Statistical Validation of Cardiovascular Digital Biomarkers Towards Monitoring the Cardiac Risk in COPD: A Lyfas Case Study

Background: Mobile health (mHealth) is gaining popularity due to its pervasiveness. Lyfas is a smartphone-based optical biomarker instrument catering to mHealth. It captures the Pulse Rate Variability (PRV) and its associated digital biomarkers from the index finger capillary circulation using the principle of arterial photoplethysmography. PRV surrogates for the Cardiovascular Autonomic Modulation (CvAM) and provides a snapshot of psychophysiological homeostasis of the body. Objective: The paper investigates the roles of (a) physiological factors, e.g., Age, Duration of illness, Heart Rate (HR), Respiration Rate (RR), SpO2 level, and (b) popular digital biomarkers, such as SDNN, LF/HF, RMSSD, pNN50, SD1/SD2 to evaluate the cardiac risk. The paper hypothesizes that low FEV1, which is another physiological factor, plays a critical role in defining such risk. Method: A total of 50 males and females each, suffering from Chronic Obstructive Pulmonary Disease (COPD) took the Lyfas test after appropriate ethical measures. Data, thus collected by Lyfas had been statistically analyzed using histogram plots and Kolmogorov-Smirnov test for normality check, Pearson's Correlations (PC) to measure the strength of associations, and linear regressions to test the goodness of fit of the model. Results: Positive PCs are noted between (a) RMSSD and SDNN ('very high'-females: 0.86 and males: 0.91), (b) pNN50 and RMSSD (PC: moderate 0.46), (c) pNN50 and SDNN (PC: moderate 0.44), (d) Duration of illness and Age ('high'-females: 0.71 and males: 0.77), and (e) Age and RR ('high'-females: 0.67, males: 0.53). Negative PC is noted between (a) LF/HF and FEV1 ('moderately high'-males 0.42) and (b) LF/HF and SpO2 ('moderately high'-males 0.30). Although the R2 values are not so encouraging (most are < 0.5), yet, the models are statistically significant (p-values 0.0336; CI 95%). Conclusion: The paper concludes that Lyfas may be used to predict the cardiac risk in COPD patients based on the LF/HF values correlated to SpO2 and FEV1 levels.

CODE-SWITCHING IN THE CONTEXT OF UDMURT-RUSSIAN BILINGUALISM (BASED ON VERB FORMS)

On the one hand, code switching as a linguistic phenomenon is a speaker’s transition from one language to another in the process of verbal communication, depending on the conditions of communication; on the other hand, it is the interaction of structures and structural elements of two languages. Its implementation in speech is due to a number of reasons: extralinguistic (external), intralinguistic (linguistic proper), psycho-physiological. The main purpose of this article is to identify the structural types as well as lexical and semantic characteristics of code switching, based on verb forms in the speech of native Udmurt speakers in the context of Udmurt-Russian bilingualism. In the course of the study, it was found that, in contrast to the nominal parts of speech, verbs are less susceptible to the phenomenon of code-switching. The matrix (Udmurt) language is characterized by three types of inclusion of verb forms from the donor language: a) the use of an auxiliary verb (light verb strategy); b) indirect insertion, characterized by the attachment of special morphological markers; c) semantic borrowing. In terms of lexical and semantic characteristics, the phenomenon of code switching in the context of Udmurt-Russian bilingualism is most typical of verbal units reflecting the practical and spiritual (mental, emotional, volitional) activities of people. This proves the important role of the psycho-physiological factor in the emergence of switching codes.

Treatment of Polarized Cystic Fibrosis Airway Cells With HGF Prevents VX-661-Rescued F508del-CFTR Destabilization Caused by Prolonged Co-exposure to VX-770

Cystic fibrosis (CF), the most common inherited disease in Caucasians, is caused by mutations in CFTR, the most frequent of which is F508del. F508del causes ER retention and degradation of the mutant CFTR protein, but also defective channel gating and decreased half-life at the plasma membrane. Despite the recent successes with small-molecule CFTR modulator drugs, the folding-corrector/gating-potentiator drug combinations approved for CF individuals carrying F508del-CFTR have sometimes produced severe side effects. Previously, we showed that a prolonged, 15-days treatment of polarized bronchial epithelial monolayers with the VX-809+VX-770 combination resulted in epithelial dedifferentiation effects that we found were caused specifically by VX-809. Moreover, prolonged VX-770 exposure also led to the destabilization of VX-809-rescued F508del-CFTR. Notably, co-treatment with the physiological factor HGF prevented VX-809-mediated epithelial differentiation and reverted the destabilizing effect of VX-770 on VX-809-rescued CFTR. Here, we show that prolonged treatment with VX-661, a second-generation corrector developed based on VX-809 structure, does not perturb epithelial integrity of polarized bronchial epithelial monolayers. Yet, its efficacy is still affected by co-exposure to VX-770, the potentiator present in all VX-661-containing combination therapies approved in the United States and Europe for treatment of F508del-CFTR carriers. Importantly, we found that co-treatment with HGF still ameliorated the impact of VX-770 in F508del-CFTR functional rescue by VX-661, without increasing cell proliferation (Ki-67) or altering the overall expression of epithelial markers (ZO-1, E-cadherin, CK8, CK18). Our findings highlight the importance of evaluating the cellular effects of prolonged exposure to CFTR modulators and suggest that the benefits of adding HGF to current combination therapies should be further investigated.

Heteroblastic Foliage Affects the Accumulation of Non-Structural Carbohydrates and Biomass in Pinus massoniana (Lamb.) Seedlings

Pines have heteroblastic foliage (primary and secondary needles) during seedling stage, but how heteroblastic foliage affects carbon storage and biomass accumulation, contributing to seedling quality, is unclear. We investigated the influences of heteroblastic foliage on photosynthetic physiological characteristics, non-structural carbohydrate (NSC) and biomass accumulation in current-year seedlings; the key factors determining biomass accumulation were mainly determined by principal component screening, Spearman correlation, and path analysis. The results indicated that (1) primary needles have high photosynthetic pigments (chlorophyll a and total chlorophyll), net photosynthetic rates (Pn), the potential maximum photochemical efficiency (Fv/Fm), and leaf instantaneous water use efficiency (WUEi), whereas higher non-photochemical quenching (NPQ) suggested that sudden light increases induce the initiation of quenching mechanism in primary needles; additionally, secondary needles had a lower transpiration rate (Tr), limiting stomata (Ls), and light saturation point. (2) Secondary needles promoted soluble sugar (fructose and glucose) increases in leaves compared to that of primary needles and increased the leaf biomass accumulation (from 47.06% to 54.30%), enhancing the overall ability of photosynthetic organs; additionally, secondary needles can enhance the proportion of starch storage in the roots, and NSC accumulation was significantly increasing in the seedling leaves and roots. (3) Photosynthetic pigments (carotenoids, chlorophyll a, and total chlorophyll) had direct positive effects on primary needle seedling (PNS) biomass and promoted biomass by indirectly increasing soluble sugar synthesis in the stems. The Pn was the main physiological factor determining PNS biomass accumulation. In addition, the WUEi, Ls, and NPQ had direct negative effects on PNS biomass accumulation, inhibiting photosynthesis to limit seedling growth. Considering the functional traits in heteroblastic foliage is necessary when assessing different leaf types of Pinus massoniana (Lamb.) seedlings, in particular those threats implicated in light, water, and temperature relations. Our results can be beneficial to guide the establishment of seedling management and afforestation measures.

Effect of Exercise on Brain Health: The Potential Role of Lactate as a Myokine

It has been well established in epidemiological studies and randomized controlled trials that habitual exercise is beneficial for brain health, such as cognition and mental health. Generally, it may be reasonable to say that the physiological benefits of acute exercise can prevent brain disorders in late life if such exercise is habitually/chronically conducted. However, the mechanisms of improvement in brain function via chronic exercise remain incompletely understood because such mechanisms are assumed to be multifactorial, such as the adaptation of repeated acute exercise. This review postulates that cerebral metabolism may be an important physiological factor that determines brain function. Among metabolites, the provision of lactate to meet elevated neural activity and regulate the cerebrovascular system and redox states in response to exercise may be responsible for exercise-enhanced brain health. Here, we summarize the current knowledge regarding the influence of exercise on brain health, particularly cognitive performance, with the underlying mechanisms by means of lactate. Regarding the influence of chronic exercise on brain function, the relevance of exercise intensity and modality, particularly high-intensity interval exercise, is acknowledged to induce “metabolic myokine” (i.e., lactate) for brain health.

The Evolution of Hemocyanin Genes in Caenogastropoda: Gene Duplications and Intron Accumulation in Highly Diverse Gastropods

Hemocyanin is the oxygen transport protein of most molluscs and represents an important physiological factor that has to be well-adapted to their environments because of the strong influences of abiotic factors on its oxygen affinity. Multiple independent gene duplications and intron gains have been reported for hemocyanin genes of Tectipleura (Heterobranchia) and the caenogastropod species Pomacea canaliculata, which contrast with the uniform gene architectures of hemocyanins in Vetigastropoda. The goal of this study was to analyze hemocyanin gene evolution within the diverse group of Caenogastropoda in more detail. Our findings reveal multiple gene duplications and intron gains and imply that these represent general features of Apogastropoda hemocyanins. Whereas hemocyanin exon–intron structures are identical within different Tectipleura lineages, they differ strongly within Caenogastropoda among phylogenetic groups as well as between paralogous hemocyanin genes of the same species. Thus, intron accumulation took place more gradually within Caenogastropoda but finally led to a similar consequence, namely, a multitude of introns. Since both phenomena occurred independently within Heterobranchia and Caenogastropoda, the results support the hypothesis that introns may contribute to adaptive radiation by offering new opportunities for genetic variability (multiple paralogs that may evolve differently) and regulation (multiple introns). Our study indicates that adaptation of hemocyanin genes may be one of several factors that contributed to the evolution of the large diversity of Apogastropoda. While questions remain, this hypothesis is presented as a starting point for the further study of hemocyanin genes and possible correlations between hemocyanin diversity and adaptive radiation.

Features of ozone effect on oxygen-dependent processes in the blood under hypoxic conditions

Introduction. Ozone is a physiological factor that can change hemoglobin oxygen affinity and the formation of gaseous transmitters (NO, H2S). The aim is to study the effect of ozone with gaseous transmitters donors on oxygen-dependent processes in the blood under hypoxic conditions in vitro. Materials and methods. Blood samples were divided into 6 groups of 3 ml each. Groups 2, 4, 5, 6 were pretreated with a deoxygenating gas mixture (5.5 % CO2; 94.5 % N2). In groups 3, 4, 5, 6, ozonized isotonic sodium chloride solution (with an ozone concentration of 6 mg/l) was added, and in groups 5 and 6, the donors of gas transmitters nitroglycerin and sodium hydrosulfide, respectively, were additionally introduced. Results. Pre-deoxygenation reduces the effect of ozone on oxygen transport in the blood. Nitroglycerin prevents this effect. The action of ozone under hypoxic conditions leads to an increase of content of NO3-/NO2- and H2S, and combination with nitroglycerin and sodium hydrosulfide increase these parameters. Deoxygenation due to ozone reduces parameters of lipid peroxidation (malonic dialdehyde, diene conjugates), retinol and α-tocopherol, and the same result in the nitroglycerin group. Conclusion. Under hypoxic conditions, a decrease in the effect of ozone on oxygen-dependent processes is reported. Nitroglycerin reduces its manifestation, while sodium hydrosulfide does not have a similar effect.

Serotonin regulates hepcidin expression via a gut-liver axis

Liver hepcidin, is well recognized as the central hormone of systemic iron regulation. Although serotonin is most recognized as a brain neurotransmitter, prodigious quantities are synthesized in gut enterochromaffin cells and several lines of evidence, also identified the gut as an essential sensor and regulator of iron homeostasis. Using a mouse model deficient for peripheral serotonin (Tph1 KO), we identified gut-derived serotonin as a key physiological factor in hepcidin regulation. Serotonin represses hepcidin's through a 5HT2B receptor-dependent pathway, independently of any other known hepcidin regulators, including bone marrow signals. This regulation is conserved in humans and shows physiological significance as a negative correlation between serotonin and hepcidin levels was observed in a cohort of healthy individuals. Moreover, in pathological situation such as acute heart failure, where iron deficiency has a negative prognostic impact, we provide evidence that an increase in serotonin level seems necessary to repress hepcidin level, to increase iron availability.

Impact of Water Temperature on Heart Rate Variability during Bathing

Background: Heart rate variability (HRV) is affected by many factors. This paper aims to explore the impact of water temperature (WT) on HRV during bathing. Methods: The bathtub WT was preset at three conditions: i.e., low WT (36–38 °C), medium WT (38–40 °C), and high WT (40–42 °C), respectively. Ten subjects participated in the data collection. Each subject collected five electrocardiogram (ECG) recordings at each preset bathtub WT condition. Each recording was 18 min long with a sampling rate of 200 Hz. In total, 150 ECG recordings and 150 WT recordings were collected. Twenty HRV features were calculated using 1-min ECG segments each time. The k-means clustering analysis method was used to analyze the rough trends based on the preset WT. Analyses of the significant differences were performed using the multivariate analysis of variance of t-tests, and the mean and standard deviation (SD) of each HRV feature based on the WT were calculated. Results: The statistics show that with increasing WT, 11 HRV features are significantly (p < 0.05) and monotonously reduced, four HRV features are significantly (p < 0.05) and monotonously rising, two HRV features are rising first and then reduced, two HRV features (fuzzy and approximate entropy) are almost unchanged, and vLF power is rising. Conclusion: The WT has an important impact on HRV during bathing. The findings in the present work reveal an important physiological factor that affects the dynamic changes of HRV and contribute to better quantitative analyses of HRV in future research works.