Juan Carlos Echeverría

Endothelial dysfunction is a hallmark of vascular injury and a central event in cardiovascular and inflammatory diseases. It is characterized by reduced nitric oxide (NO) bioavailability, increased oxidative stress, and disruption of endothelial barrier integrity. Activated neutrophils contribute to this process through the generation of reactive oxygen species and other oxidative mediators. Here, we investigated whether L-arginine, the principal substrate for endothelial NO synthase (eNOS), attenuates neutrophil-induced endothelial injury. Primary human umbilical vein endothelial cells (HUVECs) were exposed to sustained L-arginine supplementation initiated at passage 1 and subsequently challenged with activated neutrophils. Neutrophil exposure reduced stable NO metabolites (NOx), decreased eNOS phosphorylation at Ser1177, increased oxidant-sensitive DCF fluorescence, induced oxidative damage to lipids, proteins, and nucleic acids, disrupted PECAM-1/CD31-associated junctional organization, and increased endothelial permeability. Sustained L-arginine supplementation increased NOx accumulation in neutrophil-exposed cultures, partially preserved eNOS Ser1177 phosphorylation, attenuated oxidative damage, and improved endothelial barrier integrity. Catalase reduced oxidant-sensitive fluorescence and permeability, supporting a ROS-dependent component of the injury model. Targeted PCR array analysis identified neutrophil-associated changes in oxidative stress-related gene-expression patterns; however, direct comparison between L-arginine-supplemented and non-supplemented neutrophil-exposed cultures showed no statistically significant gene-expression changes after Benjamini–Hochberg FDR correction. These findings indicate that L-arginine attenuates neutrophil-induced endothelial injury primarily through biochemical, functional, and structural mechanisms, whereas transcriptional findings should be interpreted as exploratory and hypothesis-generating. Additional studies are required to determine the translational relevance of L-arginine supplementation as a potential approach to preserve endothelial function under oxidative and inflammatory stress.

Cervical dilation during labor is commonly assessed through repeated vaginal examinations, which can be uncomfortable, depend on the observer, and are not suitable for continuous monitoring. This pilot study explored whether machine-learning regression could retrospectively estimate cervical dilation using non-invasive abdominal electrohysterography (EHG) recordings and maternal information. Seventy-two 10-min EHG recordings were collected during labor at two Mexican hospitals. Twenty-one EHG features were calculated from nine overlapping 120-s windows and summarized using eight temporal descriptors, generating 168 temporal EHG features. The recording-level low-contraction (LC) and high-contraction (HC) counts, along with maternal and gestational age, were subsequently appended, yielding a 172-feature vector per recording. After removing five recordings with sparse data outside the 4–8 cm dilation range, 67 records remained—50 for model development and 17 for internal testing. In the development phase, feature ranking, screening of 28 regression models, and genetic-algorithm optimization were performed. The genetic algorithm selected five EHG-derived temporal features for a squared-exponential Gaussian process regression model. During fivefold cross-validation within the development set, the optimized model achieved an RMSE of 0.97 cm, r = 0.67, and R ² = 0.45. On the held-out internal test set, the RMSE was 1.45 cm, with r = 0.23 and R ² = − 0.31. The model showed moderate cross-validated performance during development but limited generalization in the held-out internal test set. These findings are exploratory and do not establish performance for dystocia screening. Larger prospective studies are needed before clinical use can be considered.

The study of inter-beat intervals (IBI) and systolic blood pressure (SBP) fluctuations is of public health importance. Here we obtain insights about their underlying dynamics by means of an innovative study of the distribution of their rank-ordered registers, provided by fits to the Discrete Generalized Beta Distribution (DGBD), for healthy subjects and patients with end-stage renal disease (ESRD), under an active standing maneuver. SBP and IBI non-invasive time series were recorded during supine position followed by active standing for nine ESRD patients and eighteen age-matched healthy subjects. Once the data were rank ordered, the three parameter DGBD function was fitted through the Levenberg–Marquardt non-linear algorithm. Taking into consideration the statistical interpretations of the parameters, the quantitative exploration of their dependence with regard to the cases examined and changes in body position provided new insights: (i) Evidence for the presence of regulatory mechanisms that preserve the tail symmetry of the IBI distributions in healthy subjects, which are not evident in ESRD patients; (ii) The identification of a more pronounced weight of low-magnitude fluctuations at active standing in the SBP time series, manifested as a broader statistical dispersion of blood pressure values; (iii) A quantitative determination of a more undermined SBP regulation in ESRD. Overall, a better understanding of the statistical behavior of IBI and SBP time series is achieved by means of the DGBD function. Through the variation of its parameters, the DGBD approach has the potential to become a marker for assessing or even predicting the impairment of cardiovascular control mechanisms.

Purpose: This study evaluates whether indices extracted from different frequency bands of electrohysterography (EHG) can distinguish among cervical dilation levels during the first stage of labor. EHG, a non-invasive method for recording uterine electrical activity, can be analyzed in three bands: Band 1 (0.2–1 Hz), Band 2 (0.34–1 Hz, FWH), and Band 3 (0.2–0.34 Hz, FWL). The Fast Wave High (FWH) band reflects uterine excitability, while the Fast Wave Low (FWL) band is linked to electrical activity propagation. Methods: Seventy-three transabdominal EHG recordings (10 min each) were analyzed from women in labor, categorized by cervical dilation: low (1–4 cm), moderate (5–6 cm), and advanced (7–10 cm). Linear indices (Root Mean Square [RMS], Area Under the Curve [AUC], Zero Crossing Rate [ZCR], Median Frequency [MDF]) and a nonlinear index (Sample Entropy [SampEn]) were calculated for Bands 1, 2, and 3. Results: In Band 2, ZCR and MDF increased significantly with advanced dilation, suggesting increasing uterine excitability accompanied by more frequent contractions. Correlation analysis revealed a positive relationship between these indices and cervical dilation. By contrast, in Band 3, SampEn decreased with advanced dilation, suggesting more synchronized and regular contractions. Conclusion: EHG indices in Bands 2 and 3 may serve as complementary, noninvasive, and innocuous biomarkers of labor progression. In Band 2, increases in ZCR and MDF reflect heightened uterine excitability, while in Band 3, decreased SampEn suggests more synchronized contractions. These findings may improve labor monitoring by providing real-time insights to support clinical decisions, and potentially enhance maternal and neonatal outcomes.

Introduction: Aortic valve disease (AVD) is an inflammatory, lipid infiltration and calcification disease that has been associated with changes in the conventional linear heart rate variability (HRV) indices showing a marked shift towards sympathetic predominance and a deterioration of the autonomic control. Objective: To explore the HRV dynamics in AVD patients through nonlinear methods by recurrence quantification analysis (RQA). Methods: In total, 127 subjects participated in a cross-sectional study categorized into three groups: healthy valve (HV), aortic valve sclerosis (AVSc), and aortic valve stenosis (AVS), as determined by echocardiographic assessment. HRV data were collected from five-minute ECG recordings at both a supine position and active standing. RQA indices were calculated using the Cross Recurrence Plot Toolbox. Results: In the supine position, patients with AVS exhibited larger determinism and trapping time than those with AVSc and HV. The analysis of these differences revealed that determinism and laminarity increased progressively from HV to AVS. In the same way, the magnitude of change (Δ) between positions decreased and presented the lowest values in AVS in most of the nonlinear indices. Conclusion: RQA indices of HRV in AVD patients indicate a rigidizing dynamic characterized by larger determinism and extended trapping times in fewer system states in relation to the severity of AVD. These findings establish a precedent for future perspective assessments for the implementation of these methods in medical software or devices.

Music has been shown to influence physiological functions in humans, but its effects on fetal heart rate variability (fHRV) are not well understood. This study aimed to assess the response of classical music exposure on the nonlinear behavior of fetal heart rate fluctuations in fetuses between 32 and 40 weeks of gestation using recurrence quantification analysis (RQA). We collected R–R time series from 37 fetuses in the third trimester following a study into four stages: PRE (baseline), STIM1 (first musical piece), STIM2 (second musical piece), and POST (post-exposure). The fetal R–R time series from each stage were evaluated using RQA indices such as determinism (DET), average diagonal line length (L), maximum line length (LMAX), entropy (ENTR), and trapping time (TT), as well as conventional linear indices like SDRR (standard deviation of R–R intervals). Results revealed three main points. First, there was an increase in DET, L, LMAX, and TT, with a decrease in ENTR in the POST stage compared to PRE, indicating more regular and predictable patterns. Second, the STIM2 stage enhanced the predictability and stability of cardiac dynamics compared to PRE, as indicated by L, LMAX, and TT. Third, no significant changes were observed in conventional indices, except for an increase in SDRR in the POST stage compared to STIM1. These findings suggest a reduction in complexity and nonlinear behavior of fHRV patterns after musical stimulus. The increase in SDRR during the POST stage appears to coincide with fetal movements, as indicated by the number of fetal accelerations found.

This research explores maternal–fetal heart rhythm coupling (MFHRC) in full-term and moderate preterm labor using high-resolution joint symbolic dynamics (HRJSD) to identify distinct heart rate patterns indicative of physiological system couplings during active labor stages. This study evidences that preterm labor exhibits unique MFHRC patterns compared to full-term labor, potentially reflecting physiological responses and system complexities differences. The analysis involved 25 maternal–fetal RR time series from women in active full-term labor and 18 from those in moderate preterm labor. HRJSD was utilized to dissect the degree of coupling by examining specific maternal–fetal heart rhythm patterns and calculating global Shannon entropy for both groups. We observed that specific dominant heart rate patterns are preserved in both term and moderate preterm labor, suggesting an intrinsic aspect of cardiovascular coupling irrespective of the labor's condition. Additionally, we found variations in non-dominant patterns between term and preterm labor, which may reflect subtle differences in cardiac responses, hinting at possible adaptive fetal strategies in response to preterm labor conditions. An important finding of our research is the overall decrease in MFHRC in preterm labor, as indicated by higher Shannon entropy values. This decrease suggests a reduced synchronization of maternal–fetal heart rate rhythm during labor in preterm conditions. These insights highlight the importance of MFHRC analysis in understanding the distinct physiological interactions between mother and fetus during labor. The study's findings may pave the way for further research on prenatal health and developing interventions that may guide outcomes in preterm labor.