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.

Effectiveness of Led Photobiomodulation Therapy on Treatment With Knee Osteoarthritis: A Rat Study.

OBJECTIVE: The present study aimed to evaluate the effectiveness of photobiomodulation therapy by light-emitting diode on osteoarthritis treatment in the knees of rats. DESIGN: Twenty male Wistar rats were randomly assigned into two experimental groups: OAC: animals subjected to induction of osteoarthritis, without therapeutic intervention and the group OAL: animals subjected to induction of osteoarthritis treated with light-emitting diode photobiomodulation therapy (850 nm, 200 mW, 6 J). RESULTS: The results of gait analysis showed no statistical difference between the groups. The histological findings showed that the OAL group presented abnormal chondrocyte orientation, yet with less irregularities along fibrillation and the joint tissue. Thus, it presented a lower degenerative process when evaluated by the Osteoarthritis Research Society International. Likewise, in the immunohistochemical analysis, the OAL group showed higher collagen 2 and transforming growth factor ß immunoexpression when compared with the OAC group. CONCLUSIONS: Given the above, it is possible to suggest that the photobiomodulation therapy by light-emitting diode had positive effects on the expression of extracellular matrix proteins responsible for synthesis of articular tissue.

Can ethanol affect the cell structure? A dynamic molecular and Raman spectroscopy study.

The role that tobacco consumption plays in the etiology of oral cancer carcinogenesis, and of alcohol consumption acting as a co-factor, have been well established. However, in recent years, the contribution of alcohol consumption alone to oral cancer has been proposed. In fact, a high percentage of patients who develop oral cancer have both habits (tobacco and alcohol consumption), and other small patient groups only consume alcohol or do not have any other identifiable bad habits. In the present study we demonstrate, using a combination of dynamic molecular modelling and Raman spectroscopy, that ethanol has a significant effect on oral cells in vitro, mainly interacting with the lipids of the cell membrane, changing their conformation. Thus, it is possible to conclude that ethanol can affect the cell permeability, and by consequence serve as a possible trigger in oral carcinogenesis.

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.

Raman spectroscopic analysis of oral cells in the high wavenumber region.

Raman spectroscopy can provide a molecular-level signature of the biochemical composition and structure of cells with submicrometer spatial resolution and could be useful to monitor changes in composition for early stage and non-invasive cancer diagnosis, both ex-vivo and in vivo. In particular, the fingerprint spectral region (400-1800cm-1) has been shown to be very promising for optical biopsy purposes. However, limitations for discrimination of dysplastic and inflammatory processes based on the fingerprint region have been demonstrated. In addition, the Raman spectral signal of dysplastic cells is one important source of misdiagnosis of normal versus pathological tissues. The high wavenumber region (2800-3600cm-1) provides more specific information based on NH, OH and CH vibrations and can be used to identify the subtle changes which could be important for discrimination of samples. In this study, we demonstrate the potential of the high-wavenumber spectral region in this context by collecting Raman spectra of nucleolus, nucleus and cytoplasm from oral epithelial cancer (SCC-4) and dysplastic (DOK) cell lines and from normal oral epithelial primary cells, in vitro, in water immersion, which were then analyzed by principal components analysis as a method to discriminate the spectra. Analysis was performed before and after digital subtraction of the bulk water signal. In the normal cell line, the three subcellular regions are well differentiated before water subtraction, although the discrimination of the two nuclear regions is less well defined after water subtraction. Comparing the respective subcellular regions of the three cell lines, before water subtraction, the cell lines can be discriminated using sequential PCA and Feature Discriminant Analysis with up to ~100% sensitivity and 97% specificity for the cytoplasm, which is improved to 100% sensitivity and 99% specificity for the nucleus. The results are discussed in terms of discrimination comparing the CH vibrational modes of nucleic acids, proteins and lipids. The potential role of the OH vibrations, considering free water and confined water, in the discrimination of cell cultures and pathological processes are also discussed.

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.

In vivo confocal Raman spectroscopy and molecular dynamics analysis of penetration of retinyl acetate into stratum corneum.

OBJECTIVE: The purpose of this study is to elucidate the behavior of retinyl acetate in penetrating human skin without the presence of enhancers by using confocal Raman spectroscopy and molecular dynamics simulation. METHODS: In this study, in vivo confocal Raman spectroscopy was combined with molecular dynamics simulation to investigate the transdermal permeation of the aqueous suspension of retinyl acetate. RESULTS: Permeation was measured after 30min, and retinyl acetate was found up to 20µm deep inside the stratum corneum. The delivery of retinyl acetate inside a skin membrane model was studied by molecular dynamics. The membrane model that was used represented normal young skin containing a lipid bilayer with 25% ceramide, 36% fatty acid, 30% cholesterol, and 6% cholesterol sulfate. CONCLUSION: Spectroscopy data indicate that retinyl acetate permeates into the stratum corneum. Molecular dynamics data showed that retinyl acetate permeates in the membrane model and that their final location is deep inside the lipid bilayer. We showed, for the first time, a correlation between Raman permeation data and computational data.

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.

Application of an automatic adaptive filter for Heart Rate Variability analysis.

The presence of artifacts and noise effects in temporal series can seriously hinder the analysis of Heart Rate Variability (HRV). The tachograms should be carefully edited to avoid erroneous interpretations. The physician should carefully analyze the tachogram in order to detect points that might be associated with unlikely biophysical behavior and manually eliminate them from the data series. However, this is a time-consuming procedure. To facilitate the pre-analysis of the tachogram, this study uses a method of data filtering based on an adaptive filter which is quickly able to analyze a large amount of data. The method was applied to 229 time series from a database of patients with different clinical conditions: premature newborns, full-term newborns, healthy young adults, adults submitted to a very-low-calorie diet, and adults under preoperative evaluation for coronary artery bypass grafting. This proposed method is compared to the demanding conventional method, wherein the corrections of occasional ectopic beats and artifacts are usually manually executed by a specialist. To confirm the reliability of the results obtained, correlation coefficients were calculated, using both automatic and manual methods of ltering for each HRV index selected. A high correlation between the results was found, with highly significant p values, for all cases, except for some parameters analyzed in the premature newborns group, an issue that is thoroughly discussed. The authors concluded that the proposed adaptive filtering method helps to efficiently handle the task of editing temporal series for HRV analysis.

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.