Risk factors contributing to infection with SARS-CoV-2 are modulated by sex.

Throughout the early stages of the COVID-19 pandemic in Mexico (August-December 2020), we closely followed a cohort of n = 100 healthcare workers. These workers were initially seronegative for Immunoglobulin G (IgG) antibodies against SARS-CoV-2, the virus that causes COVID-19, and maintained close contact with patients afflicted by the disease. We explored the database of demographic, physiological and laboratory parameters of the cohort recorded at baseline to identify potential risk factors for infection with SARS-CoV-2 at a follow-up evaluation six months later. Given that susceptibility to infection may be a systemic rather than a local property, we hypothesized that a multivariate statistical analysis, such as MANOVA, may be an appropriate statistical approach. Our results indicate that susceptibility to infection with SARS-CoV-2 is modulated by sex. For men, different physiological states appear to exist that predispose to or protect against infection, whereas for women, we did not find evidence for divergent physiological states. Intriguingly, male participants who remained uninfected throughout the six-month observation period, had values for mean arterial pressure and waist-to-hip ratio that exceeded the normative reference range. We hypothesize that certain risk factors that worsen the outcome of COVID-19 disease, such as being overweight or having high blood pressure, may instead offer some protection against infection with SARS-CoV-2.

Achalasia alters physiological networks depending on sex.

Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. While the infection is eventually resolved, genetically susceptible individuals may still be at risk of developing achalasia. This study aimed to determine whether immunological and physiological networks differ between male and female patients with achalasia. This cross-sectional study included 189 preoperative achalasia patients and 500 healthy blood donor volunteers. Demographic, clinical, laboratory, immunological, and tissue biomarkers were collected. Male and female participants were evaluated separately to determine the role of sex. Correlation matrices were constructed using bivariate relationships to generate complex inferential networks. These matrices were filtered based on their statistical significance to identify the most relevant relationships between variables. Network topology and node centrality were calculated using tools available in the R programming language. Previous occurrences of chickenpox, measles, and mumps infections have been proposed as potential risk factors for achalasia, with a stronger association observed in females. Principal component analysis (PCA) identified IL-22, Th2, and regulatory B lymphocytes as key variables contributing to the disease. The physiological network topology has the potential to inform whether a localized injury or illness is likely to produce systemic consequences and the resulting clinical presentation. Here we show that immunological involvement in achalasia appears localized in men because of their highly modular physiological network. In contrast, in women the disease becomes systemic because of their robust network with a larger number of inter-cluster linkages.

Frailty Syndrome as a Transition from Compensation to Decompensation: Application to the Biomechanical Regulation of Gait.

Most gait parameters decrease with age and are even more importantly reduced with frailty. However, other gait parameters exhibit different or even opposite trends for aging and frailty, and the underlying reason is unclear. Literature focuses either on aging, or on frailty, and a comprehensive understanding of how biomechanical gait regulation evolves with aging and with frailty seems to be lacking. We monitored gait dynamics in young adults (19-29 years, n = 27, 59% women), middle-aged adults (30-59 years, n = 16, 62% women), and non-frail (>60 years, n = 15, 33% women) and frail older adults (>60 years, n = 31, 71% women) during a 160 m walking test using the triaxial accelerometer of the Zephyr Bioharness 3.0 device (Zephyr Technology, Annapolis, MD, USA). Frailty was evaluated using the Frail Scale (FS) and the Clinical Frailty Scale (CFS). We found that in non-frail older adults, certain gait parameters, such as cadence, were increased, whereas other parameters, such as step length, were decreased, and gait speed is maintained. Conversely, in frail older adults, all gait parameters, including gait speed, were decreased. Our interpretation is that non-frail older adults compensate for a decreased step length with an increased cadence to maintain a functional gait speed, whereas frail older adults decompensate and consequently walk with a characteristic decreased gait speed. We quantified compensation and decompensation on a continuous scale using ratios of the compensated parameter with respect to the corresponding compensating parameter. Compensation and decompensation are general medical concepts that can be applied and quantified for many, if not all, biomechanical and physiological regulatory mechanisms of the human body. This may allow for a new research strategy to quantify both aging and frailty in a systemic and dynamic way.

Ecological and Convergent Validity of Experimentally and Dynamically Assessed Capacity for Social Contingency Detection Using the Perceptual Crossing Experiment in Adolescence.

The Perceptual Crossing Experiment (PCE) captures the capacity for social contingency detection using real-time social interaction dynamics but has not been externally validated. We tested ecological and convergent validity of the PCE in a sample of 208 adolescents from the general population, aged 11 to 19 years. We expected associations between PCE performance and (a) quantity and quality of social interaction in daily life, using Experience Sampling Methodology (ESM; ecological validity) and (b) self-reported social skills using a questionnaire (convergent validity). We also expected PCE performance to better explain variance in ESM social measures than self-reported social skills. Multilevel analyses showed that only self-reported social skills were positively associated with social experience of company in daily life. These initial results do not support ecological and convergent validity of the PCE. However, fueled by novel insights regarding the complexity of capturing social dynamics, we identified promising methodological advances for future validation efforts.

Chronotropic Response and Heart Rate Variability before and after a 160 m Walking Test in Young, Middle-Aged, Frail, and Non-Frail Older Adults.

The frailty syndrome is characterized by a decreased capacity to adequately respond to stressors. One of the most impaired physiological systems is the autonomous nervous system, which can be assessed through heart rate (HR) variability (HRV) analysis. In this article, we studied the chronotropic response (HR and HRV) to a walking test. We also analyzed HRV indices in rest as potential biomarkers of frailty. For this, a 160 m-walking test and two standing rest tests (before and after the walking) were performed by young (19−29 years old, n = 21, 57% women), middle-aged (30−59 years old, n = 16, 62% women), and frail older adults (>60 years old, n = 28, 40% women) and non-frail older adults (>60 years old, n = 15, 71% women), classified with the FRAIL scale and the Clinical Frailty Scale (CFS). Frequency domain parameters better allowed to distinguish between frail and non-frail older adults (low-frequency power LF, high-frequency power HF (nu), LF/HF ratio, and ECG-derived respiration rate EDR). Frail older adults showed an increased HF (nu) and EDR and a reduced LF (nu) and LF/HF compared to non-frail older adults. The increase in HF (nu) could be due to a higher breathing effort. Our results showed that a walk of 160 m is a sufficient cardiovascular stressor to exhibit an attenuated autonomic response in frail older adults. Several HRV indices showed to be potential biomarkers of frailty, being LF (nu) and the time required to reach the maximum HR the best candidates.

High Incidence Rate of SARS-CoV-2 Infection in Health Care Workers at a Dedicated COVID-19 Hospital: Experiences of the Pandemic from a Large Mexican Hospital.

Health care workers (HCW) are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The incidence of SARS-CoV-2 infection in HCW has been examined in cross-sectional studies by quantitative polymerase chain reaction (qPCR) tests, which may lead to underestimating exact incidence rates. We thus investigated the incidence of SARS-CoV-2 infection in a group of HCW at a dedicated coronavirus disease 2019 (COVID-19) hospital in a six-month follow-up period. We conducted a prospective cohort study on 109 participants of both sexes working in areas of high, moderate, and low SARS-CoV-2 exposure. qPCR tests in nasopharyngeal swabs and anti-SARS-CoV-2 IgG serum antibodies were assessed at the beginning and six months later. Demographic, clinical, and laboratory parameters were analyzed according to IgG seropositivity by paired Student's T-test or the chi-square test. The incidence rate of SARS-CoV-2 infection was considerably high in our cohort of HCW (58%), among whom 67% were asymptomatic carriers. No baseline risk factors contributed to the infection rate, including the workplace. It is still necessary to increase hospital safety procedures to prevent virus transmissibility from HCW to relatives and non-COVID-19 patients during the upcoming waves of contagion.

Physiological Network Is Disrupted in Severe COVID-19.

The human body is a complex system maintained in homeostasis thanks to the interactions between multiple physiological regulation systems. When faced with physical or biological perturbations, this system must react by keeping a balance between adaptability and robustness. The SARS-COV-2 virus infection poses an immune system challenge that tests the organism's homeostatic response. Notably, the elderly and men are particularly vulnerable to severe disease, poor outcomes, and death. Mexico seems to have more infected young men than anywhere else. The goal of this study is to determine the differences in the relationships that link physiological variables that characterize the elderly and men, and those that characterize fatal outcomes in young men. To accomplish this, we examined a database of patients with moderate to severe COVID-19 (471 men and 277 women) registered at the "Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán" in March 2020. The sample was stratified by outcome, age, and sex. Physiological networks were built using 67 physiological variables (vital signs, anthropometric, hematic, biochemical, and tomographic variables) recorded upon hospital admission. Individual variables and system behavior were examined by descriptive statistics, differences between groups, principal component analysis, and network analysis. We show how topological network properties, particularly clustering coefficient, become disrupted in disease. Finally, anthropometric, metabolic, inflammatory, and pulmonary cluster interaction characterize the deceased young male group.

A non-parametric model: free analysis of actigraphic recordings of acute insomnia patients.

Both parametric and non-parametric approaches to time-series analysis have advantages and drawbacks. Parametric methods, although powerful and widely used, can yield inconsistent results due to the oversimplification of the observed phenomena. They require the setting of arbitrary constants for their creation and refinement, and, although these constants relate to assumptions about the observed systems, it can lead to erroneous results when treating a very complex problem with a sizable list of unknowns. Their non-parametric counterparts, instead, are more widely applicable but present a higher detrimental sensitivity to noise and low density in the data. For the case of approximately periodic phenomena, such as human actigraphic time series, parametric methods are widely used and concepts such as acrophase are key in chronobiology, especially when studying healthy and diseased human populations. In this work, we present a non-parametric method of analysis of actigraphic time series from insomniac patients and healthy age-matched controls. The method is fully data-driven, reproduces previous results in the context of activity offset delay and, crucially, extends the concept of acrophase not only to circadian but also for ultradian spectral components.

Dependence of Heart Rate Variability Indices on the Mean Heart Rate in Women with Well-Controlled Type 2 Diabetes.

Heart rate variability (HRV) is a method used to evaluate the presence of cardiac autonomic neuropathy (CAN) because it is usually attributed to oscillations in cardiac autonomic nerve activity. Recent studies in other pathologies suggest that HRV indices are strongly related to mean heart rate, and this does not depend on autonomic activity only. This study aimed to evaluate the correlation between the mean heart rate and the HRV indices in women patients with well-controlled T2DM and a control group. HRV was evaluated in 19 T2DM women and 44 healthy women during basal supine position and two maneuvers: active standing and rhythmic breathing. Time-domain (SDNN, RMSSD, pNN20) and frequency-domain (LF, HF, LF/HF) indices were obtained. Our results show that meanNN, age, and the maneuvers are the main predictors of most HRV indices, while the diabetic condition was a predictor only for pNN20. Given the known reduced HRV in patients with T2DM, it is clinically important that much of the HRV indices are dependent on heart rate irrespective of the presence of T2DM. Moreover, the multiple regression analyses evidenced the multifactorial etiology of HRV.

Sex Differences in the Physiological Network of Healthy Young Subjects.

Within human physiology, systemic interactions couple physiological variables to maintain homeostasis. These interactions change according to health status and are modified by factors such as age and sex. For several physiological processes, sex-based distinctions in normal physiology are present and defined in isolation. However, new methodologies are indispensable to analyze system-wide properties and interactions with the objective of exploring differences between sexes. Here we propose a new method to construct complex inferential networks from a normalization using the clinical criteria for health of physiological variables, and the correlations between anthropometric and blood tests biomarkers of 198 healthy young participants (117 women, 81 men, from 18 to 27 years old). Physiological networks of men have less correlations, displayed higher modularity, higher small-world index, but were more vulnerable to directed attacks, whereas networks of women were more resilient. The networks of both men and women displayed sex-specific connections that are consistent with the literature. Additionally, we carried out a time-series study on heart rate variability (HRV) using Physionet's Fantasia database. Autocorrelation of HRV, variance, and Poincare's plots, as a measure of variability, are statistically significant higher in young men and statistically significant different from young women. These differences are attenuated in older men and women, that have similar HRV distributions. The network approach revealed differences in the association of variables related to glucose homeostasis, nitrogen balance, kidney function, and fat depots. The clusters of physiological variables and their roles within the network remained similar regardless of sex. Both methodologies show a higher number of associations between variables in the physiological system of women, implying redundant mechanisms of control and simultaneously showing that these systems display less variability in time than those of men, constituting a more resilient system.

Cardiovascular dysautonomia in Achalasia Patients: Blood pressure and heart rate variability alterations.

Achalasia is a disease characterized by the inability to relax the esophageal sphincter due to a degeneration of the parasympathetic ganglion cells located in the wall of the thoracic esophagus. Achalasia has been associated with extraesophageal dysmotility, suggesting alterations of the autonomic nervous system (ANS) that extend beyond the esophagus. The purpose of the present contribution is to investigate whether achalasia may be interpreted as the esophageal manifestation of a more generalized disturbance of the ANS which includes alterations of heart rate and/or blood pressure. Therefore simultaneous non-invasive records of the heart inter-beat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) of 14 patients (9 female, 5 male) with achalasia were compared with the records of 34 rigorously screened healthy control subjects (17 female, 17 male) in three different conditions: supine, standing up, and controlled breathing at 0.1 Hz, using a variety of measures in the time and spectral domains. Significant differences in heart rate variability (HRV) and blood pressure variability (BPV) were observed which seem to be due to cardiovagal damage to the heart, i.e., a failure of the ANS, as expected according to our hypothesis. This non-invasive methodology can be employed as an auxiliary clinical protocol to study etiology and evolution of achalasia, and other pathologies that damage ANS.

Heart Rate Variability and Psychometric Analysis in Patients with Hyperactive Heart Fire Syndrome.

Background: Hyperactive heart fire syndrome is characterized by anxiety, insomnia, dream-disturbed sleep, tongue ulcers, heat in the hands, and palpitations. However, syndrome differentiation is often subjective due to a lack of objective, quantifiable variables. Objectives: To identify changes in heart rate variability (HRV) and psychometric analysis in patients with hyperactive heart fire syndrome. Methods: Healthy controls (n = 33) were compared to patients with hyperactive heart fire syndrome (n = 48) from the Integrative University Clinic of the State University of Ecatepec Valley (CIU-UNEVE). Physiological outcome measures included heart rate (HR), the standard deviation of the normal-to-normal heartbeat intervals (SDNN), low (LF) and high frequency (HF) power, and the LF/HF ratio. Psychometric outcome measures included the Athens Insomnia Scale (AIS) and the Hamilton Anxiety Rating Scale (HARS). Results: Compared to controls, hyperactive heart fire patients had higher HR (9.6 ± 2.62%), LF (22 ± 4.21%) and LF/HF ratio (23 ± 3.14%), and lower SDNN (21 ± 2.33%) and HF (18 ± 4.61%). Patients showed increased anxiety, both with somatic (33 ± 11.2%) and psychic symptoms (39 ± 10.5%) with more difficulty falling asleep (47 ± 9.9%) and diurnal impact of sleep (31 ± 9.6%). Conclusion: Hyperactive heart fire patients may have a sympathovagal imbalance due to a reduced parasympathetic tone and/or adominant sympathetic tone, which may be at the origin of the observed symptoms of insomnia and anxiety.

The Feeling Is Mutual: Clarity of Haptics-Mediated Social Perception Is Not Associated With the Recognition of the Other, Only With Recognition of Each Other.

The enactive theory of perception hypothesizes that perceptual access to objects depends on the mastery of sensorimotor contingencies, that is, on the know-how of the regular ways in which changes in sensations depend on changes in movements. This hypothesis can be extended into the social domain: perception of other minds is constituted by mastery of self-other contingencies, that is, by the know-how of the regular ways in which changes in others' movements depend on changes in one's movements. We investigated this proposal using the perceptual crossing paradigm, in which pairs of players are required to locate each other in an invisible one-dimensional virtual space by using a minimal haptic interface. We recorded and analyzed the real-time embodied social interaction of 10 pairs of adult participants. The results reveal a process of implicit perceptual learning: on average, clarity of perceiving the other's presence increased over trials and then stabilized. However, a clearer perception of the other was not associated with correctness of recognition as such, but with both players correctly recognizing each other. Furthermore, the moments of correct mutual recognition tended to happen within seconds. The fact that changes in social experience can only be explained by the successful performance at the level of the dyad, and that this veridical mutual perception tends toward synchronization, lead us to hypothesize that integration of neural activity across both players played a role.

The Impact of Education and Age on Metabolic Disorders.

Metabolic disorders, such as obesity, elevated blood pressure, dyslipidemias, insulin resistance, hyperglycemia, and hyperuricemia have all been identified as risk factors for an epidemic of important and widespread chronic-degenerative diseases, such as type 2 diabetes and cardiovascular disease, that constitute some of the world's most important public health challenges. Their increasing prevalence can be associated with an aging population and to lifestyles within an obesogenic environment. Taking educational level as a proxy for lifestyle, and using both logistic and linear regressions, we study the relation between a wide set of metabolic biomarkers, and educational level, body mass index (BMI), age, and sex as correlates, in a population of 1,073 students, academic and non-academic staff at Mexico's largest university (UNAM). Controlling for BMI and sex, we consider educational level and age as complementary measures-degree and duration-of exposure to metabolic insults. Analyzing the role of education across a wide spectrum of educational levels (from primary school to doctoral degree), we show that higher education correlates to significantly better metabolic health when compared to lower levels, and is associated with significantly less risk for waist circumference, systolic blood pressure, glucose, glycosylated hemoglobin, triglycerides, high density lipoprotein and metabolic syndrome (all p < 0.05); but not for diastolic blood pressure, basal insulin, uric acid, low density lipoprotein, and total cholesterol. We classify each biomarker, and corresponding metabolic disorder, by its associated set of statistically significant correlates. Differences among the sets of significant correlates indicate various aetiologies and the need for targeted population-specific interventions. Thus, variables strongly linked to educational level are candidates for lifestyle change interventions. Hence, public policy efforts should be focused on those metabolic biomarkers strongly linked to education, while adopting a different approach for those biomarkers not linked as they may be poor targets for educational campaigns.

Investigating real-time social interaction in pairs of adolescents with the Perceptual Crossing Experiment.

The study of real-time social interaction provides ecologically valid insight into social behavior. The objective of the current research is to experimentally assess real-time social contingency detection in an adolescent population, using a shortened version of the Perceptual Crossing Experiment (PCE). Pairs of 148 adolescents aged between 12 and 19 were instructed to find each other in a virtual environment interspersed with other objects by interacting with each other using tactile feedback only. Across six rounds, participants demonstrated increasing accuracy in social contingency detection, which was associated with increasing subjective experience of the mutual interaction. Subjective experience was highest in rounds when both participants were simultaneously accurate in detecting each other's presence. The six-round version yielded comparable social contingency detection outcome measures to a ten-round version of the task. The shortened six-round version of the PCE has therefore enabled us to extend the previous findings on social contingency detection in adults to an adolescent population, enabling implementation in prospective research designs to assess the development of social contingency detection over time.

Physiological Network From Anthropometric and Blood Test Biomarkers.

Currently, research in physiology focuses on molecular mechanisms underlying the functioning of living organisms. Reductionist strategies are used to decompose systems into their components and to measure changes of physiological variables between experimental conditions. However, how these isolated physiological variables translate into the emergence -and collapse- of biological functions of the organism as a whole is often a less tractable question. To generate a useful representation of physiology as a system, known and unknown interactions between heterogeneous physiological components must be taken into account. In this work we use a Complex Inference Networks approach to build physiological networks from biomarkers. We employ two unrelated databases to generate Spearman correlation matrices of 81 and 54 physiological variables, respectively, including endocrine, mechanic, biochemical, anthropometric, physiological, and cellular variables. From these correlation matrices we generated physiological networks by selecting a p-value threshold indicating statistically significant links. We compared the networks from both samples to show which features are robust and representative for physiology in health. We found that although network topology is sensitive to the p-value threshold, an optimal value may be defined by combining criteria of stability of topological features and network connectedness. Unsupervised community detection algorithms allowed to obtain functional clusters that correlate well with current medical knowledge. Finally, we describe the topology of the physiological networks, which lie between random and ordered structural features, and may reflect system robustness and adaptability. Modularity of physiological networks allows to explore functional clusters that are consistent even when considering different physiological variables. Altogether Complex Inference Networks from biomarkers provide an efficient implementation of a systems biology approach that is visually understandable and robust. We hypothesize that physiological networks allow to translate concepts such as homeostasis into quantifiable properties of biological systems useful for determination and quantification of health and disease.

Indicators of vulnerability associated with less healthy circadian rhythms in undergraduate medical interns.

To evaluate the association between circadian health parameters and psychological and biological vulnerability, a cross-sectional study was conducted with 15 undergraduate medical interns using the Brief Resilience Scale, the Mini International Neuropsychiatric Interview, and an ambulatory circadian monitoring device. Circadian Health construct was confirmed by factor analysis. Vulnerability factors (history of depression and low resilience) were associated to lower circadian health of motor activity and temperature rhythms. The findings suggest that not only being depressed but also having had depressive episodes in the past, as well as having low resilience, are associated with chronodisruption, and may increase the risk for developing new episodes of depression.

Changes in Heart Rate Variability in Patients with Spleen-Qi Deficiency Syndrome.

Many functional diseases are related to dysautonomia, and heart rate variability has been used to assess dysautonomia. However, heart rate variability has not been studied in Spleen-Qi deficiency syndrome (SQDS). Healthy volunteers (n = 37) and patients with SQDS (n = 67), recruited from the Clinic of the State University of Ecatepec Valley were included in the study. Outcome measures were average heart rate, standard deviation of the normal-to-normal heartbeat intervals, low frequency (LF), high frequency (HF) power, and the LF/HF ratio. Also, intestinal peristalsis, gastrointestinal symptoms (GSs), fatigue, and level of attention were measured. Standard deviation of the normal-to-normal heartbeat intervals (17 ± 2.3%) and HF (14 ± 3.1%) were lower in SQDS patients (17 ± 1.3%) than in healthy volunteers. SQDS patients had higher heart rate, LF power, LF/HF ratio, and fatigue scores (9.6 ± 1.12%, 16 ± 2.1%, 22 ± 3.8%, and 21 ± 4.1%). The fatigue correlated positively with the LF/HF ratio and negatively with HF power. The SQDS group had lower concentration performance (16.2 ± 1.9%) in the d2 test. The intestinal peristalsis showed a reduction (15 ± 1.3%) as compared with control. GS score and peristalsis correlated negatively with HF. Our results suggest that the pathology of SDQS could be associated with a low vagal tone which causes a decrease in peristalsis, increased fatigue, reduced attention, and appearance of GSs.

A physicist's view of homeostasis: how time series of continuous monitoring reflect the function of physiological variables in regulatory mechanisms.

OBJECTIVE: Homeostasis is one of the key concepts of physiology and the basis to understand chronic-degenerative disease and human ageing, but is difficult to quantify in clinical practice. The variability of time series resulting from continuous and non-invasive physiological monitoring is conjectured to reflect the underlying homeostatic regulatory processes, but it is not clear why the variability of some variables such as heart rate gives a favourable health prognosis whereas the variability of other variables such as blood pressure implies an increased risk factor. The purpose of the present contribution is to quantify homeostasis using time-series analysis and to offer an explanation for the phenomenology of physiological time series. APPROACH: Within the context of network physiology, which focusses on the interactions between various variables at multiple scales of time and space, it may be understood that different physiological variables may play distinct roles in their respective regulatory mechanisms. In the present contribution, we distinguish between regulated variables, such as blood pressure or core temperature, and physiological responses, such as heart rate and skin temperature. MAIN RESULTS: We give evidence that in optimal conditions of youth and health the former are characterized by Gaussian statistics, low variability and represent the stability of the internal environment, whereas the latter are characterized by non-Gaussian distributions, large variability and reflect the adaptive capacity of the human body; in the adverse conditions of ageing and/or disease, adaptive capacity is lost and the variability of physiological responses is diminished, and as a consequence the stability of the internal environment is compromised and its variability increases. SIGNIFICANCE: Time-series analysis allows one to quantify homeostasis in the optimal conditions of youth and health and the degradation of homeostasis or homeostenosis in the adverse conditions of ageing and/or disease, and may offer an alternative approach to diagnosis in clinical practice.