Unravelling COVID-19 waves in Rio de Janeiro city: Qualitative insights from nonlinear dynamic analysis.

Since the COVID-19 pandemic was first reported in 2019, it has rapidly spread around the world. Many countries implemented several measures to try to control the virus spreading. The healthcare system and consequently the general quality of life population in the cities have all been significantly impacted by the Coronavirus pandemic. The different waves of contagious were responsible for the increase in the number of cases that, unfortunately, many times lead to death. In this paper, we aim to characterize the dynamics of the six waves of cases and deaths caused by COVID-19 in Rio de Janeiro city using techniques such as the Poincaré plot, approximate entropy, second-order difference plot, and central tendency measures. Our results reveal that by examining the structure and patterns of the time series, using a set of non-linear techniques we can gain a better understanding of the role of multiple waves of COVID-19, also, we can identify underlying dynamics of disease spreading and extract meaningful information about the dynamical behavior of epidemiological time series. Such findings can help to closely approximate the dynamics of virus spread and obtain a correlation between the different stages of the disease, allowing us to identify and categorize the stages due to different virus variants that are reflected in the time series.

Complex nanoemulsion for vitamin delivery: droplet organization and interaction with skin membranes.

Lipid nanoemulsions are promising nanomaterials for drug delivery applications in food, pharmaceutical and cosmetic industries. Despite the noteworthy commercial interest, little is known about their supramolecular organization, especially about how such multicomponent formulations interact with cell membranes. In the present work, coarse-grained molecular dynamics simulations have been employed to study the self-assembly of a 15-component lipid nanoemulsion droplet containing vitamins A and E for skin delivery. Our results display aspects of the unique "onion-like" agglomeration between the chemical constituents in the different layers of the lipid nanodroplet. Vitamin E molecules are more concentrated in the center of the droplet together with other hydrophobic constituents such as the triglycerides with long tails. On the other hand, vitamin A occupies an intermediate layer between the core and the co-emulsifier surface of the nanodroplet, together with lecithin phospholipids. Coarse-grained molecular dynamics simulations were also performed to provide insight into the first steps involved in absorption and penetration of the nanodroplet through skin membrane models, representing an intracellular (hair follicle infundibulum) and intercellular pathway (stratum corneum) through the skin. Our data provide a first view on the complex organization of commercial nanoemulsion and its interaction with skin membranes. We expect our results to open the way towards the rational design of such nanomaterials.

Extended Central Tendency Measure and difference plot for heart rate variability analysis.

Heart rate variability (HRV) is a non-invasive alternative to analyze the role of the autonomic nervous system (ANS) on heart functioning. Many tools have been developed to analyze collected cardiac data. Among them, the Central Tendency Measure (CTM) is a quantitative method for variability analysis of RR intervals. The values of the CTM must be between 0 and 1 (inclusive) for different radius, which follows the intrinsic characteristics of each time series. Using the conventional CTM, the successive differences of the time series may be calculated, and it can classify and differentiate the disturbances in the ANS involving HRV. This method was extended (e-CTM) to analyze the differences between RR interval time series. In this extension, a new parameter is added, which allows analysis of long time intervals, instead of successive and adjacent RR intervals. The ability of the e-CTM to differentiate the groups of the RR interval time series was verified with 145 RR interval time series divided into three groups: subjects with congestive heart failure, healthy subjects, and nurses during one hour of their workday. Results evidence that the new parameter added differentiates the group with pathology (and subsequent impairment of ANS) and group under stress at work (temporary impairment of ANS). These results suggest that the e-CTM is capable of detection long-term variations in the HRV according to the ANS impairment.

Analysis of molecular markers as predictive factors of lymph node involvement in breast carcinoma.

Nodal status is the most significant independent prognostic factor in breast cancer. Identification of molecular markers would allow stratification of patients who require surgical assessment of lymph nodes from the large numbers of patients for whom this surgical procedure is unnecessary, thus leading to a more accurate prognosis. However, up to now, the reported studies are preliminary and controversial, and although hundreds of markers have been assessed, few of them have been used in clinical practice for treatment or prognosis in breast cancer. The purpose of the present study was to determine whether protein phosphatase Mg2+/Mn2+ dependent 1D, ß-1,3-N-acetylglucosaminyltransferase, neural precursor cell expressed, developmentally down-regulated 9, prohibitin, phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5), phosphatidylinositol-5-phosphate 4-kinase type IIα, TRF1-interacting ankyrin-related ADP-ribose polymerase 2, BCL2 associated agonist of cell death, G2 and S-phase expressed 1 and PAX interacting protein 1 genes, described as prognostic markers in breast cancer in a previous microarray study, are also predictors of lymph node involvement in breast carcinoma Reverse transcription-quantitative polymerase chain reaction analysis was performed on primary breast tumor tissues from women with negative lymph node involvement (n=27) compared with primary tumor tissues from women with positive lymph node involvement (n=23), and was also performed on primary tumors and paired lymph node metastases (n=11). For all genes analyzed, only the PIK3R5 gene exhibited differential expression in samples of primary tumors with positive lymph node involvement compared with primary tumors with negative lymph node involvement (P=0.0347). These results demonstrate that the PIK3R5 gene may be considered predictive of lymph node involvement in breast carcinoma. Although the other genes evaluated in the present study have been previously characterized to be involved with the development of distant metastases, they did not have predictive potential.

DFT:B3LYP/3-21G theoretical insights on the confocal Raman experimental observations in skin dermis of healthy young, healthy elderly, and diabetic elderly women.

In the confocal Raman spectra of skin dermis, the band area in the spectral region of proline and hydroxyproline varies according to the age and health condition of the volunteers, classified as healthy young women, healthy elderly women, and diabetic elderly women. Another observation refers to the intensity variation and negative Raman shift of the amide I band. To understand these effects, we adopted a model system using the DFT/B3LYP:3-21G procedure, considering the amino acid chain formed by glycine, hydroxyproline, proline, and alanine, which interacts with two and six water molecules. Through these systems, polarizability variations were analyzed to correlate its values with the observed Raman intensities of the three groups of volunteers and to assign the vibrational spectra of the skin dermis. As a way to correlate other experimental trends, we propose a model of chemical reaction of water interchange between the bonding amino acids, in which water molecules are attached with glucose by hydrogen bonds. The theoretical results are in accordance with the observed experimental trends.

Assessment of heart rate variability by application of central tendency measure.

The heart rate variability (HRV) is an indicator of the subject homeostasis alterations. For a healthy individual, the HRV shows a nonlinear behavior, thus requiring a nonlinear approach to provide additional information about HRV dynamics. In this work, the nonlinear techniques, central tendency measure (CTM) and second-order difference plot, are applied to HRV analysis using the successive difference of RR intervals in a time series. In total are analyzed 170 tachograms collected by Polar monitor and then classified into three groups according to a cardiologist: healthy young adults, adults in preoperative evaluation for coronary artery bypass grafting for severe coronary disease and premature newborns. This approach identified the tachograms with high and low variability, which demonstrates the ability of CTM to classify and quantitatively characterize cardiac RR intervals.

Triplet entropy analysis of hemagglutinin and neuraminidase sequences measures influenza virus phylodynamics.

The influenza virus has been a challenge to science due to its ability to withstand new environmental conditions. Taking into account the development of virus sequence databases, computational approaches can be helpful to understand virus behavior over time. Furthermore, they can suggest new directions to deal with influenza. This work presents triplet entropy analysis as a potential phylodynamic tool to quantify nucleotide organization of viral sequences. The application of this measure to segments of hemagglutinin (HA) and neuraminidase (NA) of H1N1 and H3N2 virus subtypes has shown some variability effects along timeline, inferring about virus evolution. Sequences were divided by year and compared for virus subtype (H1N1 and H3N2). The nonparametric Mann-Whitney test was used for comparison between groups. Results show that differentiation in entropy precedes differentiation in GC content for both groups. Considering the HA fragment, both triplet entropy as well as GC concentration show intersection in 2009, year of the recent pandemic. Some conclusions about possible flu evolutionary lines were drawn.