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The presence of moisturizing substances and lipid substances determines the integrity of the epidermis cells and their barrier functions because it protects the interior of the body against environmental changes: temperature, humidity, ultraviolet radiation, pollution, and the effects of detergents. In this study, we performed a non-invasive, preliminary evaluation of the effects of a biphasic facial skin care product containing plant oils, hyaluronic acid, glycerin, and panthenol on skin hydration levels and transepidermal water loss compared to a control group using only shea butter. The topical care product formed as a two-phase emulsion was tested. The research was carried out with the use of the scientific multi-probe MPA system by Courage + Khazaka Electronic MmbH, which included Tewameter®TM 300 and Corneometer® CM 825. The DermaMed DRAMINSKI ultrasound scanner was used for ultrasound diagnostics. The results were statistically analyzed using multivariate ANOVA. The obtained results indicate an improvement in the level of hydration of the stratum corneum and a reduction in trans-epidermal water loss compared to the control group (p = 0.039). Active ingredients contained in the serum, such as vegetable oils from raspberry seeds, sunflower seeds, carrots, russet rose and jojoba oil, glycerin, panthenol, and sodium hyaluronate can improve stratum corneum hydration in the test subjects after a 14-day application test. The research confirms the validity of the use of diagnostic equipment and statistical testing in the potential assessment of the effectiveness of the tested topical care products.

Facial makeup cosmetics are commonly used products that are applied to the skin, and their ingredients come into contact with it for many years. Consequently, they should only contain substances that are considered safe or used within an allowable range of established concentrations. According to current European laws, all cosmetics approved for use should be entirely safe for their users, and the responsibility for this lies with manufacturers, distributors, and importers. However, the use of cosmetics can be associated with undesirable effects due to the presence of certain chemical substances. An analysis of 50 random facial makeup cosmetics commercially available on the European Union market and manufactured in six European countries was carried out, concerning the presence of substances with potential carcinogenic properties, as described in recent years in the literature. Nine types of facial makeup cosmetics were selected, and their compositions, as declared on the labels, were analyzed. The carcinogens were identified with information present in the European CosIng database and according to the Insecticide Resistance Action Committee’s (IRAC) classification. As a result, the following potential carcinogens were identified: parabens (methylparaben, propylparaben, butylparaben, and ethylparaben), ethoxylated compounds (laureth-4, lautreth-7, or ethylene glycol polymers known as PEG), formaldehyde donors (imidazolidinyl urea, quaternium 15, and DMDM hydantoin), and ethanolamine and their derivatives (triethanolamine and diazolidinyl urea), as well as carbon and silica. In conclusion, all of the analyzed face makeup cosmetics contain potential carcinogenic substances. The literature review confirmed the suppositions regarding the potential carcinogenic effects of selected cosmetic ingredients. Therefore, it seems necessary to carry out studies on the long-term exposure of compounds present in cosmetics and perhaps introduce stricter standards and laws regulating the potential presence of carcinogens and their activity in cosmetics.

In the present article, we consider blow-up phenomena appearing in k-equivariant harmonic map heat flow from to a unit sphere : Here the scalar variable u stands for latitudinal angle on from the north pole to the south pole . The integer corresponds to the eigenvalues associated to eigenmaps , that is, harmonic maps with constant energy density. We prove constructively the existence of asymptotically non-self-similar blow-up solutions with precise description of their local space-time profiles. The blow-up solutions arise from, depending on the combination of d and k, two different approximations of the nonlinear term: either through a Dirac mass supported at the origin or via a Taylor expansion around equator map . Transition of the blow-up mechanisms arises, accordingly.

Background Nanocarriers for antibacterial drugs became hopeful tools against the increasing resistance of bacteria to antibiotics. This work focuses on a comprehensive study of the applicability and therapeutic suitability of dermal carbopol-based hydrogels containing chloramphenicol carried by various nanoparticles (AuNPs and SiNPs). Methods The different forms of carbopol-based drugs for dermal use were obtained. Five different concentrations of chloramphenicol and two types of nanoparticles (silica and gold) in carbopol-based ointments were tested. The influence of different carbopol formulations with nanocarriers on the rheological properties as well as the release profile of active substances and bacteriostatic activity on five reference strains were determined. Results The properties of the obtained hydrogels were compared to a commercial formulation, and finally it was possible to obtain a formulation that allowed improved antimicrobial activity over a commercially available detreomycin ointment while reducing the concentration of the antibiotic. Conclusion The work indicates that it is possible to reduce the concentration of chloramphenicol by four times while maintaining its bacteriostatic activity, which can improve the patient’s safety profile while increasing the effectiveness of the therapy. Graphical abstract

The intestinal microbiota is a complex and diverse ecological community that fulfills multiple functions and substantially impacts human health. Despite its plasticity, unfavorable conditions can cause perturbations leading to so-called dysbiosis, which have been connected to multiple diseases. Unfortunately, understanding the mechanisms underlying the crosstalk between those microorganisms and their host is proving to be difficult. Traditionally used bioinformatic tools have difficulties to fully exploit big data generated for this purpose by modern high throughput screens. Machine Learning (ML) may be a potential means of solving such problems, but it requires diligent application to allow for drawing valid conclusions. This is especially crucial as gaining insight into the mechanistic basis of microbial impact on human health is highly anticipated in numerous fields of study. This includes oncology, where growing amounts of studies implicate the gut ecosystems in both cancerogenesis and antineoplastic treatment outcomes. Based on these reports and first signs of clinical benefits related to microbiota modulation in human trials, hopes are rising for the development of microbiome-derived diagnostics and therapeutics. In this mini-review, we're inspecting analytical approaches used to uncover the role of gut microbiome in immune checkpoint therapy (ICT) with the use of shotgun metagenomic sequencing (SMS) data.

We consider co-rotational wave maps from (1+3)-dimensional Minkowski space into the three-sphere. This model exhibits an explicit blowup solution, and we prove the asymptotic nonlinear stability of this solution in the whole space under small perturbations of the initial data. The key ingredient is the introduction of a novel coordinate system that allows one to track the evolution past the blowup time and almost up to the Cauchy horizon of the singularity. As a consequence, we also obtain a result on continuation beyond blowup.

Two Demodex species (eyelash mites)—D. folliculorum and D brevis—are believed to be associated with human skin and eye diseases. However, the clinical significance of infection with Demodex species remains controversial. The aim of this study was to estimate the prevalence of ocular demodicosis in patients with blepharitis as compared with the prevalence in the healthy population in Poland. This case-control prospective study was carried out from 2007 to 2016. The enrolled patients (668) were divided into 2 groups: the study group, comprising 553 patients with blepharitis (349 women and 204 men, aged 17–88 years), and the control group, comprising 115 healthy volunteers without a history of ocular pathologies (78 women and 37 men, aged 17–88 years). A sample of 10 eyelashes was taken aseptically from each eye of the examined person and later studied under a light microscope. Demodex species were found in 62.4% (345/544) of the patients in the study group and in 24.3% (28/100) of the controls (P = .001, OR = 0.006). The overall prevalence was 55.8% (373/668) in all the examined participants. The presence of Demodex infection increased with age in both groups. No association of Demodex infection with gender was found (119/204 vs 226/349; P > .05, OR 1.086). A high mean number of mites was present more frequently in patients aged older than 50 years and in those who complained especially about itching (P < .05). The prevalence of ocular demodicosis is significantly correlated with blepharitis and increases with age.

During the pharmacological therapy of specific diseases, drugs are used which, with other preparations or foods, can create connections, in many cases changing or even blocking their action. On the other hand, the use of unsuitable polymers as excipients may result in drug-polymer incompatibilities. Interactions consisting mainly of the occurrence of the adsorption phenomenon and on the formation of complex bonds that reduce the effect of the drugs are of particular importance. The aim of the study was to investigate whether the active substance atorvastatin is incompatible with dietary supplements containing chitosan. The phenomenon of the adsorption of the drug was examined using a static model of a pharmaceutical gastrointestinal tract, in the concentration range generally ingested in a single dose. Measurement results of the amount of bound drug were used to determine the average percentage of adsorbed drug dose. The results of the study prove that the anticholinesterase drug is adsorbed on chitosan in the pH ranges used, and that the binding capacity depends on the chitosan variety, which indirectly affects the reaction of the environment. It was observed that the average size of sorption depending on the chitosan variety ranged from 38% to 86%. The fact that the lowest value of adsorption was at pH 6.4 can be explained by the chemical properties of chitosan, which shows a charge only at pH >6.7. Under such conditions, the phenomenon of electrostatic adsorption may occur in relation to the healing substances of weak acids. At a pH above 7.6, corresponding to the intestinal fluid-filled intestine, the mean sorption for the highest dose of chitosan was from 38–86%. The increase in the adsorbed amount of anticholinesterase drugs on the polymer along with the increase in pH from 7.6 to 8.0 can be explained by the chitosan swelling properties, which increase with an increase in the pH. As a result, the specific surface area of the polymer and its sorption capacity increase. Based on the above considerations, it can be concluded that there is an antagonistic interaction between the drug and the polymer studied, which involves the adsorption of a drug from this group on the polymer (chitosan) and a decrease in its bioavailability.

We prove the existence of a (spectrally) stable self-similar blow-up solution f 0 to the heat flow for corotational harmonic maps from to the three-sphere. In particular, our result verifies the spectral gap conjecture stated by one of the authors and lays the groundwork for the proof of the nonlinear stability of f 0. At the heart of our analysis lies a new existence result of a monotone self-similar solution f 0. Although solutions of this kind have already been constructed before, our approach reveals substantial quantitative properties of f 0, leading to the stability result. A key ingredient is the use of interval arithmetic: a rigorous computer-assisted method for estimating functions. It is easy to verify our results by robust numerics but the purpose of the present paper is to provide mathematically rigorous proofs.

We consider equivariant wave maps from $\mathbb{R}^{d+1}$ to $\mathbb{S}^d$ in supercritical dimensions $3\leq d\leq 6$. Using mixed numerical and analytic methods, we show that the threshold of blowup is given by the codimension-one stable manifold of a self-similar solution with one instability., 11 pages, 3 figures

The substantial increase in the efficiency of organic solar cells achieved in recent years would not have been possible without work on the synthesis of new materials and understanding the relationship between the morphology and performance of organic photovoltaic devices. The structure of solvent-cast active layers is a result of phase separation in mixtures of donor and acceptor components. To a large extent, this process depends on the interactions between the components of the mixture. Here, we present a systematic analysis of the morphology of poly[N-9′-heptadecanyl-2,7-carbazole-alt-5,5-(4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)] (PCDTBT) and [6,6]-phenyl-C71-butyricacid methyl ester (PC70BM) films in terms of the ternary phase diagram. The interaction parameters between PCDTBT and four different solvents, namely chloroform, chlorobenzene, o-dichlorobenzene, and toluene, were estimated based on swelling experiments. Based on these values, ternary phase diagrams of PCDTBT:PC70BM in different solvents were calculated. The morphology of spin-coated films with different blend ratios cast from different solvents is discussed in terms of the obtained phase diagrams.

The recent technological developments in the field of single-cell RNA-Seq enable us to assay the transcriptome of up to a million single cells in parallel. However, the analyses of such big datasets present a major challenge. During the last decade, a wide variety of strategies have been proposed covering different steps of the analysis. Here, we introduce a selection of computational tools to provide an overview of a generic analysis pipeline.The first step of every scRNA-Seq experiment is proper study design, which does not require sophisticated experimental or informatics skills but is nonetheless presumably the most important step. The quality of the resulting data strictly depends on the proper planning of the experiment, including the selection of the most suitable technology for the biological question of interest as well as an elaborated study design to minimize the influence of confounding factors. Once the experiment has been conducted, the raw sequencing data needs to be processed to extract the gene expression information for each cell. This task comprises quality assessment of the sequenced reads, alignment against a reference genome, demultiplexing of the cell barcodes, and quantification of the reads/transcripts per gene. As any other transcriptomics technology, single-cell mRNA-Seq requires data normalization to assure sample-to-sample, here cell-to-cell, comparability and the consideration of confounding factors.Once gene expression values have been extracted from the reads and normalized, the researcher has the agony of choosing between a plethora of analysis approaches to investigate diverse aspects of the single-cell transcriptomes, such as dimensionality reduction and clustering to explore cellular heterogeneity or trajectory analysis to model differentiation processes.In this chapter, we present a wrap-up of the abovementioned steps to conduct single-cell RNA-Seq analyses and present a selection of existing tools.

Introduction: Elevated glucocorticoid (GC) activity, while difficult to accurately quantify, has been implicated in the pathophysiology of multiple cancer types. Approximately half of adrenocortical carcinoma (ACC) patients exhibit excess GC (GC+), which provides a unique test case to assess correlates of GC activity. The broad immunosuppressive effects of GC may limit tumor immune response and immune checkpoint inhibitor (ICI) efficacy. ACC multi-omics were analyzed to identify the molecular consequences of GC activity and assess the rationale for combining relacorilant, a glucocorticoid receptor (GR) antagonist, with an ICI in GC+ ACC. Methods: GC status, mRNA expression, DNA mutation, and DNA methylation data from distinct adrenal resections (n=71) were accessed via The Cancer Genome Atlas (TCGA). To deconvolute immune cell type abundance, xCell was applied to the mRNA data. Random forest was used to derive gene signatures. Results: The expression of 858 genes differed significantly between GC- and GC+ ACC cases. KEGG pathway analysis showed higher gene expression of 7 pathways involved in steroid synthesis and secretion in GC+ cases. Nineteen pathways showed lower expression, most of which were related to natural killer cells, T-cells, and immune activity. Hypomethylation was primarily observed in the steroid synthesis pathways. Tumor-infiltrating CD4+ memory (P=.003), CD8+ memory (P Conclusions: Reduced abundance of immune cells and immune-related transcripts in GC+ ACC provides insight into the mechanisms by which GC may limit response to ICI therapy. GR antagonism may increase immune related transcripts, thus promoting tumor immune response in GC+ ACC and other malignancies with elevated GC activity. This hypothesis will be tested in a Phase 1 trial of relacorilant + ICI. Citation Format: Andrew E. Greenstein, Mouhammed Amir Habra, Marzena Mura, Paweł Biernat, Marek J. Piatek, Andreas Grauer, Stacie Peacock Shepherd. Suppression of tumor immune activity in adrenocortical carcinoma with excess glucocorticoid [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-130.

Highlights • Higher mortality rate in COVID-19 patients with haematologic diseases. • Haematologic patients with COVID-19 have 50 % less chance of survival. • Probability of death was higher in patients older than 40 yrs of age with AML/MDS., Background Here we report nosocomial outbreak of COVID-19 among patients in a haematological unit. To our knowledge this is the first report from Central Europe comparing morbidity and mortality in infected and non-infected patients after exposure to SARS-CoV-2. Methods The outbreak involved 39 individuals: 19 patients and 20 health care workers. The SARS-CoV-2 test by nasopharyngeal swabs was performed by real-time RT-PCR. Exposed patients were divided into two groups: quarantine patients with and without COVID-19. All patients were prospectively examined at the following time points: 0, 7 days, 14 days, 21 days and 28 days after confirmation or exclusion of SARS-CoV-2. Results Infection was confirmed in a total of 5/20 health care workers and 10/19 patients. Among the patients positive for SARS-CoV-2 infection, the mortality rate was 36.8 %. The probability of death in patients infected with SARS-CoV-2 increased 8-fold (p = 0.03). Bacterial, fungal, and viral co-infection significantly decreased survival in these patients (p

Next generation sequencing (NGS) is the driving force behind precision medicine and is revolutionizing most, if not all, areas of the life sciences. Particularly when targeting the major common diseases, an exponential growth of NGS data is foreseen for the next decades. This enormous increase of NGS data and the need to process the data quickly for real-world applications requires to rethink our current compute infrastructures. Here we provide evidence that memory-driven computing (MDC), a novel memory-centric hardware architecture, is an attractive alternative to current processor-centric compute infrastructures. To illustrate how MDC can change NGS data handling, we used RNA-seq assembly and pseudoalignment followed by quantification as two first examples. Adapting transcriptome assembly pipelines for MDC reduced compute time by 5.9-fold for the first step (SAMtools). Even more impressive, pseudoalignment by near-optimal probabilistic RNA-seq quantification (kallisto) was accelerated by more than two orders of magnitude with identical accuracy and indicated 66% reduced energy consumption. One billion RNA-seq reads were processed in just 92 seconds. Clearly, MDC simultaneously reduces data processing time and energy consumption. Together with the MDC-inherent solutions for local data privacy, a new compute model can be projected pushing large scale NGS data processing and primary data analytics closer to the edge by directly combining high-end sequencers with local MDC, thereby also reducing movement of large raw data to central cloud storage. We further envision that other data-rich areas will similarly benefit from this new memory-centric compute architecture.

The recent technological developments in the field of single-cell RNA-Seq enable us to assay the transcriptome of up to a million single cells in parallel. However, the analyses of such big datasets present a major challenge. During the last decade, a wide variety of strategies have been proposed covering different steps of the analysis. Here, we introduce a selection of computational tools to provide an overview of a generic analysis pipeline.The first step of every scRNA-Seq experiment is proper study design, which does not require sophisticated experimental or informatics skills but is nonetheless presumably the most important step. The quality of the resulting data strictly depends on the proper planning of the experiment, including the selection of the most suitable technology for the biological question of interest as well as an elaborated study design to minimize the influence of confounding factors. Once the experiment has been conducted, the raw sequencing data needs to be processed to extract the gene expression information for each cell. This task comprises quality assessment of the sequenced reads, alignment against a reference genome, demultiplexing of the cell barcodes, and quantification of the reads/transcripts per gene. As any other transcriptomics technology, single-cell mRNA-Seq requires data normalization to assure sample-to-sample, here cell-to-cell, comparability and the consideration of confounding factors.Once gene expression values have been extracted from the reads and normalized, the researcher has the agony of choosing between a plethora of analysis approaches to investigate diverse aspects of the single-cell transcriptomes, such as dimensionality reduction and clustering to explore cellular heterogeneity or trajectory analysis to model differentiation processes.In this chapter, we present a wrap-up of the abovementioned steps to conduct single-cell RNA-Seq analyses and present a selection of existing tools.

We report a multistep strategy of biochemical surface modifications that resulted in the synthesis of new, effective and biocompatible intravascular implants coating with immobilized anti-CD133 antibodies, that proved to be the most effective in endothelial progenitor cells capture and reduced smooth muscle cells growth. Biomolecules were immobilized on differently functionalized surfaces. The distribution, nanostructural characteristics and intramolecular interactions of anti-CD133 molecules as well as their ability to bind EPCs was evaluated. We also tempted to build a molecular model of the CD133 protein to study antigen-antibody interactions. CD133 protein is expressed in endothelial progenitor cells (EPCs). Absence of preferential interaction site on CD133, but rather a presence of a small binding area, may be the specificity of reconnaissance sequence, thus importantly increasing the probability of CD133 protein binding. After all, regarding our molecular model, we are convinced that specific, and large enough interactions between anti-CD133 coating stent surface and CD133 present on EPCs will reduce risk of restenosis by favoring the endothelial growth. Additionally, the safety study of the vivo performance of modified titania based surface was performed using small animal models. No allergological or toxical local or systemic adverse effects of the developed coatings were noted.

BACKGROUND: In an aging society, many patients require long-term treatment. This fact is associated clearly with the simultaneous occurrence of lifestyle diseases such as hypertension, diabetes, and even osteoarthritis. Concomitant medications, which are a common practice, pose a major threat of an interaction between these drugs. Very popular now "fast way of life" that makes people have less and less time to prepare well-balanced meals of high nutritional value. The result of this lifestyle is an increased need for supplementation preparations necessary vitamins and minerals. Given the wide availability of dietary supplements (shops, kiosks, petrol stations) raises the question about the possibility of an interaction between the uncontrolled intake of dietary supplements and medications received in the most common diseases of civilization. OBJECTIVES: The aim of this study was to investigate the effect of the most important minerals (magnesium, potassium, calcium, zinc) contained in the popular nutritional supplements, the release also often used as an anti-pain, anti-inflammatory, diclofenac sodium from the different formulations. RESULTS: Among the many as sodium diclofenac selected two most common: film-coated tablets and sustained release capsules. The study showed a significant effect of minerals on the release of diclofenac sodium and differences that impact, depending on the test form of the drug.

The harmonic map heat flow is a geometric flow well known to produce solutions whose gradient blows up in finite time. A popular model for investigating the blow-up is the heat flow for maps $\mathbb R^{d}\to S^{d}$, restricted to equivariant maps. This model displays a variety of possible blow-up mechanisms, examples include self-similar solutions for $3\le d\le 6$ and a so-called Type II blow-up in the critical dimension $d=2$. Here we present the first constructive example of Type II blow-up in higher dimensions: for each $d\ge7$ we construct a countable family of Type II solutions, each characterized by a different blow-up rate. We study the mechanism behind the formation of these singular solutions and we relate the blow-up to eigenvalues associated to linearization of the harmonic map heat flow around the equatorial map. Some of the solutions constructed by us were already observed numerically.

We consider the heat flow of corotational harmonic maps from $\mathbb R^3$ to the three-sphere and prove the nonlinear asymptotic stability of a particular self-similar shrinker that is not known in closed form. Our method provides a novel, systematic, robust, and constructive approach to the stability analysis of self-similar blowup in parabolic evolution equations. In particular, we completely avoid using delicate Lyapunov functionals, monotonicity formulas, indirect arguments, or fragile parabolic structure like the maximum principle. As a matter of fact, our approach reduces the nonlinear stability analysis of self-similar shrinkers to the spectral analysis of the associated self-adjoint linearized operators., Comment: 31 pages

We consider equivariant wave maps from the $(d+1)$--dimensional Minkowski spacetime into the $d$-sphere for $d\geq 4$. We find a new explicit stable self-similar solution and give numerical evidence that it plays the role of a universal attractor for generic blowup. An analogous result is obtained for the $SO(d)$ symmetric Yang-Mills field for $d\geq 6$., 9 pages, 2 figures

We analyze the finite-time blow-up of solutions of the heat flow for $k$-corotational maps $\mathbb R^d\to S^d$. For each dimension $d>2+k(2+2\sqrt{2})$ we construct a countable family of blow-up solutions via a method of matched asymptotics by glueing a re-scaled harmonic map to the singular self-similar solution: the equatorial map. We find that the blow-up rates of the constructed solutions are closely related to the eigenvalues of the self-similar solution. In the case of $1$-corotational maps our solutions are stable and represent the generic blow-up., 26 pages, 5 figures

Biodegradable carrier materials with nontoxic degradation products are very valuable for delivering drugs and biologically active molecules. Many organic systems (such as liposomes, micelles and polymeric nanoparticles) and inorganic systems (metal oxides and silica) have been researched for delivering active substances to organs. Silica seems to be one of the most interesting and promising materials.The aim of this study was to investigate the SiO2 elimination process from rats' organisms and to ascertain the distribution and prospective accumulation sites of the silica particles.A suspension of silica particles (Ø 150 nm) in 0.9% NaCl solution was introduced into rats' circulatory system. The degradation of these particles over time and their accumulation in the heart, lungs, kidneys and liver were observed.It was found that 36% of the introduced silica particles were excreted with urine after four days. The remaining particles were accumulated in the kidneys and lungs, probably in the lung air sacs and kidney glomerulus.Silica seems to be promising carrier material. Silica particles dissolve in the rat's body and are eliminated in urine.

Using mixed analytical and numerical methods we investigate the development of singularities in the heat flow for corotational harmonic maps from the $d$-dimensional sphere to itself for $3\leq d\leq 6$. By gluing together shrinking and expanding asymptotically self-similar solutions we construct global weak solutions which are smooth everywhere except for a sequence of times $T_1, Comment: 24 pages, 8 figures, minor corrections, matches published version