Reply to Sergent et al. Comment on "Balwierz et al. Potential Carcinogens in Makeup Cosmetics. Int. J. Environ. Res. Public Health 2023, 20, 4780".

Comments by Sergent et al. (2023) [...].

Association of bone mineral density and potential risk factors for osteoporosis in patients with severe haemophilia A.

INTRODUCTION: In people with haemophilia (PWH), recurrent episodes of bleeding lead to joint deterioration and bone resorption. To date, the effects of various other factors on bone mineral density (BMD) reduction have found conflicting results. AIM: The aim of this study was to analyse the relationships between BMD, bone mineral content (BMC), and trabecular bone score (TBS) parameters based on the dual X-ray absorptiometry method (DXA) and potential risk factors for osteoporosis in patients with severe haemophilia A. METHODS: Fifty-five men with severe haemophilia A, aged 18-68 years, and 59 healthy volunteer men were enrolled in this study. Densitometric-derived lumbar spine and femoral neck BMD, BMC, and TBS were measured. Blood analyses were performed for morphology parameters, liver and kidney function parameters, and viral status. Serum levels of oestradiol (E2 ), testosterone (T), dehydroepiandrosterone sulphate (DHEA-S), parathormone, and vitamin D were measured. RESULTS: Patients showed significantly lower BMD compared to controls (p < .003). The result below the expected range for age was nearly double (6.82% vs. 3.92%) in PWH under 50 years old compared to controls. Haemophilic patients also exhibited significantly higher vitamin D3 deficiency (p < .0001), which was strongly associated with low TBS. Additionally, low body mass index and high neutrophil/lymphocyte ratio were correlated with low BMC and BMD. CONCLUSIONS: This study confirms the prevalence of low BMD and BMC in patients with haemophilia in Poland. Factors that contribute to low BMD are primarily vitamin D deficiency, low BMI, high neutrophil/lymphocyte ratio, and low testosterone/oestradiol ratio.

Reply to Chaudhuri et al. Comment on "Balwierz et al. Potential Carcinogens in Makeup Cosmetics. Int. J. Environ. Res. Public Health 2023, 20, 4780".

Comments by Chaudhuri et al. (2023) [...].

Natural Ingredients of Transdermal Drug Delivery Systems as Permeation Enhancers of Active Substances through the Stratum Corneum.

In recent years, significant progress has been made in transdermal drug delivery systems, but there is still a search for enhancers that can improve the absorption of active substances through the stratum corneum. Although permeation enhancers have been described in the scientific literature, the use of naturally occurring substances in this role is still of particular interest, because they can offer a high level of safety of use, with a low risk of skin irritation, and high efficiency. In addition, these ingredients are biodegradable, easily available, and widely accepted by consumers due to the growing trust in natural compounds. This article provides information on the role of naturally derived compounds in transdermal drug delivery systems that help them penetrate the skin. The work focuses on the components found in the stratum corneum such as sterols, ceramides, oleic acid, and urea. Penetration enhancers found in nature, mainly in plants, such as terpenes, polysaccharides, and fatty acids have also been described. The mechanism of action of permeation enhancers in the stratum corneum is discussed, and information on the methods of assessing their penetration efficiency is provided. Our review mainly covers original papers from 2017 to 2022, supplemented with review papers, and then older publications used to supplement or verify the data. The use of natural penetration enhancers has been shown to increase the transport of active ingredients through the stratum corneum and can compete with synthetic counterparts.

Nanoparticles coated by chloramphenicol in hydrogels as a useful tool to increase the antibiotic release and antibacterial activity in dermal drug delivery.

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.

Potential Carcinogens in Makeup Cosmetics.

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.

Machine learning on the road to unlocking microbiota's potential for boosting immune checkpoint therapy.

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.

Nano-Silica Carriers Coated by Chloramphenicol: Synthesis, Characterization, and Grinding Trial as a Way to Improve the Release Profile.

Silica nanoparticles were applied as the carrier of chloramphenicol (2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide), and were loaded in a 1% carbopol-based gel (poly(acrylic acid)), which allowed obtainment of an upgraded drug form. The samples of silica materials were obtained by means of modified Stöber synthesis, and their morphological properties were analyzed using Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET) method, elemental analysis (EA), thermogravimetric analysis (TGA), analysis of the specific surface properties, X-ray diffraction study (XRD), scanning electron microscope (SEM), and dynamic light scattering (DLS) methods, which permitted the selection of the drug carrier. The two obtained silica carriers were coated with chloramphenicol and loaded into 1% carbopol gel. The release studies were then performed. The release results were evaluated using mathematical models as well as model-independent analysis. It was found that the modification of the synthesis of the silica by the sol-gel method to form a product coated with chloramphenicol and further grinding of the silica material influenced the release of the active substance, thus allowing the modification of its pharmaceutical availability. The change in the parameters of silica synthesis influenced the structure and morphological properties of the obtained silica carrier. The grinding process determined the way of adsorption of the active substance on its surface. The studies showed that the proper choice of silica carrier has a considerable effect on the release profile of the prepared hydrogel formulations.

Early Administration of Convalescent Plasma Improves Survival in Patients with Hematological Malignancies and COVID-19.

The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes. Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies. We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48-72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy. Overall survival in those who received convalescent plasma was significantly higher than in the historical group (p = 0.03460). The plasma-treated group also showed a significantly milder course of infection (p = 0.03807), characterized by less severe symptoms and faster recovery (p = 0.00001). In conclusion, we have demonstrated that convalescent plasma is an effective treatment and its early administration leads to clinical improvement, increased viral clearance and longer overall survival in patients with hematological malignancies and COVID-19. To our knowledge, this is the first report to analyze the efficacy of convalescent plasma in a cohort of patients with hematological malignancies.

Phenotypic and Genotypic Analysis of Resistant Helicobacter pylori Strains Isolated from Children with Gastrointestinal Diseases.

Antibiotic resistance of Helicobacter pylori is currently a global issue. The aim of this study was to analyze actual antibiotic resistance rates of H. pylori strains isolated from children with primary infections and to compare the incidence of mutations that determine resistance to clarithromycin (CH) and metronidazole (MET) in children with different clinical diagnoses. A total of 91 H. pylori strains were isolated from 108 children with primary infections. Drug susceptibility testing of the strains was performed using E-test method. Classical sequencing of DNA fragments was used to detect point mutations for CH and MET resistance. Resistance to CH was detected in 31% of isolated strains (28/91), while resistance to MET and CH was detected in 35% (32/91) of strains. A2143G was the most frequently detected mutation and was dominant among strains isolated from children with peptic ulcer disease (80%). Mutations in the rdxA gene were found significantly more frequently among MET-resistant strains than MET-sensitive strains (p = 0.03, Chi2 = 4.3909). In children, a higher frequency of H. pylori multiresistant strains was observed compared with the previous study in the same area. Differences were found in the occurrence of point mutations among H. pylori strains resistant to CH isolated from children with different clinical diagnoses.

Nosocomial outbreak of SARS-CoV-2 infection in a haematological unit - High mortality rate in infected patients with haematologic malignancies.

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 < 0.05). Additionally, the probability of death was much higher in patients older than 40 years of age (p = 0.032). CONCLUSION: This study showed significantly higher mortality rate in COVID-19 patients with haematologic diseases compared to the non-infected patient group. Haematologic patients with COVID-19 have 50 % less chance of survival.

A Bioinformatic Toolkit for Single-Cell mRNA Analysis.

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.

Functionalized CD133 antibody coated stent surface simultaneously promotes EPCs adhesion and inhibits smooth muscle cell proliferation-A novel approach to prevent in-stent restenosis.

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.

Occurrence of Demodex species in patients with blepharitis and in healthy individuals: a 10-year observational study.

PURPOSE: 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. STUDY DESIGN: 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. METHODS: 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. RESULTS: 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). CONCLUSION: The prevalence of ocular demodicosis is significantly correlated with blepharitis and increases with age.

The impact of selected preparations of trace elements - magnesium, potassium, calcium, and zinc on the release of diclofenac sodium from enteric coated tablets and from sustained release capsules.

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.

In vivo study on the biodistribution of silica particles in the bodies of rats.

BACKGROUND: 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. OBJECTIVES: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Silica seems to be promising carrier material. Silica particles dissolve in the rat's body and are eliminated in urine.