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.

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.

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.

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.

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.

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.

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.

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.

Validation and genotyping of multiple human polymorphic inversions mediated by inverted repeats reveals a high degree of recurrence.

In recent years different types of structural variants (SVs) have been discovered in the human genome and their functional impact has become increasingly clear. Inversions, however, are poorly characterized and more difficult to study, especially those mediated by inverted repeats or segmental duplications. Here, we describe the results of a simple and fast inverse PCR (iPCR) protocol for high-throughput genotyping of a wide variety of inversions using a small amount of DNA. In particular, we analyzed 22 inversions predicted in humans ranging from 5.1 kb to 226 kb and mediated by inverted repeat sequences of 1.6-24 kb. First, we validated 17 of the 22 inversions in a panel of nine HapMap individuals from different populations, and we genotyped them in 68 additional individuals of European origin, with correct genetic transmission in ∼ 12 mother-father-child trios. Global inversion minor allele frequency varied between 1% and 49% and inversion genotypes were consistent with Hardy-Weinberg equilibrium. By analyzing the nucleotide variation and the haplotypes in these regions, we found that only four inversions have linked tag-SNPs and that in many cases there are multiple shared SNPs between standard and inverted chromosomes, suggesting an unexpected high degree of inversion recurrence during human evolution. iPCR was also used to check 16 of these inversions in four chimpanzees and two gorillas, and 10 showed both orientations either within or between species, providing additional support for their multiple origin. Finally, we have identified several inversions that include genes in the inverted or breakpoint regions, and at least one disrupts a potential coding gene. Thus, these results represent a significant advance in our understanding of inversion polymorphism in human populations and challenge the common view of a single origin of inversions, with important implications for inversion analysis in SNP-based studies.

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.

Versatile lock and key assembly for optical measurements with microfluidic platforms and cartridges.

A novel and versatile optical reader for microfluidic platforms is presented. The reader includes a modular insertion port based on the lock and key concept for reproducible alignment with a miniaturized optical detection system comprising an interchangeable light emitting diode (LED) and a photodiode. The modular nature of the insertion port allows the use of microfluidic platforms in variable shapes and fluidic configurations. Three different analytical methodologies based on absorbance or fluorescence measurements were used to demonstrate the flexibility and reproducibility of the proposed experimental setup.

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.

A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment.

Through the combined use of (18)F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design. Although patients with attention deficit/hyperactivity disorder as a group showed significant attentional deficits and reduced grey matter volume in fronto-striato-cerebellar and limbic networks, they had equivalent D2/D3 receptor availability and equivalent increases in endogenous dopamine after methylphenidate treatment to that observed in healthy control subjects. However, poor attentional performers drawn from both the attention deficit/hyperactivity disorder and the control groups had significantly reduced left caudate dopamine activity. Methylphenidate significantly increased dopamine levels in all nigro-striatal regions, thereby normalizing dopamine levels in the left caudate in low performers. Behaviourally, methylphenidate improved sustained attention in a baseline performance-dependent manner, irrespective of diagnosis. This finding was accompanied by an equally performance-dependent effect of the drug on dopamine release in the midbrain, whereby low performers showed reduced dopamine release in this region. Collectively, these findings support a dimensional model of attentional deficits and underlying nigro-striatal dopaminergic mechanisms of attention deficit/hyperactivity disorder that extends into the healthy population. Moreover, they confer midbrain dopamine autoreceptors a hitherto neglected role in the therapeutic effects of oral methylphenidate in attention deficit/hyperactivity disorder. The absence of significant case-control differences in D2/D3 receptor availability (despite the observed relationships between dopamine activity and attention) suggests that dopamine dysregulation per se is unlikely to be the primary cause underlying attention deficit/hyperactivity disorder pathology in adults. This conclusion is reinforced by evidence of neuroanatomical changes in the same set of patients with attention deficit/hyperactivity disorder.

Atrial lead placement at the lower atrial septum: a potential strategy to reduce unnecessary right ventricular pacing.

AIMS: Right ventricular (RV) pacing has been shown to be potentially detrimental to left ventricular function. In conventional dual-chamber pacing the position of the atrial lead could influence duration of the atrio-ventricular (AV) intervals, which is one of the variables that could be associated with an increased percentage of RV pacing. We wanted to see if lead placement at selected atrial septal sites could reduce AV intervals in patients receiving a dual-chamber pacemaker or implantable cardioverter defibrillator. METHODS AND RESULTS: This was a prospective, acute, randomized single centre study that enrolled 57 patients. The atrial lead was placed in both the right atrial appendage (RAA) and the lower atrial septum (LAS) in each patient in random order. The P-wave durations, PR intervals, A sense-V sense (As-Vs), and A pace-V sense (Ap-Vs) intervals were measured at both atrial lead locations in each patient during device implant. The P-wave durations during sinus rhythm (SR), RAA pacing, and LAS pacing were 113 ± 19, 144 ± 27, and 84 ± 12 ms (RAA vs. LAS, P < 0.001), respectively. The PR intervals during SR, RAA pacing, and LAS pacing were 195 ± 47, 230 ± 61, and 167 ± 44 ms (RAA vs. LAS, P < 0.001), respectively. The As-Vs interval was 31% shorter in LAS pacing than in RAA pacing (134 ± 44 ms vs. 194 ± 52 ms, P < 0.001). The Ap-Vs interval was 24% shorter during LAS pacing than during RAA pacing (195 ± 45 ms vs. 257 ± 63 ms, P < 0.001). CONCLUSION: When compared with RAA pacing, LAS pacing was associated with a shorter P wave duration, PR interval, As-Vs, and Ap-Vs intervals. The potential long-term impact of the strategy of pacing from LAS in reducing unnecessary RV pacing needs to be explored in future studies.

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.

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.

Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory.

Previous data suggest that methylphenidate can have variable effects on different cognitive tasks both within and between individuals. This is thought to be underpinned by inverted U-shaped relationships between cognitive performance and dopaminergic activity in relatively separate fronto-striatal circuits and reflected by individual differences in trait impulsivity. Direct evidence for this is currently lacking. In this study, we demonstrate for the first time that therapeutic doses of oral methylphenidate administered to young healthy subjects result in different sized changes in D(2)/D(3) receptor availability in different regions of the human striatum and that the change in receptor availability within an individual subregion predicts cognitive performance on a particular task. Methylphenidate produced significantly different effects on reversal learning and spatial working memory tasks within individuals. Performance on the reversal learning task was predicted by the drug-induced change in D(2)/D(3) receptor availability in postcommissural caudate, measured using [(11)C]-raclopride radioligand PET imaging, whereas performance on the spatial working memory task was predicted by changes in receptor availability in the ventral striatum. Reversal learning performance was also predicted by subjects' trait impulsivity, such that the most impulsive individuals benefited more from methylphenidate, consistent with this drug's beneficial effects on cognition in attention deficit hyperactivity disorder.

[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)..