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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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