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Complexity analysis of short-term cardiovascular control is traditionally performed using entropy-based approaches including corrective terms or strategies to cope with the loss of reliability of conditional distributions with pattern length. This study proposes a new approach aiming at the estimation of conditional entropy (CE) from short data segments (about 250 samples) based on the k-nearest-neighbor technique. The main advantages are: (i) the control of the loss of reliability of the conditional distributions with the pattern length without introducing a priori information; (ii) the assessment of complexity indexes without fixing the pattern length to an arbitrary low value. The approach, referred to as k-nearest-neighbor conditional entropy (KNNCE), was contrasted with corrected approximate entropy (CApEn), sample entropy (SampEn) and corrected CE (CCE), being the most frequently exploited approaches for entropy-based complexity analysis of short cardiovascular series. Complexity indexes were evaluated during the selective pharmacological blockade of the vagal and/or sympathetic branches of the autonomic nervous system. We found that KNNCE was more powerful than CCE in detecting the decrease of complexity of heart period variability imposed by double autonomic blockade. In addition, KNNCE provides indexes indistinguishable from those derived from CApEn and SampEn. Since this result was obtained without using strategies to correct the CE estimate and without fixing the embedding dimension to an arbitrary low value, KNNCE is potentially more valuable than CCE, CApEn and SampEn when the number of past samples most useful to reduce the uncertainty of future behaviors is high and/or variable among conditions and/or groups. [ABSTRACT FROM AUTHOR]

Mental processes bring about neural, vascular and autonomic changes in the brain cortex. Due to the different nature of these modifications, their onsets show no synchrony and time dynamics is often strongly dissimilar. After acquiring data from a group of 16 subjects, we estimated temporal correlation between task and signals in order to assess possible influences induced by an attentive task on electroencephalographic (EEG), heart rate variability (HRV), oxy- and deoxy-haemoglobin concentration signals. We also investigated correlations and time delays between couples of different biological signals. This allowed for the isolation of a subgroup of subjects showing similar tracks. Cardiac frequency and deoxy-haemoglobin signals displayed a strong positive correlation with the task design, while EEG alpha rhythm and oxygenation showed a negative correlation. Neural electrical response was nearly instantaneous with respect to the task progression, and autonomic response showed a mean delay of about 15 s and a slower hemodynamic response (mean delay above 20 s) was finally induced. Globally, the task elicited a cascade of responses, in which delays can be quantified. [ABSTRACT FROM AUTHOR]

Background/Objectives : Carotid artery stenosis (CAS) is one of the main causes of stroke, and the vulnerability of plaque has been proved to be a determinant. A joint analysis of shear wave elastography, a radiofrequency echo-based wall tracking technique for arterial stiffness evaluation, and of autonomic and baroreflex function is proposed to noninvasively, preoperatively assess plaque vulnerability in asymptomatic CAS patients scheduled for carotid endarterectomy. Methods : Elastographic markers of arterial stiffness were derived preoperatively in 78 CAS patients (age: 74.2 + 7.7 years, 27 females). Autonomic and baroreflex markers were also assessed by means of an analysis of the beat-to-beat fluctuations in heart period and systolic arterial pressure, derived at rest in supine position (REST) and during active standing. Postoperative analysis identified 36 patients with vulnerable plaque (VULN) and 42 with stable plaque (STABLE). Results : Baroreflex sensitivity (BRS) at a respiratory rate decreased during STAND only in VULN patients, being much higher at REST compared to STABLE levels. Autonomic indexes were not helpful in separating experimental conditions and/or populations. The Young's modulus (YM) of the plaque was lower in the VULN group than in the STABLE one. Cardiovascular control and elastographic markers were significantly correlated only in VULN patients. A multivariate logistic regression model built combining YM and BRS at the respiratory rate improved the prediction of plaque vulnerability, reporting an area under the ROC curve of 0.694. Conclusions : Noninvasive techniques assessing shear wave elastography and baroreflex control could contribute to the early detection of plaque vulnerability in patients with asymptomatic CAS.

Due to high lipophilicity and extensive first-pass metabolic loss, cannabidiol (CBD) has low oral bioavailability. Co-administration of CBD and long-chain lipids facilitates the intestinal lymphatic delivery, resulting in higher systemic bioavailability, as well as high levels of the drug within the intestinal lymphatic system. However, despite previous attempts with various lipid-based formulations, the oral bioavailability of CBD is still limited. In this work, we have developed a novel formulation of CBD based on natural rapeseed oleosomes. In vivo studies in rats demonstrated that oral administration of CBD-loaded rapeseed oleosomes leads to substantially higher oral bioavailability and intestinal lymphatic targeting of CBD in comparison with rapeseed oil or artificial emulsion made of rapeseed oil and lecithin. In vitro mechanistic assessments, including in vitro lipolysis and peroxide value determination suggest that the lower oxidative state of the oil in oleosomes in comparison to crude oil or artificial emulsion is likely to be the main factor responsible for the superior performance of the CBD-loaded rapeseed oleosomes in vivo. Although further investigation will be needed, the data suggest that natural seeds-derived oleosomes can be used as a promising lipid-based drug delivery platform promoting the bioavailability and lymphatic delivery of lipophilic drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Tuberculosis (TB) remains a Global Health challenge, with diagnostic delays contributing significantly to its spread. This study investigates the differences in diagnostic delays between native and migrant TB patients in Italy, examining patient-related diagnostic delay (PDD), health system-related diagnostic delay (HDD), and total diagnostic delay (TDD)., Methods: We conducted a retrospective, multicenter, cross-sectional study of TB cases in 10 Italian hospitals from 2018 to 2023. We compared PDD, HDD, and TDD between native and migrant populations. Socio-demographic data and clinical histories were analyzed to identify factors contributing to diagnostic delays., Results: We included 669 TB patients (390 migrants and 279 natives). Migrants experienced significantly longer PDD (median 90 vs 10 days, P < 0.0001) but shorter HDD (median 5 vs 40 days, P < 0.0001) compared to natives, resulting in a longer TDD (median 96 vs 65 days, P < 0.0001). Furthermore, migrants had higher Timika scores, longer sputum conversion times, and were more frequently lost to follow-up., Conclusion: Migrants face longer PDD, emphasizing substantial barriers to healthcare access. Natives experience longer HDD, reflecting neglect of TB in low-endemic regions. Future research should focus on the impact of social determinants and training for healthcare providers on TB diagnosis and develop strategies to reduce diagnostic delays., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with carotid stenosis can receive indication for either carotid endarterectomy (CEA) or carotid artery stenting (CAS), with both techniques having an impact on the autonomic function and baroreflex control.Seventy carotid stenosis patients randomly assigned to CEA or CAS were enrolled. After exclusion of some recordings, 33 CEA (age 67.79 ± 5.32 yrs, 26 males) and 25 CAS (age 70.32 ± 3.63 yrs, 14 males) were admitted to analysis. Autonomic and baroreflex sensitivity markers were derived from the analysis of heart period and systolic arterial pressure spontaneous variability derived in supine position and during active standing (STAND), before (PRE) the intervention and after a 6 and 12-month follow-up (FU6, FU12).CEA had a preserved response of autonomic and baroreflex control to STAND in PRE and FU6, suggesting an early improvement. CAS had a similar response at PRE but a blunted one at the follow-ups. When directly compared, the two groups had a similar autonomic function, with CAS having a reduced baroreflex control in PRE and lower autonomic function at FU6. All the differences disappeared at the long-term follow-up, showing a similar long term effect of the surgical procedures, suggesting that CEA and CAS induced a similar long-term impairment of autonomic and baroreflex controls., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

There are several mechanisms responsible for the dynamical link between heart period (HP) and respiration (R), usually referred to as cardiorespiratory coupling (CRC). Historically, diverse signal processing techniques have been employed to study CRC from the spontaneous fluctuations of HP and respiration (R). The proposed tools differ in terms of rationale and implementation, capturing diverse aspects of CRC. In this review, we classify the existing methods and stress differences with the aim of proposing a variability-based multi-method approach to CRC evaluation. Ten methodologies for CRC estimation, namely, power spectral decomposition, traditional and causal squared coherence,\;information transfer, cross-conditional entropy, mixed prediction, Shannon entropy of the latency between heartbeat and inspiratory/expiratory onset, conditional entropy of the phase dynamics, synchrogram-based analysis, pulse-respiration quotient, and joint symbolic dynamics, are considered. The ability of these techniques was exemplified over recordings acquired from patients suffering from postural orthostatic tachycardia syndrome (POTS) and healthy controls. Analyses were performed at rest in the supine position (REST) and during head-up tilt (HUT). Although most of the methods indicated that at REST, the CRC was lower in POTS patients and decreased more evidently during HUT in POTS, peculiar differences stressed the complementary value of the approaches. The multiple perspectives provided by the variability-based multi-method approach to CRC evaluation help the characterization of a pathological state and/or the quantification of the effect of a postural challenge. The present work stresses the need for the application of multiple methods to derive a more complete evaluation of the CRC in humans., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Aortic valve stenosis (AVS) is a common valvular heart disease affecting millions of people worldwide. It leads to significant neurocognitive and neuropsychological impairments, impacting patients' quality of life., Objective: The objective of this article is to identify and discuss the potential neurocognitive effects on patients with aortic stenosis before and after undergoing surgical aortic valve replacement (SAVR)., Method: Our study involved the assessment of 64 patients undergoing aortic valve replacement (SAVR) using a neurocognitive evaluation comprising a battery of 11 different cognitive tests. These tests were designed to analyze the patients' overall cognitive functioning, executive abilities, short- and long-term memory, and attentional performance. The tests were administered to patients before the aortic valve surgery (T0) and after the surgery (T1). From a statistical perspective, numerical variables are presented as means (±standard deviation) and medians (IQR), while categorical variables are presented as counts and percentages. Normality was assessed using the Shapiro-Wilk test. T0 and T1 scores were compared with the Wilcoxon signed rank test, with p < 0.05 considered significant. Analyses were performed using SAS version 9.4., Results: Conducted as part of a fully financed Italian Ministry of Health project (RF-2016-02361069), the study found that most patients showed normal cognitive functioning at baseline. Cognitive assessments showed that executive functions, attention, language, and semantic knowledge were within the normal range for the majority of participants. After SAVR, cognitive outcomes remained stable or improved, particularly in executive functions and language. Notably, verbal episodic memory demonstrated significant improvement, with the percentage of patients scoring within the normal range on the BSRT increasing from 73.4% at T0 to 92.2% at T1 ( p < 0.0001). However, visuospatial and visuoconstructive abilities showed stability or slight decline, while attentional skills remained relatively stable. The Clock Drawing Test indicated the maintenance of cognitive functions., Conclusions: The findings of our study indicate a global stability in cognitive status among patients after undergoing SAVR, with significant improvement noted in verbal episodic memory. While other cognitive domains did not demonstrate statistically significant changes, these insights are valuable for understanding the cognitive effects of SAVR and can guide future research and clinical practice in selecting the most effective surgical and rehabilitative options for patients. Monitoring cognitive outcomes in patients undergoing aortic valve replacement surgery remains crucial.

Surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are options in severe aortic valve stenosis (AVS). Cardiovascular (CV) and cerebrovascular (CBV) control markers, derived from variability of heart period, systolic arterial pressure, mean cerebral blood velocity and mean arterial pressure, were acquired in 19 AVS patients (age: 76.8 ± 3.1 yrs, eight males) scheduled for SAVR and in 19 AVS patients (age: 79.9 + 6.5 yrs, 11 males) scheduled for TAVI before (PRE) and after intervention (POST, <7 days). Left ventricular function was preserved in both groups. Patients were studied at supine resting (REST) and during active standing (STAND). We found that: (i) both SAVR and TAVI groups featured a weak pre-procedure CV control; (ii) TAVI ensured better CV control; (iii) cerebral autoregulation was working in PRE in both SAVR and TAVI groups; (iv) SAVR and TAVI had no impact on the CBV control; (v) regardless of group, CV and CBV control markers were not influenced by STAND in POST. Even though the post-procedure preservation of both CV and CBV controls in TAVI group might lead to privilege this procedure in patients at higher risk, the missing response to STAND suggests that this advantage could be insignificant., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

We tested the validity of the state space correspondence (SSC) strategy based on k-nearest neighbor cross-predictability (KNNCP) to assess the directionality of coupling in stochastic nonlinear bivariate autoregressive (NBAR) processes. The approach was applied to assess closed-loop cardiorespiratory interactions between heart period (HP) variability and respiration (R) during a controlled respiration (CR) protocol in 19 healthy humans (aged from 27 to 35 yrs, 11 females) and during active standing (STAND) in 25 athletes (aged from 20 to 40 yrs, all men) and 25 non-athletes (aged from 20 to 40 yrs, all men). Over simulated NBAR processes, we found that (i) the SSC approach can detect the correct causal relationship as the direction leads to better KNNCP from the past of the driver to the future state of the target and (ii) simulations suggest that the ability of the method is preserved in any condition of complexity of the interacting series. Over CR and STAND protocols, we found that (a) slowing the breathing rate increases the strength of the causal relationship in both temporal directions in a balanced modality; (b) STAND is more powerful in modulating the coupling strength on the pathway from HP to R; (c) regardless of protocol and experimental condition, the strength of the link from HP to R is stronger than that from R to HP; (d) significant causal relationships in both temporal directions are found regardless of the level of complexity of HP variability and R. The SSC strategy is useful to disentangle closed-loop cardiorespiratory interactions., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Background : Autonomic function and baroreflex control might influence the survival rate of coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to respiratory failure patients without COVID-19 (non-COVID-19). This study describes physiological control mechanisms in critically ill COVID-19 patients admitted to the ICU in comparison to non-COVID-19 individuals with the aim of improving stratification of mortality risk. Methods : We evaluated autonomic and baroreflex control markers extracted from heart period (HP) and systolic arterial pressure (SAP) variability acquired at rest in the supine position (REST) and during a modified head-up tilt (MHUT) in 17 COVID-19 patients (age: 63 ± 10 years, 14 men) and 33 non-COVID-19 patients (age: 60 ± 12 years, 23 men) during their ICU stays. Patients were categorized as survivors (SURVs) or non-survivors (non-SURVs). Results : We found that COVID-19 and non-COVID-19 populations exhibited similar vagal and sympathetic control markers; however, non-COVID-19 individuals featured a smaller baroreflex sensitivity and an unexpected reduction in the HP-SAP association during the MHUT compared to the COVID-19 group. Nevertheless, none of the markers of the autonomic and baroreflex functions could distinguish SURVs from non-SURVs in either population. Conclusions : We concluded that COVID-19 patients exhibited a more preserved baroreflex control compared to non-COVID-19 individuals, even though this information is ineffective in stratifying mortality risk.

This study investigates the potential use of peanut oil bodies as a fat replacer in ice cream. We explored the effects of different treatments, fresh (FOB), heated (HOB), and roasted (ROB) peanut oil bodies on ice cream preparation. Heat treatment altered the intrinsic protein profile on the oil bodies' surface, subsequently influencing the ice cream's properties. Notably, heat treatment increases the oil bodies' size and the absolute value of ζ-potential. The rheological analysis provided information about void volumes, indicating easier air incorporation during whipping for ROB (72 to 300 nm) than FOB (107 to 55 nm). ROB ice cream displays a high overrun and a lower melting rate compared to FOB ice cream. Moreover, thermal treatment reduces the beany flavors, n-hexanal, and 2-pentenylfuran. Overall, this study reveals peanut oil bodies as a promising platform for rational design of fat-substituted plant-based ice creams., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Remote work (REMOTE) causes an overlap between working and domestic demands. The study of the cardiac autonomic profile (CAP) by means of heart rate variability (HRV) provides information about the impact of REMOTE on workers' health. The primary aim was to determine whether CAP, self-perceived stress, environmental and workstation comfort are modified during REMOTE. The secondary aim was to explore how these indices are influenced by individual and environmental work-related factors. Fifty healthy office employees alternating REMOTE and in-office (OFFICE) working were enrolled, rated self-perceived stress, environmental and workstation comfort using a visual analogue scale and performed a 24-h electrocardiogram during REMOTE and OFFICE. Stress was lower (5.6 ± 2.2 vs. 6.4 ± 1.8), environmental comfort higher (7.7 ± 1.9 vs. 7.0 ± 1.5), and the workstation comfort poorer (6.2 ± 1.8 vs. 7.5 ± 1.2) during REMOTE. CAP was similar during REMOTE and OFFICE. CAP was influenced by some work-related factors, including the presence of offspring, absence of a dedicated workspace during REMOTE and number of working hours. All these variables determined a decreased vagal modulation. The working setting seems to impact the levels of perceived stress and comfort, but not the CAP. However, individual and environmental work-related factors reduce cardiac vagal modulation during REMOTE, potentially increasing the risk of developing cardiovascular diseases., (© 2024. The Author(s).)

The evaluation of propensity to postural syncope necessitates the concomitant characterization of the cardiovascular and cerebrovascular controls and a method capable of disentangling closed loop relationships and decomposing causal links in the frequency domain. We applied Geweke spectral causality (GSC) to assess cardiovascular control from heart period and systolic arterial pressure variability and cerebrovascular regulation from mean arterial pressure and mean cerebral blood velocity variability in 13 control subjects and 13 individuals prone to develop orthostatic syncope. Analysis was made at rest in supine position and during head-up tilt at 60°, well before observing presyncope signs. Two different linear model structures were compared, namely bivariate autoregressive and bivariate dynamic adjustment classes. We found that (i) GSC markers did not depend on the model structure; (ii) the concomitant assessment of cardiovascular and cerebrovascular controls was useful for a deeper comprehension of postural disturbances; (iii) orthostatic syncope appeared to be favored by the loss of a coordinated behavior between the baroreflex feedback and mechanical feedforward pathway in the frequency band typical of the baroreflex functioning during the postural challenge, and by a weak cerebral autoregulation as revealed by the increased strength of the pressure-to-flow link in the respiratory band. GSC applied to spontaneous cardiovascular and cerebrovascular oscillations is a promising tool for describing and monitoring disturbances associated with posture modification., (© 2023. The Author(s).)

Objective. The percentages of cardiac and sympathetic baroreflex patterns detected via baroreflex sequence (SEQ) technique from spontaneous variability of heart period (HP) and systolic arterial pressure (SAP) and of muscle nerve sympathetic activity (MSNA) burst rate and diastolic arterial pressure (DAP) are utilized to assess the level of the baroreflex engagement. The cardiac baroreflex patterns can be distinguished in those featuring both HP and SAP increases (cSEQ++) and decreases (cSEQ--), while the sympathetic baroreflex patterns in those featuring a MSNA burst rate decrease and a DAP increase (sSEQ+-) and vice versa (sSEQ-+). The present study aims to assess the modifications of the involvement of the cardiac and sympathetic arms of the baroreflex with age and postural stimulus intensity. Approach. We monitored the percentages of cSEQ++ (%cSEQ++) and cSEQ-- (%cSEQ--) in 100 healthy subjects (age: 21-70 years, 54 males, 46 females), divided into five sex-balanced groups consisting of 20 subjects in each decade at rest in supine position and during active standing (STAND). We evaluated %cSEQ++, %cSEQ--, and the percentages of sSEQ+- (%sSEQ+-) and sSEQ-+ (%sSEQ-+) in 12 young healthy subjects (age 23 ± 2 years, 3 females, 9 males) undergoing incremental head-up tilt. Main results. We found that: (i) %cSEQ++ and %cSEQ-- decreased with age and increased with STAND and postural stimulus intensity; (ii) %sSEQ+- and %sSEQ-+ augmented with postural challenge magnitude; (iii) the level of cardiac and sympathetic baroreflex engagement did not depend on either the absolute value of arterial pressure or the direction of its changes. Significance. This study stresses the limited ability of the cardiac and sympathetic arms of the baroreflex in controlling absolute arterial pressure values and the equivalent ability of both positive and negative arterial pressure changes in soliciting them., (Creative Commons Attribution license.)

Objective. Aortic valve stenosis (AVS) induces left ventricular function adaptations and surgical aortic valve replacement (SAVR) restores blood flow profile across aortic valve. Modifications of cardiac hemodynamics induced by AVS and SAVR might alter cardiovascular (CV) and cerebrovascular (CBV) controls. The study aims at characterizing CV and CBV regulations one day before SAVR (PRE), within one week after SAVR (POST), and after a three-month follow-up (POST3) in 73 AVS patients (age: 63.9 ± 12.9 yrs; 48 males, 25 females) from spontaneous fluctuations of heart period (HP), systolic arterial pressure, mean arterial pressure and mean cerebral blood velocity. Approach. CV and CBV regulations were typified via a bivariate autoregressive approach computing traditional frequency domain markers and causal squared coherence ( CK 2 We found that: (i) CV regulation is impaired in AVS patients; (ii) CV regulation worsens in POST; (iii) CV regulation recovers in POST3 and CV response to active standing is even better than in PRE; (iv) CBV regulation is preserved in AVS patients; (v) SAVR does not affect CBV control; (vi) parameters of the CBV control in POST3 and PRE are similar. Main results. We found that: (i) CV regulation is impaired in AVS patients; (ii) CV regulation worsens in POST; (iii) CV regulation recovers in POST3 and CV response to active standing is even better than in PRE; (iv) CBV regulation is preserved in AVS patients; (v) SAVR does not affect CBV control; (vi) parameters of the CBV control in POST3 and PRE are similar. Significance. CK 2 is particularly useful to characterize CV and CBV controls in AVS patients and to monitor of patient's evolution after SAVR., (Creative Commons Attribution license.)

Introduction: Joint symbolic analysis (JSA) can be utilized to describe interactions between time series while accounting for time scales and nonlinear features. JSA is based on the computation of the rate of occurrence of joint patterns built after symbolization. Lagged JSA (LJSA) is obtained from the more classical JSA by introducing a delay/lead between patterns built over the two series and combined to form the joint scheme, thus monitoring coordinated patterns at different lags. Methods: In the present study, we applied LJSA for the assessment of cardiorespiratory coupling (CRC) from heart period (HP) variability and respiratory activity (R) in 19 healthy subjects (age: 27-35 years; 8 males, 11 females) during spontaneous breathing (SB) and controlled breathing (CB). The R rate of CB was selected to be indistinguishable from that of SB, namely, 15 breaths·minute -1 (CB15), or slower than SB, namely, 10 breaths·minute -1 (CB10), but in both cases, very rapid interactions between heart rate and R were known to be present. The ability of the LJSA approach to follow variations of the coupling strength was tested over a unidirectionally or bidirectionally coupled stochastic process and using surrogate data to test the null hypothesis of uncoupling. Results: We found that: i) the analysis of surrogate data proved that HP and R were significantly coupled in any experimental condition, and coupling was not more likely to occur at a specific time lag; ii) CB10 reduced CRC strength at the fastest time scales while increasing that at intermediate time scales, thus leaving the overall CRC strength unvaried; iii) despite exhibiting similar R rates and respiratory sinus arrhythmia, SB and CB15 induced different cardiorespiratory interactions; iv) no dominant temporal scheme was observed with relevant contributions of HP patterns either leading or lagging R. Discussion: LJSA is a useful methodology to explore HP-R dynamic interactions while accounting for time shifts and scales., Competing Interests: The author(s) AP, BDM, FG, VB, BC declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Cairo, Bari, Gelpi, De Maria and Porta.)

Granger causality (GC) analysis is based on the comparison between prediction error variances computed over the full and restricted models after identifying the coefficients of appropriate vector regressions. GC markers can be computed via a double regression (DR) approach identifying two separate, independent models and a single regression (SR) strategy optimizing the description of the dynamics of the target over the full model and, then, reusing some parts of it in the restricted model. The present study compares the SR and DR strategies over heart period (HP), systolic arterial pressure (SAP) and respiration (R) beat-to-beat series collected during a graded orthostatic challenge induced by head-up tilt in 17 healthy individuals (age: 21-36 yrs; median: 29 yrs; 9 females and 8 males). We found that the DR approach was more powerful than the SR one in detecting the expected stronger involvement of the baroreflex during the challenge, while the expected weaker cardiorespiratory coupling was identified by both SR and DR strategies. The less powerful ability of the SR approach was the result of the greater variance of GC markers compared to the DR strategy. We conclude that, contrary to the suggestions present in literature, the SR approach is not necessarily associated with a smaller dispersion of GC markers. Moreover, we suggest that additional factors, such as the strategy utilized to build embedding spaces and metric utilized to compare prediction error variances, might play an important role in differentiating SR and DR approaches.

Although the autonomic influence on cardiovascular (CV) and cerebrovascular (CBV) regulations has been widely recognized, their relationship is poorly explored especially in pathological situations. This study investigates the correlation between CV and CBV markers in 73 patients (48 males, age 63.6±13.1 yrs) undergoing surgical aortic valve replacement (SAVR) evaluated before the intervention (PRE), within 1-week post-surgery (POST) and after a 3-month follow-up (POST3). Patients were acquired before and after an orthostatic challenge. Frequency domain analysis assessing transfer function gain (TFG), phase (Ph), and squared coherence (K 2 ) between heart period and systolic arterial pressure was exploited to evaluate CV control. The same frequency domain functions were derived to assess CBV regulation from mean cerebral blood velocity and mean arterial pressure. A correlation analysis between indexes of CV and CBV controls was carried out. Results showed that CV control was impaired in PRE, worsened in POST, and recovered in POST3, while CBV markers were almost unchanged. A significant positive relationship between CV and CBV markers was observed, especially in POST and POST3, thus suggesting that the compensation of a baroreflex impairment with a more efficient CBV control and vice versa. The maintenance of this relationship between CV and CBV controls in patients undergoing SAVR could be fundamental to prevent risky situations.Clinical Relevance- After surgical aortic valve replacement an impaired baroreflex control could be compensated by a more efficient cerebral autoregulation.