Lack of effect of dietary nucleotide supplementation on erythrocyte 2,3-diphosphoglycerate concentration. A study on preterm neonates.

BACKGROUND: Recently we demonstrated an increased 2,3-diphosphoglycerate (2,3-DPG) erythrocyte concentration in rat pups subjected to nucleotide-enriched artificial feeding. DESIGN: The present study was carried out to test the hypothesis that a possible increase in 2,3-DPG concentration can also be obtained in human neonates who are fed nucleotide-enriched formula. Preterm neonates born or referred to the neonatal intensive care unit of the G. Gaslini Hospital, Genoa University, with a gestational age >30 weeks and <37 weeks were enrolled in our randomized trial. Recruitment took place within 48-72 hours from birth. Only newborns of mothers deciding not to breast-feed were eligible to be randomized for the supplemented group (FN) or non-supplemented group (RF). Breast-fed newborns were considered the control group (C). The study window (for supplementation and blood samples) was restricted to the first two weeks following birth (from the 2nd (t1) to the 16th (t2) day of life). At the end of our study, only 21 neonates were eligible for statistical analysis. RESULTS: The stimulating action of dietary nucleotides on 2,3-DPG concentration failed to be demonstrated; increases in 2,3-DPG concentration that were observed in newborns fed with nucleotide supplemented formula (FN) were comparable to those observed in newborns fed with regular formula (RF) and breast-fed newborns. CONCLUSIONS: The EC recommendation for the amount of nucleotides allowed in formula milk does not seem to be high enough to have positive effects on 2,3-DPG synthesis. Whether this possible 'pharmacological' effect can be achieved by a higher intake of ingested nucleotides and/or a change in the proportions of single nucleotides contained in milk formulas remain interesting end points to be elucidated.     

Human milk and formulae: neurotrophic and new biological factors

Mother milk is widely accepted to be a unique product believed to contain biological factors involved in the regulation of newborn optimal growth including brain when compared to milk-formula milks. In this setting, there is growing evidence that in milk-formula neuro-oxidative stress biomarkers, neurotrophic proteins and calcium binding proteins, known to be involved in a cascade of events leading to brain, cardiac and vascular development/damage, are to date lacking or at a lower concentration than breast milk. Therefore, this review is aimed at offering additional insights to the role in human milk of some selected biomarkers such as: i) neurotrophic factors such as Activin A; ii) Calcium binding protein such as S100B and, iii) heat shock protein known to be involved in oxidative stress response (namely hemeoxygenase-1, HO-1 or Heat shock Protein 32, HSP32).     

Pharmacological closure of patent ductus arteriosus: effects on pulse pressure and on endothelin-1 and vasopressin excretion

Widened pulse pressure is a classic sign of significant left-to-right shunting patent ductus arteriosus (PDA), but little evidence supports this statement in the early life of premature infants with respiratory distress syndrome (RDS) needing nonsteroidal anti-inflammatory drugs (NSAIDs), the pharmacological treatment for PDA. Pulse pressure and urinary endothelin-1 (ET-1) and arginine vasopressin (AVP) vasoactive factors involved in the transitional circulation were measured before and after the NSAIDs treatment of 46 RDS premature infants receiving either ibuprofen (n = 22) or indomethacin (n = 24), with 28 responders and 18 nonresponders to the first NSAIDs course. We found that following pharmacological PDA closure, systolic and diastolic blood pressure significantly increased, maintaining a stable pulse pressure. However, when pharmacological closure failed, the trend (nonsignificant) was for a more consistent increase in systolic than in diastolic blood pressure, which determined a statistically significant widening pulse pressure. In addition, urinary ET-1 excretion rates decreased significantly after PDA closure, whereas persistent more aggressive pharmacological therapy failed. Urinary AVP excretion rates decreased insignificantly after therapy, uninfluenced by the efficacy of the drugs. We concluded that widened pulse pressure is a clinical sign of failed PDA pharmacological closure in RDS premature infants. ET-1 levels remain elevated when NSAIDs fail to interrupt left-to-right PDA shunting that complicates recovery from RDS.     

Agar Biopolymer Films for Biodegradable Packaging: A Reference Dataset for Exploring the Limits of Mechanical Performance

This article focuses on agar biopolymer films that offer promise for developing biodegradable packaging, an important solution for reducing plastics pollution. At present there is a lack of data on the mechanical performance of agar biopolymer films using a simple plasticizer. This study takes a Design of Experiments approach to analyze how agar-glycerin biopolymer films perform across a range of ingredients concentrations in terms of their strength, elasticity, and ductility. Our results demonstrate that by systematically varying the quantity of agar and glycerin, tensile properties can be achieved that are comparable to agar-based materials with more complex formulations. Not only does our study significantly broaden the amount of data available on the range of mechanical performance that can be achieved with simple agar biopolymer films, but the data can also be used to guide further optimization efforts that start with a basic formulation that performs well on certain property dimensions. We also find that select formulations have similar tensile properties to thermoplastic starch (TPS), acrylonitrile butadiene styrene (ABS), and polypropylene (PP), indicating potential suitability for select packaging applications. We use our experimental dataset to train a neural network regression model that predicts the Young’s modulus, ultimate tensile strength, and elongation at break of agar biopolymer films given their composition. Our findings support the development of further data-driven design and fabrication workflows.     

Cardiac sympathetic-vagal activity initiates a functional brain–body response to emotional arousal

A century-long debate on bodily states and emotions persists. While the involvement of bodily activity in emotion physiology is widely recognized, the specificity and causal role of such activity related to brain dynamics has not yet been demonstrated. We hypothesize that the peripheral neural control on cardiovascular activity prompts and sustains brain dynamics during an emotional experience, so these afferent inputs are processed by the brain by triggering a concurrent efferent information transfer to the body. To this end, we investigated the functional brain–heart interplay under emotion elicitation in publicly available data from 62 healthy subjects using a computational model based on synthetic data generation of electroencephalography and electrocardiography signals. Our findings show that sympathovagal activity plays a leading and causal role in initiating the emotional response, in which ascending modulations from vagal activity precede neural dynamics and correlate to the reported level of arousal. The subsequent dynamic interplay observed between the central and autonomic nervous systems sustains the processing of emotional arousal. These findings should be particularly revealing for the psychophysiology and neuroscience of emotions.

“What Is an Emotion?” by William James (1), published more than a century ago, started the scientific debate on the nature of emotions. However, a shared and definitive theory of emotions is not in place yet, and the very definition of emotions and their nature is still a matter of debate. While more “classical” theories point to emotions as “the functional states of the brain that provide causal explanations of certain complex behaviors—like evading a predator or attacking prey” (2), other theories suggest how they are constructions of the world, not reactions to it (3). Namely, emotions are internal states constructed on the basis of previous experiences as predictive schemes to react to external stimuli.The role of bodily activity in emotions is often questioned. Despite the vast literature showing bodily correlates with emotions, a long-lasting debate about the relationship between bodily states and emotions persists (4). For instance, a feeling is defined as the subjective metarepresentation and labeling of physiological changes (such as an increase in heart rate, the increase of blood pressure, or changes in peristalsis) (5) that are strictly related to the body state on the one hand and to emotions on the other. To this extent, emotions are complex psychological phenomena in which feelings are interpreted and labeled. In a particular psychopathological condition known as alexithymia, individuals experience difficulties in experiencing and understanding emotions to various degrees (6). Indeed, some of these patients can perceive the physical changes connected to a feeling but are unable to label it as emotion, so that emotional experience is described only as its physical counterpart [e.g., described an experience as “I have my heart beating too fast” instead of “I’m fearful” (7)]. From a biological point of view the way in which physical changes become feelings and emotions is based on the interplay between the central and the autonomic nervous systems.The central nervous system (CNS) communicates with the autonomic nervous system (ANS) through interoceptive neural circuits that contribute to physiological functions beyond homeostatic control, from the emotional experience and the genesis of feelings (8) to decision making (9, 10). The debate about the role of the ANS in emotions can be condensed into two views: specificity or causation (4). The specificity view is related to the James–Lange theory, which states that bodily responses precede emotions’ central processing, meaning that bodily states would be a response to the environment, followed by an interpretation carried out by the CNS that would result in the feeling felt. However, causation theories represent an updated view of the James–Lange theory, suggesting that peripheral changes influence the conscious emotional experience; from a biological point of view this may reflect the fact that autonomic nervous signals from the body do influence perceptual activity in the brain (11, 12). In this regard, subjective perception may be influenced or shaped by ascending communication from visceral inputs to the brain (13–15).Functional models of CNS and ANS interplay have described bidirectional dynamics in emotions (16–18). In particular, the functional brain–heart interplay (BHI) involves brain structures that comprise the central autonomic network (CAN), which has been described as being in charge of autonomic control (19, 20). Moreover, the default mode network (DMN) has been found to be involved in autonomic control (21) and tasks of self-related cognition and interoception (22, 23), suggesting that the DMN participates in both ascending and descending communications with the heart. Finally, the constructed emotion theory suggests how DMN together with other intrinsic networks is crucial in the genesis of emotion and emotional experience (3).Psychophysiological studies have uncovered several correlates of different autonomic signals in the brain during emotional experiences (24–27). To understand these correlations and the functional interactions between the heart and brain, various signal processing methods have been proposed to investigate functional BHI through noninvasive recordings (28). The study of emotions using these methods comprises the analysis of heartbeat-evoked potentials (29), nonlinear couplings (30), and information transfer modeling (31). However, the causative role of bodily inputs remains unknown (4) and, more specifically, the temporal and causal links between cortical and peripheral neural dynamics in both ascending and descending directions, i.e., from the brain to the body and from the body to the brain, are still to be clarified.In this study, we take a step forward in answering these scientific questions and investigate whether peripheral neural dynamics play a causal role in the genesis of emotions. We applied a mathematical model of functional BHI based on synthetic data generation (SDG) (32), estimating the directionality of the functional interplay using simultaneous electroencephalography (EEG) and electrocardiography (ECG) recordings gathered from healthy subjects undergoing emotion elicitations with video clips, the publicly available DEAP and MAHNOB datasets (33, 34). ECG series were analyzed to derive heart-rate variability (HRV) series, which result from the concurrent activity of the sympathetic and parasympathetic (vagal) branches of the ANS acting to regulate the heartbeat. We hypothesize that, from a neurobiological point of view, feelings and subsequent emotional experiences arise from the mutual interplay between brain and body, particularly in which the CNS integrates the afferent ANS information outflow, namely from-heart-to-brain interplay, which actually triggers a cascade of cortical neural activations that, in turn, modulate directed neural control onto the heart, namely from brain-to-heart interplay.     

A nucleic acid amplification test‐based strategy does not help inform return to work for healthcare workers with COVID‐19

ObjectiveThe objective of this study is to assess the utility of a nucleic acid amplification test‐based approach to shorten isolation of healthcare workers (HCWs) with COVID‐19 in the setting of the highly transmissible omicron variant.MethodsBetween December 24, 2021, and January 5, 2022, HCWs who tested positive for SARS‐CoV‐2 were retested with PCR at least 5 days since onset of symptoms.ResultsForty‐six sequential fully COVID‐19 vaccinated HCWs who had tested positive for SARS‐CoV‐2 underwent follow‐up testing. All the samples were confirmed as omicron variants and only four (8.7%) were negative in the follow‐up test performed at a median of 6 (range 5–12) since onset of symptoms.ConclusionsImplementation of a test‐based strategy is logistically challenging, increases costs, and did not lead to shorter isolation in our institution.