Anatomy and physiology of the autonomic nervous system: Implication on the choice of diagnostic/monitoring tools in 2023.

The autonomic nervous system (ANS) harmoniously regulates all internal organic functions (heart rate, blood pressure, vasomotion, digestive tract motility, endocrinal secretions) and adapts them to the needs. It's the control of so-called vegetative functions, which allows homeostasis but also allostasis of our body. ANS is divided into two systems often understood as antagonistic and complementary: the sympathetic and the parasympathetic systems. However, we currently know of many situations of co-activation of the two systems. Long seen as acting through "reflex" control loops passing through the integration of peripheral information and the efferent response to the peripheral organ, more recent electrophysiological and brain functional imaging knowledge has been able to identify the essential role of the central autonomic network. This element complicates the understanding of the responses of the reflex loops classically used to identify and quantify dysautonomia. Finding the "ANS" tools best suited for the clinician in their daily practice is a challenge that we will attempt to address in this work.

Optical limiting properties of surface functionalized nanodiamonds probed by the Z-scan method.

This work focuses on the optical limiting behavior of surface modified nanodiamonds (DNDs) namely, amino-terminated DNDs (DND-NH2) and hydrogen-terminated DNDs (DND-H). Their relevant nonlinear optical properties for optical limiting are compared to those of unfunctionalized DNDs. The optical limitation is characterized by means of nonlinear transmittance, Z-scan, and scattered intensity assessments when submitted to a nanosecond pulsed Nd:YAG laser operating at a wavelength of 532 nm. It is stated that the largest nonlinear attenuation is attributed to the DND-H system, whereas the exceedingly low threshold values for optical limiting for the DND-H and the DND-NH2 systems is attributed to their negative electron affinity character (NEA). Using Z-scan experiments, it is shown that nonlinear refraction combined with a significant nonlinear absorption predominates in the DND-H suspension, while the pure thermal origin of the nonlinear refractive index change is conjectured in the case of the DNDs. Besides, an amazing valley to peak profile was measured on DND - NH2indicating an unexpected positive sign of the nonlinear refraction coefficient. In addition, a stronger backscattered intensity signal is highlighted for the unfunctionalized DNDs through nonlinear scattering measurements.

Objective assessment of induced acute pain in neonatology with the Newborn Infant Parasympathetic Evaluation index.

BACKGROUND: Objective tools are needed to improve pain assessment in newborns. The aim of this study was to assess the correlation between the Newborn Infant Parasympathetic Evaluation (NIPE) index and two pain scales during a painful procedure in premature infants. METHOD: Each baby born at least at 26 weeks of gestational age (GA) undergoing a planned painful procedure in the Neonatal Intensive Care Unit (NICU) was eligible. NIPE index, heart rate variability (HRV) indices and Neonatal Acute Pain scale (DAN) were recorded across three periods: the first at rest 5 min before the painful procedure (T1), the second during it (T2) and the third 3 min after the end of it (T3). The Premature Infant Pain Profile-Revised (PIPP-R) pain scale was recorded at T2. RESULTS: Sixty-four recordings were performed in 29 preterm infants (mean GA = 29.9 ± 4.2 weeks). Twenty-eight tachograms were coupled to NIPE for analysis. We did not find a correlation between the NIPE index and DAN and PIPP-R at the pain time T2. Between T1 and T2, heart rate was higher (159 ± 16 vs. 169 ± 12, p < 0.001). Considering the linear HRV indices, we did not observe a modification in parasympathetic or sympathetic activity, while for the nonlinear HRV indices (H exponent, Approximate and conditional Entropy), a significant change towards a loss of physiological chaotic cardiac behaviour was detected. CONCLUSIONS: The NIPE index seems to be not reliable to assess acute pain in the preterm infant, but other HRV indices could be explored as additional tools next to pain scales in NICUs. SIGNIFICANCE: The NIPE monitor was developed for objective pain assessment in neonates based on HFnu variations, but it does not seem reliable enough for assessing acute pain in real time in preterm neonates. Pain assessment in preterm babies still relies on pain scales.

Optical properties of functionalized nanodiamonds.

Detonation nanodiamonds exhibit strong nonlinear optical properties depending on their electronic properties. In the present paper, the nanodiamond functional groups are chemically modified to obtain nanodiamonds with primary amines on their surface. The optical properties of such nanodiamonds placed in water suspensions are studied and compared with the one of classical detonation nanodiamonds. Transmission, scattering and Z-scan experiments are performed for two different wavelengths (532 nm and 1064 nm). A lower threshold for optical limiting associated to more pronounce non-linear optical effects is detected at the wavelength of 1064 nm compared to the one at 532 nm. This effect may be due to a stronger nonlinear backscattering behavior at 1064 nm. Moreover, a striking result obtained from the Z-scan experiments reveals a completely different behavior of the functionalized nanodiamonds for both wavelengths. This result is discussed in regard to the electronic properties of the material and possible charge transfer.

Does an observer's empathy influence my pain? Effect of perceived empathetic or unempathetic support on a pain test.

The physiological and behavioural effects of empathy for other's pain have been widely investigated, while the opposite situation, i.e. the influence on one's pain of empathetic feedback from others, remains largely unexplored. Here, we assessed whether and how empathetic and unempathetic comments from observers modulate pain and associated vegetative reactions. In Study 1, conversations between observers of a pain study were recorded by professional actors. Comments were prepared to be perceived as empathetic, unempathetic or neutral, and were validated in 40 subjects. In a subsequent pain experiment (Study 2), changes in subjective pain and heart rate were investigated in 30 naïve participants who could overhear the empathetic or unempathetic conversations pre-recorded in study 1. Subjective pain was significantly attenuated when hearing empathetic comments, as compared to both unempathetic and neutral conditions, while unempathetic comments failed to significantly modulate pain. Heart rate increased when hearing unempathetic remarks and when receiving pain stimuli, but heart acceleration to nociceptive stimulation was not correlated with pain ratings. These results suggest that empathetic feedback from observers has a positive influence on pain appraisal and that this effect may surpass the negative effect of unempathetic remarks. Negative remarks can either trigger feelings of guilt or induce irritation/anger, with antagonistic effects on pain that might explain inter-individual variation. As in basal conditions heart rate and pain perception are positively correlated, their dissociation here suggests that changes in subjective pain were linked to a cognitive bias rather than changes in sensory input.

Continuous engineering of nano-cocrystals for medical and energetic applications.

Cocrystals, solid mixtures of different molecules on molecular scale, are supposed to be tailor made materials with improved employability compared to their pristine individual components in domains such as medicine and explosives. In medicine, cocrystals are obtained by crystallization of active pharmaceutical ingredients with precisely chosen coformers to design medicaments that demonstrate enhanced stability, high solubility, and therefore high bioavailability and optimized drug up-take. Nanoscaling may further advance these characteristica compared to their micronsized counterparts - because of a larger surface to volume ratio of nanoparticles. In the field of energetic materials, cocrystals offer the opportunity to design smart explosives, combining high reactivity with significantly reduced sensitivity, nowadays essential for a safe manipulation and handling. Furthermore, cocrystals are used in ferroelectrics, non-linear material response and electronic organics. However, state of the art batch processes produce low volume of cocrystals of variable quality and only have produced micronsized cocrystals so far, no nano-cocrystals. Here we demonstrate the continuous preparation of pharmaceutical and energetic micro- and nano-cocrystals using the Spray Flash Evaporation process. Our laboratory scale pilot plant continuously prepared up to 8 grams per hour of Caffeine/Oxalic acid 2:1, Caffeine/Glutaric acid 1:1, TNT/CL-20 1:1 and HMX/Cl-20 1:2 nano- and submicronsized cocrystals.

[Autonomic regulation and bradycardia during the neonatal period]. / Régulation autonomique et bradycardies néonatales.

The high frequency of bradycardia observed during the neonatal period requires cardiac monitoring but also understanding its intrinsic mechanisms, including responsiveness of the autonomic nervous system (ANS). Heart rate variability and spontaneous baroreflex analysis can help understand the autonomic dysregulation of cardiorespiratory control, possibly responsible for sudden infant death. In clinical neonatology practice, neonatal bradycardia does not warrant continuation of monitoring if it remains isolated, asymptomatic, and short (<10 s), followed by a rapid cardiac acceleration indicating an adapted sympathetic response. Further evaluation of ANS responsiveness is possible for newborns including analyzing the complexity of the heart rate and respiratory variability. This allows better targeting children with high risk after discharge. The real-time evaluation of autonomic regulation could become a valuable tool in clinical practice.

Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study.

AIMS: Sleep fragmentation is a landmark of sleep disorders, because microarousals are systematically associated with sympathetic surges (i.e., sympathetic arousals). However, the impact of sympathetic sleep fragmentation on blood pressure (BP) remains understudied. We assessed the relationships between 24 h ambulatory BP monitoring, the autonomic arousal index (AAI) derived from pulse transit time, and heart rate variability indices. We hypothesized that repeated sympathetic arousals during sleep are associated with elevated BP in a large population of elderly volunteers. METHODS AND RESULTS: Volunteer subjects (n = 780, 57.4% women) with a mean age of 68.7 years and free of known sleep-disordered breathing, coronary heart diseases, and neurological disorders underwent polygraphy, 24 h ECG Holter monitoring, and 24 h ambulatory BP monitoring. Multivariate regressions showed that sleep fragmentation, expressed by AAI, was associated with elevated diurnal (P = 0.008) and 24 h (P = 0.005) systolic BP and higher risk for 24 h [odds ratio (OR): 1.70 (1.04-2.80), P = 0.036] systolic hypertension, independently of confounders such as sleep-disordered breathing, body mass index, sex, diabetes, hypercholesterolaemia, and self-reported sleep duration and quality. Increased AAI was associated with higher nocturnal and diurnal low-frequency power (P < 0.001) and low-to-high-frequency ratio (P < 0.001), suggesting nocturnal and diurnal sympathetic overactivity. CONCLUSION: In healthy elderly subjects, repetitive sympathetic arousals during sleep are associated with elevated systolic BP and higher risk of hypertension, after controlling for confounders. Sympathetic overactivity is the proposed underlying mechanism. CLINICAL TRIAL REGISTRATION: NCT00766584 and NCT00759304.

Autonomic pain responses during sleep: a study of heart rate variability.

The autonomic nervous system (ANS) reacts to nociceptive stimulation during sleep, but whether this reaction is contingent to cortical arousal, and whether one of the autonomic arms (sympathetic/parasympathetic) predominates over the other remains unknown. We assessed ANS reactivity to nociceptive stimulation during all sleep stages through heart rate variability, and correlated the results with the presence of cortical arousal measured in concomitant 32-channel EEG. Fourteen healthy volunteers underwent whole-night polysomnography during which nociceptive laser stimuli were applied over the hand. RR intervals (RR) and spectral analysis by wavelet transform were performed to assess parasympathetic (HF(WV)) and sympathetic (LF(WV) and LF(WV)/HF(WV) ratio) reactivity. During all sleep stages, RR significantly decreased in reaction to nociceptive stimulations, reaching a level similar to that of wakefulness, at the 3rd beat post-stimulus and returning to baseline after seven beats. This RR decrease was associated with an increase in sympathetic LF(WV) and LF(WV)/HF(WV) ratio without any parasympathetic HF(WV) change. Albeit RR decrease existed even in the absence of arousals, it was significantly higher when an arousal followed the noxious stimulus. These results suggest that the sympathetic-dependent cardiac activation induced by nociceptive stimuli is modulated by a sleep dependent phenomenon related to cortical activation and not by sleep itself, since it reaches a same intensity whatever the state of vigilance.

Sex differences in obstructive sleep apnoea in an elderly French population.

Obstructive sleep apnoea (OSA) affects females and males differently, and increases in prevalence with age. The aim of the present study was to characterise clinical, anthropometric and polygraphic sex differences in a large elderly OSA population. A total of 641 subjects aged 68 yrs were examined. Measurements of fat mass, using dual-energy X-ray absorptiometry (DEXA) and polygraphy, were obtained in all subjects. An apnoea/hypopnoea index (AHI) of >15 events·h⁻¹ identified the presence of OSA. OSA was diagnosed in 57% of the sample, 34% having a mild form and 23% having an AHI of >30 events·h⁻¹. Females with OSA exhibited a lower AHI, less severe hypoxaemia and greater peripheral fat mass, and frequently reported anxiety and depression. Comparison of females with and without OSA did not reveal significant differences in clinical, anthropometric and DEXA data. After adjustment for body mass index, hypertension, diabetes, smoking, anxiety and depression, logistic regression analysis revealed that the presence of hypertension was significantly associated with OSA risk in females (OR 1.52, p = 0.04). In a general community healthy population, the prevalence of undiagnosed OSA in females increases with age, with a risk similar to that in males. In females, the clinical spectrum, anthropometric data and fat distribution appear to be more sex-related than OSA-dependent. The occurrence of OSA contributes to hypertensive risk in elderly females.

Metabolic syndrome and short-term and long-term heart rate variability in elderly free of clinical cardiovascular disease: the PROOF study.

OBJECTIVE: Autonomic nervous system (ANS) activity decrease has been associated with a higher risk of sudden cardiovascular and cerebrovascular disease. Thus, we explored the relationship between ANS control of the cardiovascular system and metabolic syndrome. METHODS: We analyzed the relationship with both short-term and long-term heart rate variability (HRV) and metabolic syndrome in the cross-sectional PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF) cohort study of 1,011 elderly subjects recruited amongst the inhabitants of the city of Saint Etienne, France, aged 65.6 ± 0.8 years at the inclusion date. Physical examination included measurements of height, weight, systolic and diastolic blood pressure, waist circumference, and biological parameters. HRV variables were measured over 5-min, nighttime, and 24-h periods using Holter monitoring. RESULTS: After adjustment for current type 2 diabetes, depression, and smoking, we found that metabolic syndrome status, high-density lipoprotein cholesterol (HDL-C), and waist circumference were significantly (p < 0.05) associated with total power, very-low frequency, low-frequency/high-frequency (LF/HF) ratio, and normalized LF. HDL-C and metabolic syndrome status were significantly associated with decreased long-term HRV variables. Both nighttime and 24-h HRV showed closer associations with metabolic syndrome than did short-term HRV (5-min). Metabolic syndrome severity was associated with a decrease in both the long-term and short-term HRV variables. CONCLUSIONS: ANS control alteration of the cardiovascular system was more pronounced when evaluated by long-term than short-term HRV recordings, particularly in women.

Association between C-reactive protein and unrecognised sleep-disordered breathing in the elderly.

Elevated levels of C-reactive protein (CRP) have been reported in patients with sleep-disordered breathing (SDB) and may represent an inflammatory marker of cardiovascular risk. However, the association of CRP with SBD in presumed healthy elderly subjects is unknown. In total, 851 (58.5% females) 68-yr-old subjects, who were free of any known cardiac or sleep disorders, were prospectively examined. Subjects underwent unattended polygraphy, and the apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) were assessed. Elevated levels of CRP were found on the morning after the sleep study in patients with more severe SDB. A significant correlation was found between CRP levels, time spent at night with arterial oxygen saturation <90% and ODI. No association was found between CRP levels and AHI. After adjustments for body mass index, smoking status, hypertension, diabetes and dyslipidaemia, a significant association remained between CRP levels and ODI >10 events.h(-1). CRP levels were frequently increased in a large sample of elderly subjects free of major cardiovascular disease. CRP levels were not correlated with the AHI and the indices of sleep fragmentation; the ODI >10 events.h(-1) was the strongest predictor of raised CRP level. The present results suggest that, in the elderly, intermittent hypoxaemia may underlie inflammatory processes leading to cardiovascular morbidity.

Preparation of explosive nanoparticles in a porous chromium(III) oxide matrix: a first attempt to control the reactivity of explosives.

This paper reports the first attempt to control the combustion and the detonation properties of a high explosive through its structure. A porous chromium(III) oxide matrix produced by the combustion of ammonium dichromate was infiltrated by hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The structure of the Cr(2)O(3) matrix was studied by both scanning and transmission electron microscopy (SEM, TEM); the Cr(2)O(3)/RDX nanocomposites were characterized by nitrogen adsorption. A mathematical model based on these techniques was used to demonstrate that the Cr(2)O(3) matrix encloses and stabilizes RDX particles at the nanoscale. The decomposition process of the nanocomposites was investigated by atomic force microscopy (AFM). The reactivity and sensitivity of the nanocomposites were studied by impact and friction tests, differential scanning calorimetry (DSC), time-resolved cinematography and detonation experiments, and were correlated with their structure. The size of RDX nanoparticles and their distribution in the Cr(2)O(3) matrix have an important influence on their reactivity. The reactive properties of nanostructured RDX differ significantly from those of classical micron-sized RDX. For instance, the melting point disappears and the decomposition temperature is significantly lowered. The quantization of the explosive particles in the Cr(2)O(3) matrix decreases the sensitivity to mechanical stress and allows controlling the decomposition mode-i.e. combustion versus detonation.

Analysis of the interbeat interval increment to detect obstructive sleep apnoea/hypopnoea.

The prevalence of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is underestimated and its diagnosis is costly and restricted to specialised sleep laboratories. The frequency component of interbeat interval increment (III) has been proposed as a simple and inexpensive diagnostic tool in OSAHS. In a set of 150 patients with clinically suspected sleep-related breathing disorder, the actual predictive accuracy of the power spectral density of the III of the very low frequencies (%VLFI) was analysed by comparing with the apnoea/hypopnoea index (AHI), as assessed by synchronised polysomnography. OSAHS was defined in 100 patients according to an AHI>or=15 events.h(-1). Receiver operator characteristic curves built for %VLFI confirmed that this variable was able to separate OSAHS positive from OSAHS negative with statistical significance. Using an appropriate threshold (>4%), %VLFI demonstrated a positive predictive value of 80%. Misclassification of false-positive subjects occurred when the patient presented significant sleep discontinuity and sleep fragmentation (sleep fragmentation index>or=50 events.h(-1)) related to insomnia or periodic limb movements. A power spectral density of the interbeat interval increment of very low frequencies>4% allowed correct classification of obstructive sleep apnoea/hypopnoea syndrome when the clinical history suggested sleep-related breathing disorders and when moderate-to-severe cases are considered. Higher power spectral density of the interbeat interval increment of very low frequencies may also indicate disrupted sleep in the absence of clear clinical symptoms of sleep apnoea/hypopnoea syndrome.

Heart rate variability, training variation and performance in elite swimmers.

The aim of the present study was to investigate the relationships between heart rate variability (HRV) changes and both training variations and performances in elite swimmers. A secondary purpose was to measure catecholamine urinary excretion in elite swimmers to validate the HRV indices of sympathetic activity during training. Thirteen swimmers (4 females and 9 males) were tested before and after 4 weeks of intense training (IT) and 3 weeks of reduced training (RT). At the end of each period, the swimmers participated in an official competition of their best event. Individual performances were expressed as percentage of the previous season's best performance. Spectral analysis was used to investigate RR interval variability. HRV indices failed to show any significant changes between the study periods (p>0.05). Pre-IT HF was correlated with performance (r=0.45; p=0.05) and HFnu (r=0.59; p<0.05) during RT. On the other hand, once RT was completed, HFnu was correlated positively to performance (r=0.81; p<0.01) and negatively to fatigue (r=- 0.63; p<0.03). Conversely, the indices of sympathetic activity, i.e., LFnu and LF/HF ratio were inversely related to performance (both r=- 0.81; p<0.01); total fatigue score was correlated to the changes in HFnu (r=- 0.63; p<0.03) and in the LF/HF ratio (r=0.58; p<0.05). Changes in the adrenaline/noradrenaline ratio over the follow-up period were related to the changes in the LF/HF ratio (r=0.45; p<0.03). In highly trained swimmers coping well with a training program, including 4 weeks of IT followed by 3 weeks of RT, HRV indices were unaltered. On the other hand, after the 3 weeks of RT, HFnu was positively related to performance and inversely related to the fatigue score. Thus, elevated initial HF levels could be important in the parasympathetic activity increases during taper and, hence, in swimming performance improvement.

Effect of endurance training on muscle microvascular filtration capacity and vascular bed morphometry in the elderly.

AIM: Exercise training is a strong stimulus for vascular remodelling and could restore age-induced vascular alterations. The purpose of the study was to test the hypothesis that an increase in vascular bed filtration capacity would corroborate microvascular adaptation with training. METHODS: We quantified (1) microvascularization from vastus lateralis muscle biopsy to measure the capillary to fibre interface (LC/PF) and (2) the microvascular filtration capacity (K(f)) in lower limbs through a venous congestion plethysmography procedure. Twelve healthy older subjects (74 +/- 4 years) were submitted to a 14-week training programme during which lower-limbs were trained for endurance exercise. RESULTS: The training programme induced a significant increase in the aerobic exercise capacity of lower limbs (+11% V(O2peak); P < 0.05; +28% Citrate Synthase Activity; P < 0.01). K(f) was largely increased (4.3 +/- 0.9 10(-3) mL min(-1) mmHg(-1) 100 mL(-1) post-training vs. 2.4 +/- 0.8 pre-training, mean +/- SD; P < 0.05) and microvascularization developed as shown by the rise in LC/PF (0.29 +/- 0.06 post- vs. 0.23 +/- 0.06 pre-training; P < 0.05). Furthermore, K(f) and LC/PF were correlated (r = 0.65, P < 0.05). CONCLUSION: These results demonstrated the microvascular adaptation to endurance training in the elderly. The increase in K(f) with endurance training was probably related to a greater surface of exchange with an increased microvessel/fibre interface area. We conclude that measurement of the microvascular filtration rate reflects the change in the muscle exchange area and is influenced by exercise training.

Hot-drawing of single and multiwall carbon nanotube fibers for high toughness and alignment.

We report a new hot-drawing process for treating wet-spun composite fibers made of single- and multiwall carbon nanotubes and poly(vinyl alcohol). As shown in previous reports, untreated composite nanotube fibers exhibit a very large strain-to-failure, and their toughness, which is the energy needed to break the fibers, exceeds that of any other known materials. However, untreated composite nanotube fibers absorb a very small amount of energy at low strain and become degraded in humid conditions. In this work, we use hot-drawing treatments, a concept inspired from textile technologies, to improve the properties of nanotube/PVA fibers. This treatment yields a crystallinity increase of the PVA and an unprecedented degree of alignment of the nanotubes. These structural modifications lead to a markedly improved energy absorption at low strain and make the fibers resistant to moisture. Hot-drawn nanotube/PVA fibers hold great potential for a number of applications such as bulletproof vests, protective textiles, helmets, and so forth.