original publication. A total of 296 RCTs were identified, of which 58.8% reported positive results. Most RCTs were single center, relatively small, and international in origin. Total citations/RCT decreased over time, but citations/year did not. The percentage of RCTs that identified a randomization method, were registered, or followed CONSORT guidelines increased in a time-dependent manner. No differences in any factors associated with publication of RCTs were observed when positive and negative trials were compared. The Journal of Cardiothoracic and Vascular Anesthesia publishes more positive than negative RCTs, but factors that have been previously associated with RCT publication in other journals were similar between groups.

Teorías bioéticas, protección de la vida y ley natural / Bioethics theories, the protection of life and natural law

La bioética principialista de Beauchamp y Childress se ha hecho con un lugar preeminente en la Bioética actual. No obstante, presenta algunas carencias teóricas importantes: falta de elaboración de algunos conceptos, tendencia al relativismo moral, etc. Entre los múltiples posicionamientos éticos alternativos actuales desde los cuales cubrir tales carencias, pensamos que el más adecuado es la teoría de la ley natural. Esta ofrece una reflexión argumentada sobre el bien y los bienes humanos y sobre su relación con los principios morales generales. Desde tales bienes, dicha teoría sostiene la existencia de acciones que son siempre maleficentes, esto es, acciones intrínsecamente y universalmente malas. El artículo aplica la teoría de la ley natural a temas relacionados con la protección de la vida humana (aborto, eutanasia, legítima defensa y manipulación genética)

Principlist Bioethics by Beauchamp and Childress has reached a prominent status in contemporary Bioethics. Nevertheless, it includes some important theoretical problems: some lacks when defining some concepts, a tendency to ethical relativism, etc. Among the ethical alternative approaches from which such problems can be solved, we think that the most appropiate is the Natural Law theory. It offers a reasoned reflection on the concept of good and on human basic goods and their relation with moral general principles. From such goods, this ethical theory supports the existence of actions that are always maleficent acts, that is, intrinsically and universally evil acts. The article applies the Natural Law theory to issues related to the protection of human life (abortion, euthanasia, self-defense and genetic manipulation)

[Bioethics theories, the protection of life and natural law]. / Teorías bioéticas, protección de la vida y ley natural.

Principlist Bioethics by Beauchamp and Childress has reached a prominent status in contemporary Bioethics. Nevertheless, it includes some important theoretical problems: some lacks when defining some concepts, a tendency to ethical relativism, etc. Among the ethical alternative approaches from which such problems can be solved, we think that the most appropiate is the Natural Law theory. It offers a reasoned reflection on the concept of good and on human basic goods and their relation with moral general principles. From such goods, this ethical theory supports the existence of actions that are always maleficent acts, that is, intrinsically and universally evil acts. The article applies the Natural Law theory to issues related to the protection of human life (abortion, euthanasia, self-defense and genetic manipulation)..

Evolutionary and functional impact of common polymorphic inversions in the human genome.

Inversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about polymorphic inversions in the human genome due to the difficulty of their detection. Here, we develop a new high-throughput genotyping method based on probe hybridization and amplification, and we perform a complete study of 45 common human inversions of 0.1-415 kb. Most inversions promoted by homologous recombination occur recurrently in humans and great apes and they are not tagged by SNPs. Furthermore, there is an enrichment of inversions showing signatures of positive or balancing selection, diverse functional effects, such as gene disruption and gene-expression changes, or association with phenotypic traits. Therefore, our results indicate that the genome is more dynamic than previously thought and that human inversions have important functional and evolutionary consequences, making possible to determine for the first time their contribution to complex traits.

Photoplethysmographic Waveform in Hyperbaric Environment.

The objective of this work is the identification of significant variations of morphological parameters of the photoplethysmographic (PPG) signal when the subjects are exposed to an increase in atmospheric pressure. To achieve this goal, the PPG signal of 26 subjects, exposed to a hyperbaric environment whose pressure increases up to 5 atm, has been recorded. From this record, segments of 4 minutes have been processed at 1 atm, 3 atm and 5 atm, both in the descending (D) and ascending (A) periods of the immersion. In total, four states (3D, 5, 3A and 1A) normalized to the basal state (1D) have been considered. In these segments, six morphological parameters of the PPG signal were studied. The width, the amplitude, the widths of the anacrotic and catacrotic phases, and the upward and downward slopes of each PPG pulse were extracted. The results showed significant increases in the three parameters related to the pulse width. This increase is significant in the four states analysed for the anacrotic phase width. Furthermore, a significant decrease in the amplitude and in both slopes (in the states 1A) was observed. These results show that the PPG width responds rapidly to the increase in pressure, indicating an activation of the sympathetic system, while amplitude and pulse slopes are decreased when the subjects are exposed to the hyperbaric environment for a considerable period of time.

Autonomic Nervous System Measurement in Hyperbaric Environments Using ECG and PPG Signals.

The main aim of this paper was to characterize the Autonomic Nervous System response in hyperbaric environments using electrocardiogram (ECG) and pulse-photoplethysmogram (PPG) signals. To that end, 26 subjects were introduced into a hyperbaric chamber and five stages with different atmospheric pressures (1 atm; descent to 3 and 5 atm; ascent to 3 and 1 atm) were recorded. Respiratory information was extracted from the ECG and PPG signals and a combined respiratory rate was studied. This information was also used to analyze Heart Rate Variability (HRV) and Pulse Rate Variability (PRV). The database was cleaned by eliminating those cases where the respiratory rate dropped into the low frequency band (LF: 0.04-0.15 Hz) and those in which there was a discrepancy between the respiratory rates estimated using the ECG and PPG signals. Classical temporal and frequency indices were calculated in such cases. The ECG results showed a time-related dependency, with the heart rate and sympathetic markers (normalized power in LF and LF/HF ratio) decreasing as more time was spent inside the hyperbaric environment. A dependence between the atmospheric pressure and the parasympathetic response, as reflected in the high-frequency band power (HF: 0.15-0.40 Hz), was also found, with power increasing with atmospheric pressure. The combined respiratory rate also reached a maximum in the deepest stage; thus, highlighting a significant difference between this stage and the first one. The PPG data gave similar findings and also allowed the oxygen saturation to be computed; therefore, we propose the use of this signal for future studies in hyperbaric environments.

Chirp-based direct phase modulation of VCSELs for cost-effective transceivers.

A 2.5 Gb/s differential binary phase-shift keying (DPSK) transmitter based on direct phase modulation of a vertical cavity surface emitting lasers (VCSEL) using its own chirp is proposed. The VCSEL, which has a wavelength of 1539.84 nm, has been characterized both statically and dynamically. The sensitivity of a single photodiode heterodyne receiver using the proposed 2.5 Gb/s VCSEL transmitter is -39.5 dBm. Thus, this transmitter is an extremely cost-effective solution for future access networks.

Detailed analysis of inversions predicted between two human genomes: errors, real polymorphisms, and their origin and population distribution.

The growing catalogue of structural variants in humans often overlooks inversions as one of the most difficult types of variation to study, even though they affect phenotypic traits in diverse organisms. Here, we have analysed in detail 90 inversions predicted from the comparison of two independently assembled human genomes: the reference genome (NCBI36/HG18) and HuRef. Surprisingly, we found that two thirds of these predictions (62) represent errors either in assembly comparison or in one of the assemblies, including 27 misassembled regions in HG18. Next, we validated 22 of the remaining 28 potential polymorphic inversions using different PCR techniques and characterized their breakpoints and ancestral state. In addition, we determined experimentally the derived allele frequency in Europeans for 17 inversions (DAF = 0.01-0.80), as well as the distribution in 14 worldwide populations for 12 of them based on the 1000 Genomes Project data. Among the validated inversions, nine have inverted repeats (IRs) at their breakpoints, and two show nucleotide variation patterns consistent with a recurrent origin. Conversely, inversions without IRs have a unique origin and almost all of them show deletions or insertions at the breakpoints in the derived allele mediated by microhomology sequences, which highlights the importance of mechanisms like FoSTeS/MMBIR in the generation of complex rearrangements in the human genome. Finally, we found several inversions located within genes and at least one candidate to be positively selected in Africa. Thus, our study emphasizes the importance of careful analysis and validation of large-scale genomic predictions to extract reliable biological conclusions.

Low cost and compact analytical microsystem for carbon dioxide determination in production processes of wine and beer.

The design, construction and evaluation of a low cost, cyclic olefin copolymer (COC)-based continuous flow microanalyzer, with optical detection, to monitor carbon dioxide in bottled wines and beers as well as in fermentation processes, is presented. The microsystem, constructed by computer numerically controlled (CNC) micromilling and using a multilayer approach, integrates microfluidics, gas-diffusion module and an optical flow-cell in a single polymeric substrate. Its size is slightly bigger than a credit card, exactly 45 × 60 × 4 mm in the microfluidic and diffusion module zone and 22.5 × 40 × 3 mm in the flow-cell zone. The gas-diffusion module is based on a hydrophobic polyvinylidene fluoride (PVDF) membrane, which allows the transfer of the carbon dioxide present in the sample to a bromothymol blue (BTB) pH-sensitive acceptor solution, where the color change is measured optically. The detection system consisted of a LED with an emission peak at 607 nm and a photodiode integrated in a printed circuit board (PCB). The obtained analytical features after the optimization of the microfluidic platform and hydrodynamic variables are a linear range from 255 to 10000 mg L(-1) of CO2 and a detection limit of 83 mg L(-1) with a sampling rate of 30 samples h(-1).

1 Gbps full-duplex links for ultra-dense-WDM 6.25 GHz frequency slots in optical metro-access networks.

1 Gbps full-duplex optical links for 6.25 GHz ultra dense WDM frequency slots are demonstrated and optimized for cost-effective metro-access networks. The OLT-ONU downlinks are based on 1 Gbps Nyquist-DPSK using MZM and single-detector heterodyne reception obtaining a sensitivity of -52 dBm. The ONU-OLT uplinks are based on 1 Gbps NRZ-DPSK by directly phase modulated DFB and also single-detector heterodyne reception obtaining same sensitivity of -52 dBm. The power budget of full-duplex link is 43 dB. These proposed links can provide service to 16 (32) users at each 100 (200) GHz WDM channel.

Functional Impact and Evolution of a Novel Human Polymorphic Inversion That Disrupts a Gene and Creates a Fusion Transcript.

Despite many years of study into inversions, very little is known about their functional consequences, especially in humans. A common hypothesis is that the selective value of inversions stems in part from their effects on nearby genes, although evidence of this in natural populations is almost nonexistent. Here we present a global analysis of a new 415-kb polymorphic inversion that is among the longest ones found in humans and is the first with clear position effects. This inversion is located in chromosome 19 and has been generated by non-homologous end joining between blocks of transposable elements with low identity. PCR genotyping in 541 individuals from eight different human populations allowed the detection of tag SNPs and inversion genotyping in multiple populations worldwide, showing that the inverted allele is mainly found in East Asia with an average frequency of 4.7%. Interestingly, one of the breakpoints disrupts the transcription factor gene ZNF257, causing a significant reduction in the total expression level of this gene in lymphoblastoid cell lines. RNA-Seq analysis of the effects of this expression change in standard homozygotes and inversion heterozygotes revealed distinct expression patterns that were validated by quantitative RT-PCR. Moreover, we have found a new fusion transcript that is generated exclusively from inverted chromosomes around one of the breakpoints. Finally, by the analysis of the associated nucleotide variation, we have estimated that the inversion was generated ~40,000-50,000 years ago and, while a neutral evolution cannot be ruled out, its current frequencies are more consistent with those expected for a deleterious variant, although no significant association with phenotypic traits has been found so far.

Combining MRI with PET for partial volume correction improves image-derived input functions in mice.

Accurate kinetic modelling using dynamic PET requires knowledge of the tracer concentration in plasma, known as the arterial input function (AIF). AIFs are usually determined by invasive blood sampling, but this is prohibitive in murine studies due to low total blood volumes. As a result of the low spatial resolution of PET, image-derived input functions (IDIFs) must be extracted from left ventricular blood pool (LVBP) ROIs of the mouse heart. This is challenging because of partial volume and spillover effects between the LVBP and myocardium, contaminating IDIFs with tissue signal. We have applied the geometric transfer matrix (GTM) method of partial volume correction (PVC) to 12 mice injected with 18F-FDG affected by a Myocardial Infarction (MI), of which 6 were treated with a drug which reduced infarction size [1]. We utilised high resolution MRI to assist in segmenting mouse hearts into 5 classes: LVBP, infarcted myocardium, healthy myocardium, lungs/body and background. The signal contribution from these 5 classes was convolved with the point spread function (PSF) of the Cambridge split magnet PET scanner and a non-linear fit was performed on the 5 measured signal components. The corrected IDIF was taken as the fitted LVBP component. It was found that the GTM PVC method could recover an IDIF with less contamination from spillover than an IDIF extracted from PET data alone. More realistic values of Ki were achieved using GTM IDIFs, which were shown to be significantly different (p<0.05) between the treated and untreated groups.