Search

The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV)mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIVmac251, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.

Introduction: Clinical experience, as well as the results of real-world data analysis point to the need for developing a model for the care of patients with drug-resistant depression, which could lead to improved access to effective and safe treatment. Scientific studies carried out to date have unequivocally documented the mode of action of ketamine and identified factors which can influence the efficacy of single infusions of ketamine for depression as well as in cases of affective bipolar disorder. Material and method: Case report including a review of national and international literature and an analysis of the case in the light Polish of EU law. Discussion: The use of ketamine in the treatment of drug-resistant depression raises question regarding its legal qualification, in particular whether such treatment can be characterized as a medical experiment. Conclusions: In the light of international publications, which confirm the validity of the method described above, one might assume that the treatment could be qualified as off-label use of a medicine, but not as a medical experiment as it is understood in the legislation (art. 21 ZawLekU). However, given the nature of this treatment, its qualification as off-label use is not the only one possible and others cannot be immediately ruled out.

The text, based on the author’s own research, describes the case of a student with a hearing impairment in the context of the effects of the COVID-19 pandemic. The main aim of the research was to answer the question: how did a person with a hearing impairment function during the pandemic and in what dimensions is the pandemic situation a crisis for the examined student with a hearing impairment? The article begins with an introduction to the discussed issues, then takes into account a short description of the studied student and the results of the analysis of the research material obtained with the use of a free-form interview. The article ends with conclusions and a summary. It should be emphasized that the described case can only be treated as a pilot study and preparation of the ground for further explorations of a wider scope.

In order to ensure the highest level of maritime travel safety, standards and rules are applied aimed at eliminating potential risks. In view of changes in the environment – as a result of, among others, the Covid-19 pandemic and Russia’s aggression against Ukraine – it has become necessary to verify expec-tations and preferences towards the provision of maritime transport services from the perspective of its users, representing generation Y. A key factor for evaluating cruise maritime service in the situation of current threats was identi-fied to achieve the objective of this study. At the same time, groups of factors responsible for the emergence of threats to travelers were identified, and pro-posals for measures to increase confidence in maritime transportation were evaluated from the perspective of the surveyed participants.

Reprezentanci pokolenia Y podejmują decyzje konsumenckie w rzeczywistości VUCA. Wykazują silne preferencje w zakresie przygotowania i organizacji podróży, dla których wzory realizacji oparte zostały o własne poczucie bezpieczeństwa. Skutki trwającej pandemii Covid-19 oraz wojny w Ukrainie stały się impulsem dla weryfikacji oczekiwań i preferencji osób urodzonych w latach 1982-2002 w zakresie świadczenia handlowej usługi lotniczej. Na podstawie opinii respondentów przynależących do pokolenia Y, potwierdzono redefinicję bezpieczeństwa wybranych środków transportu wobec otaczającej rzeczywistości i zidentyfikowano zależność pomiędzy oceną jakości pasażerskiego transportu lotniczego a poczuciem bezpieczeństwa.

The aim of the study was to investigate the distribution of elements (Ca, Mg, Fe, P, Zn, Na, K, Cu, Cr, Mo, Co, Se) analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES) and fluorides (F

Sleep is a very important aspect of human life, as it is responsible for regulation of the circadian cycle, body regeneration and reduction of harmful metabolites. Sleep deprivation can be associated with chronic stress, which can have an extremely negative impact on bodily function. The presented study covered 220 students of medical faculties; their correlations between the sleep quality and the level of perceived stress were analyzed. Sleep quality was measured using the PSQI (Pittsburgh Sleep Quality Index), and perceived stress was measured using PSS-10 (10-Item Perceived Stress Scale). A high correlation was shown between the PSQI and PSS-10 results (rs = 0.60), which means that people who were characterized by a low sleep quality also showed a high level of perceived stress. Among the PSQI components that were the most correlated with PSS-10, can be counted in such components as C1 (subjective sleep quality, rs = 0.50), C2 (sleep latency, rs = 0.51), and C7 (daytime dysfunctions, rs = 0.52). Mobile phone usage at bedtime has also been demonstrated to correlate with poor sleep quality. The study shows a significant relationship between sleep quality and the level of perceived stress, which has also been shown in other studies.

Studies suggest that the protection against SIV/simian-human immunodeficiency virus (SHIV) acquisition afforded by the SIV/HIV V1 deletion-containing envelope immunogens, delivered by the DNA/ALVAC vaccine platform, requires multiple innate and adaptive host responses. Anti-inflammatory macrophages and tolerogenic dendritic cells (DC-10), together with CD14 + efferocytes, are consistently found to correlate with a vaccine-induced decrease in the risk of SIV/SHIV acquisition.

The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to vaccination. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Central to vaccine efficacy is the engagement of the CCL2/CCR2 axis and tolerogenic dendritic cells producing IL-10 (DC-10). Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway and increased systemic levels of miRNA-139-5p, a negative regulator of expression of the cAMP-specific phosphodiesterase PDE4D, correlated with vaccine efficacy. These data posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

Among the Next-Generation Nuclear Plant (NGNP) designs, the High-Temperature Gas-Cooled Reactors (HTGRs) are very attractive, due to their inherent safety features, high power conversion efficiency, and potential of providing high-temperature process heat. To perform a thorough safety study and to license these types of reactors, sufficient information needs to be provided about the phenomena that occur during accident scenarios. While several experimental research efforts have been dedicated in the past to investigate accident scenarios, knowledge gaps still exist in the phenomena characteristic of pressurized and depressurized conduction cooldown (PCC/DCC) transients as well as for normal operation scenarios. This paper summarizes the Oregon State University High Temperature Test Facility (HTTF) test matrix, experimental campaign, and selected tests results. High Temperature Test Facility is a scaled Integral Test Facility (IET) that is capable of mimicking scaled dimensions and operational conditions of the Modular High-Temperature Gas Cooled Reactor (MHTGR). The goal of the High Temperature Test Facility is to provide experimental data on the DCC, PCC and normal operating scenarios of the reference Modular High-Temperature Gas Cooled Reactor design. The DCC, PCC, mixing, heat up and cooldown tests described in this paper were performed at prototypical Modular High-Temperature Gas Cooled Reactor temperatures, scaled initial pressure conditions (∼200 kPa), and thermal power input of less than 70 kW. Presented test data show temperature distributions in the High Temperature Test Facility core, upper plenum, cross duct, or lower plenum. Based on these temperature profiles attempts to investigate stratified flow, natural convection flow, heat up, cooldown and mixing phenomena are made. Furthermore, this paper evaluates the performed test campaign in the light of the Very High Temperature Gas-cooled Reactor Phenomena Identification and Ranking Table (PIRT) and proposes experiments to complement the existing PCC/DCC testing database for the validation of the thermal-hydraulic codes.

Unsupervised anomaly detection (AD) is critical for a wide range of practical applications, from network security to health and medical tools. Due to the diversity of problems, no single algorithm has been found to be superior for all AD tasks. Choosing an algorithm, otherwise known as the Algorithm Selection Problem (ASP), has been extensively examined in supervised classification problems, through the use of meta-learning and AutoML, however, it has received little attention in unsupervised AD tasks. This research proposes a new meta-learning approach that identifies an appropriate unsupervised AD algorithm given a set of meta-features generated from the unlabelled input dataset. The performance of the proposed meta-learner is superior to the current state of the art solution. In addition, a mixed model statistical analysis has been conducted to examine the impact of the meta-learner components: the meta-model, meta-features, and the base set of AD algorithms, on the overall performance of the meta-learner. The analysis was conducted using more than 10,000 datasets, which is significantly larger than previous studies. Results indicate that a relatively small number of meta-features can be used to identify an appropriate AD algorithm, but the choice of a meta-model in the meta-learner has a considerable impact., Comment: 16 pages, 4 figures

The promoting effect of FLG loss-of-function mutations on the development of atopic dermatitis (AD) signifies the role of filaggrin in the formation of a protective skin barrier; FLG mutations are also linked to asthma, food allergy and allergic rhinitis despite the absence of the protein in the affected tissues (lungs, intestines, and the majority of the nasal mucosa). AD patients suffer from chronic inflammation and recurrent skin infections; inflammation often precedes the appearance of spatially distant allergic manifestations. Here we show that exosome-enriched small extracellular vesicles (sEVs) secreted by filaggrin-knockdown keratinocytes are extensively remodelled as a consequence of the abnormal keratinocyte differentiation process. This alteration modulates the sEV capacity to promote type 1 and type 2 CD1a-dependent T cell responses by direct effects on self-lipid neoantigen generation; both modulating the amount of permissive (stimulatory) and non-permissive (inhibitory) CD1a ligands released from the sEV membranes by phospholipase A2. We found that this aberrant sEV lipid composition reflects a generalised cellular lipid bias with downregulation of multiple enzymes of lipid metabolic pathways, observed both in filaggrin knockdown keratinocytes in vitro, and in the skin of AD patients. Provision of modulatory ligands by sEVs secreted on a filaggrin insufficiency background, impeding both homeostatic autoreactive and protective antimicrobial CD1a-mediated type 1 and enhancing type 2 T cell responses provides basis for reduced tissue integrity and pathogen clearance and perpetuates inflammation in AD skin as well as in distant tissues to which sEVs are transferred by systemic circulation.

Background: Evaluating the tumor response to neoadjuvant chemotherapy is key to planning further therapy of breast cancer. Our study aimed to evaluate the effectiveness of low-energy and subtraction contrast-enhanced spectral mammography (CESM) images in the detection of complete response (CR) for neoadjuvant chemotherapy (NAC) in breast cancer. Methods: A total of 63 female patients were qualified for our retrospective analysis. Low-energy and subtraction CESM images just before the beginning of NAC and as a follow-up examination 2 weeks before the end of chemotherapy were compared with one another and assessed for compliance with the postoperative histopathological examination (HP). The response to preoperative chemotherapy was evaluated based on the RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Results: Low-energy images tend to overestimate residual lesions (6.28 mm) and subtraction images tend to underestimate them (2.75 mm). The sensitivity of low-energy images in forecasting CR amounted to 33.33%, while the specificity was 92.86%. In the case of subtraction CESM, the sensitivity amounted to 85.71% and the specificity to 71.42%. Conclusions: CESM is characterized by high sensitivity in the assessment of CR after NAC. The use of only morphological assessment is insufficient. CESM correlates well with the size of residual lesions on histopathological examination but tends to underestimate the dimensions.

Filaggrin (FLG) protein is indispensable for multiple aspects of the epidermal barrier function but its accumulation in a monomeric filaggrin form may initiate premature keratinocytes death; it is unclear how filaggrin levels are controlled before the formation of storing keratohyalin granules. Here we show that keratinocyte-secreted small extracellular vesicles (sEVs) may contain filaggrin-related cargo providing a route of eliminating excess filaggrin from keratinocytes. Filaggrin-containing sEVs are found in plasma in both healthy individuals and atopic dermatitis patients. Staphylococcus aureus (S. aureus) enhances packaging and secretion of filaggrin-relevant products within the sEVs for enhanced export via a TLR2-mediated mechanism which is also linked to the ubiquitination process. This filaggrin removal system, preventing premature keratinocyte death and epidermal barrier dysfunction, is exploited by S. aureus which promotes filaggrin elimination from the skin that could help safeguard bacterial growth.

Superconducting properties of two bismuthide intermetallic compounds, RbBi2 and CsBi2, were studied by means of experimental measurements and ab initio calculations. We show that in both compounds the superconductivity emerges from the pyrochlore Bi lattice and its formation is heavily influenced by relativistic effects. Based on our analysis of the effect of spin-orbit coupling on the electron-phonon coupling we suggest a possible criterion for finding new superconducting materials by looking for structures featuring relativistically-stabilized hypervalent networks of heavy p-block elements.

Burns exceeding 30% of total body surface area (TBSA) result in considerable hypovolemia coupled with the formation and release of inflammatory mediators, leading to subsequent systemic effects known as burn shock. Because of plasma exudation and the associated losses of large quantities of minerals, severe burns can lead to nutritional deficiencies and consequently disrupt homeostasis and metabolism of the entire body. The study group comprised 62 patients, who were divided into 3 groups according to the severity of burns. Serum samples were tested for concentrations of Ca, Mg, Mn, P, K, Zn, Cu, Fe, Se, Na, Cr, Ni, and Al. The mineral concentrations in serum of patients with burn injuries differ significantly from reference values, but this is not affected by the extent of the body burn. There are statistically significant decreases in serum concentrations of elements important for antioxidant protection (Zn, Cu, Se), and significant increases in the concentrations of toxic elements (Al and Ni), which may aggravate the effects associated with the state of burn shock. The Spearman rank correlation analysis did not reveal any statistically significant relationships between the serum concentrations of Mn, Ni, Al, K, Na, P, Mg, Zn, Se, Cr and the affected body surface area and severity of the burn—the values were at the lower end of the reference range. The obtained results indicate that proper nutrition, including elements replenishment, is extremely important in the recovery process of burn patients and time to nutrition is an important factor affecting patient survival after severe burn.

Background: Treatment with glucocorticoids (GCs) is associated with side effects. In contrast to the well-known negative impact on bone tissue exerted by oral GCs, few data are available regarding intravenous GCs. We investigated the influence of intravenous methylprednisolone (IVMP) on bone turnover markers (BTM): amino-terminal propeptide of type I procollagen (P1NP) and the C-terminal telopeptide of type I collagen (CTX), and on calcium metabolism parameters: 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), calcium (Ca), phosphate (P), and intact parathormone (iPTH). Methods: In a prospective study, 23 consecutive subjects with Graves’ orbitopathy were included and treated with IVMP according to the European Group on Graves’ Orbitopathy recommendations. We evaluated effects on BTM occurring during the first 7 days after 0.5 g IVMP, and after the therapy with 12 IVMP pulses with a cumulative dose of 4.5 g. Results: We observed prompt but transient decrease of P1NP (p < 0.001) and the reduction of CTX (p = 0.02) after the first IVMP pulse. Following the full course of IVMP therapy, both P1NP and CTX were found decreased (p < 0.05 and p < 0.01, respectively). Conclusions: A single pulse of 0.5 g IVMP already decreases bone formation and resorption; however, this change is transient. The full therapy is associated with suppression of bone turnover.

Candida albicans (C. albicans) infection is a potential complication in the individuals with atopic dermatitis (AD) and can affect clinical course of the disease. Here, using primary keratinocytes we determined that atopic milieu promotes changes in the interaction of small extracellular vesicles (sEVs) with dendritic cells and that this is further enhanced by the presence of C. albicans. sEV uptake is largely dependent on the expression of glycans on their surface; modelling of the protein interactions indicated that recognition of this pathogen through C. albicans-relevant pattern recognition receptors (PRRs) is linked to several glycosylation enzymes which may in turn affect the expression of sEV glycans. Here, significant changes in the surface glycosylation pattern, as determined by lectin array, could be observed in sEVs upon a combined exposure of keratinocytes to AD cytokines and C. albicans. This included enhanced expression of multiple types of glycans, for which several dendritic cell receptors could be proposed as binding partners. Blocking experiments showed predominant involvement of the inhibitory Siglec-7 and -9 receptors in the sEV-cell interaction and the engagement of sialic acid-containing carbohydrate moieties on the surface of sEVs. This pointed on ST6 β-Galactoside α-2,6-Sialyltransferase 1 (ST6GAL1) and Core 1 β,3-Galactosyltransferase 1 (C1GALT1) as potential enzymes involved in the process of remodelling of the sEV surface glycans upon C. albicans exposure. Our results suggest that, in combination with atopic dermatitis milieu, C. albicans promotes alterations in the glycosylation pattern of keratinocyte-derived sEVs to interact with inhibitory Siglecs on antigen presenting cells. Hence, a strategy aiming at this pathway to enhance antifungal responses and restrict pathogen spread could offer novel therapeutic options for skin candidiasis in AD.

W tekście opisano, na podstawie badań własnych, przypadek 65-letniej kobiety z zespołem Aspergera. Głównym celem badań było uzyskanie odpowiedzi na pytanie: jaka jest starość badanej kobiety z zespołem Aspergera? Artykuł rozpoczyna się od wprowadzenia teoretycznego w poruszaną problematykę, gdzie przedstawiono najważniejsze zagadnienia dotyczące zespołu Aspergera oraz starości i starzenia się z zaakcentowaniem teorii ciągłości. Następnie uwzględniono charakterystykę badanej kobiety w kontekście jej sytuacji rodzinnej, bytowej, edukacyjno-zawodowej, zdrowotnej, relacji międzyludzkich. Artykuł kończą wnioski i podsumowanie. Należy przy tym podkreślić, że opisany przypadek, może być traktowany jedynie jako badanie pilotażowe i przygotowanie gruntu dla kolejnych eksploracji o szerszym zakresie.

Motivation Viruses are the most abundant biological entities and constitute a large reservoir of genetic diversity. In recent years, knowledge about them has increased significantly as a result of dynamic development in life sciences and rapid technological progress. This knowledge is scattered across various data repositories, making a comprehensive analysis of viral data difficult. Results In response to the need for gathering a comprehensive knowledge of viruses and viral sequences, we developed Virxicon, a lexicon of all experimentally acquired sequences for RNA and DNA viruses. The ability to quickly obtain data for entire viral groups, searching sequences by levels of taxonomic hierarchy—according to the Baltimore classification and ICTV taxonomy—and tracking the distribution of viral data and its growth over time are unique features of our database compared to the other tools. Availabilityand implementation Virxicon is a publicly available resource, updated weekly. It has an intuitive web interface and can be freely accessed at http://virxicon.cs.put.poznan.pl/.

In this study, we investigated the ability of THP-1 monocytes and macrophages to accumulate lead (Pb) in vitro, relative to Pb concentration and length of exposure. Moreover, we also evaluated the effect of Pb accumulation on cell viability and apoptosis. THP-1 monocytes and macrophages were cultured in the presence of Pb at 1.25 μg/dL, 2.5 μg/dL, 5 μg/dL, and 10 μg/dL. Pb accumulation was examined by inductively coupled plasma and confocal microscopy. The influence of Pb on cell viability, apoptosis, and necrosis was assessed using flow cytometry. The results showed that Pb was toxic to THP-1 monocytes/macrophages even at very low environmental concentrations. Despite the use of low concentrations, both monocytes and macrophages showed dose-dependent and time-dependent decreases in viability, with a simultaneous increase in the percentage of early and late apoptotic cells. Macrophages reacted more strongly to Pb than monocytes. When exposed to the same Pb concentrations, they showed lower viability and a higher percentage of necrotic cells. The incubation time positively correlated with Pb accumulation in a dose-dependent manner. The obtained results indicate that environmental exposure to low Pb concentrations may significantly impair the function of macrophages, with the increased number of apoptotic cells potentially contributing to the development of many pathologies in the brain and whole body.

We present the crystallographic analysis, superconducting characterization and theoretical modeling of LiBi, that contains the lightest and the heaviest nonradioactive metal. The compound crystallizes in a tetragonal (CuAu-type) crystal structure with Bi square nets separated by Li planes (parameters a = 3.3636(1) Å and c = 4.2459(2) Å, c/a = 1.26). Superconducting state was studied in detail by magnetic susceptibility and heat capacity measurements. The results reveal that LiBi is a moderately coupled type-I superconductor (λe-p = 0.66) with Tc = 2.48 K and a thermodynamic critical field Hc(0) = 157 Oe. Theoretical studies show that bismuth square net is responsible for superconductivity in this compound, but the coupling between the Li planes and Bi planes makes a significant contribution to the superconductivity.

Honey is the most popular bee product consumed by humans. It is known for its nutritional properties and health benefits, which include neuroprotective effects, the support of the circulatory system, and the beneficial influence it has on skin and respiratory system disorders. The aim of this study was to determine the influence of water temperature used for the preparation of honey solutions on their antioxidant potential. Material and methods. The study material included buckwheat honey, black locust honey, and rape honey. Honey solutions (1%) were prepared using distilled water with the temperatures: 25°C, 70°C, 80°C, and 90°C. The antioxidant activity of samples was measured with spectrophotometric method using synthetic radical DPPH. The antioxidant activity of honey was between 0.29 to 78.50% of DPPH inhibition, depending on the type of honey and the temperature of water used for the preparation of solutions. Buckwheat honey was characterised by the highest antioxidant potential. A significant, directly proportional correlation was observed between the antioxidant potential and the temperature of buckwheat and rape II honey solutions. In the case of buckwheat honey, rape honey I and black locust honey, the highest antioxidant potential was achieved in solutions prepared using distilled water at 90°C, whereas in the case of rape honey II, the highest values were observed at 80°C and 90°C. The lowest inhibition of the DPPH radical was observed in solutions at 70°C in all of the honey types. In the case of the studied honeys, it is even advisable to prepare water solutions at 80°C or 90°C in order to increase its antioxidant potential, e.g. by adding honey to tea or milk.

Deficiency in a principal epidermal barrier protein, filaggrin (FLG), is associated with multiple allergic manifestations, including atopic dermatitis and contact allergy to nickel. Toxicity caused by dermal and respiratory exposures of the general population to nickel-containing objects and particles is a deleterious side effect of modern technologies. Its molecular mechanism may include the peptide bond hydrolysis in X1-S/T-c/p-H-c-X2 motifs by released Ni2+ ions. The goal of the study was to analyse the distribution of such cleavable motifs in the human proteome and examine FLG vulnerability of nickel hydrolysis. We performed a general bioinformatic study followed by biochemical and biological analysis of a single case, the FLG protein. FLG model peptides, the recombinant monomer domain human keratinocytes in vitro and human epidermis ex vivo were used. We also investigated if the products of filaggrin Ni2+-hydrolysis affect the activation profile of Langerhans cells. We found X1-S/T-c/p-H-c-X2 motifs in 40% of human proteins, with the highest abundance in those involved in the epidermal barrier function, including FLG. We confirmed the hydrolytic vulnerability and pH-dependent Ni2+-assisted cleavage of FLG-derived peptides and FLG monomer, using in vitro cell culture and ex-vivo epidermal sheets; the hydrolysis contributed to the pronounced reduction in FLG in all of the models studied. We also postulated that Ni-hydrolysis might dysregulate important immune responses. Ni2+-assisted cleavage of barrier proteins, including FLG, may contribute to clinical disease associated with nickel exposure.

Human T cell leukemia virus type 1 (HTLV-1) persists in the host despite a vigorous immune response that includes cytotoxic T cells (CTL) and natural killer (NK) cells, suggesting the virus has developed effective mechanisms to counteract host immune surveillance. We recently showed that in vitro treatment of HTLV-1-infected cells with the drug pomalidomide (Pom) increases surface expression of MHC-I, ICAM-1, and B7-2, and significantly increases the susceptibility of HTLV-1-infected cells to NK and CTL killing, which is dependent on viral orf-I expression. We reasoned that by restoring cell surface expression of these molecules, Pom treatment has the potential to reduce virus burden by rendering infected cells susceptible to NK and CTL killing. We used the rhesus macaque model to determine if Pom treatment of infected individuals activates the host immune system and allows recognition and clearance of HTLV-1-infected cells. We administered Pom (0.2 mg/kg) orally to four HTLV-1-infected macaques over a 24 day period and collected blood, urine, and bone marrow samples throughout the study. Pom treatment caused immune activation in all four animals and a marked increase in proliferating CD4+, CD8+, and NK cells as measured by Ki-67+ cells. Activation markers HLA-DR, CD11b, and CD69 also increased during treatment. While we detected an increased frequency of cells with a memory CD8+ phenotype, we also found an increased frequency of cells with a Treg-like phenotype. Concomitant with immune activation, the frequency of detection of viral DNA and the HTLV-1-specific humoral response increased as well. In 3 of 4 animals, Pom treatment resulted in increased antibodies to HTLV-1 antigens as measured by western blot and p24Gag ELISA. Consistent with Pom inducing immune and HTLV-1 activation, we measured elevated leukotrienes LTB4 and LTE4 in the urine of all animals. Despite an increase in plasma LTB4, no significant changes in plasma cytokine/chemokine levels were detected. In all cases, however, cellular populations, LTB4, and LTE4 decreased to baseline or lower levels 2 weeks after cessation of treatment. These results indicated that Pom treatment induces a transient HTLV-1-specific immune activation in infected individuals, but also suggest Pom may not be effective as a single-agent therapeutic.

A knitted implant, unilaterally modified with plasma-assisted chemical-vapor deposition (PACVD), and with a nano-layer of fluorine derivative supplementation, for reducing the risk of complications related to adhesions, and the formation of a thick postoperative scar was prepared. The biological evaluation of designed or modified medical devices is the main aspect of preclinical research. If such studies use a medical device with prolonged contact with connective tissue (more than 30 days), biocompatibility studies require a safety assessment in terms of toxicity in vitro and in vivo, allergenicity, irritation, and cancerogenicity, reproductive and developmental toxicity. The ultimate aspect of biological evaluation is biofunctionality, and evaluation of the local tissue response after implantation, resulting in the determination of all aspects of local biocompatibility with the implemented synthetic material. The implantation of PACVD-modified materials in muscle allows us to estimate the local irritation effect on the connective tissue, determining the risk of scar formation, whereas implantation of the above-mentioned knitted fabric into the abdominal wall, assists with evaluating the risk of fistula formation—the main post-surgical complications. The research aimed to evaluate the local reaction of the soft tissues after the implantation of the knitted implants modified with PACVD of the fluoropolymer in the nanostuctural form. The local effect that occurred during the implantation of the designed implants was quantitatively and qualitatively evaluated when PACVD unmodified (reference), and modified medical devices were implanted in the abdominal cavity (intra-abdominal position) for 12 or into the muscles for 56 weeks. The comparative semi-quantitative histological assessment included the severity of inflammatory cells (multinucleated cells, lymphocytes, plasma cells, macrophages, giant cells) and the tissue response (necrosis, neovascularization, fibrosis, and fat infiltration) on a five-point scale. The knitted implants modified by PACVD did not indicate cumulative tissue response when they were implanted in the muscle and intra-abdominally with direct contact with the viscera. They reduced local tissue reaction (score −2.71 after 56 weeks of the implantation) and internal organ adhesion (irritation score −2.01 and adhesion susceptibility −0.3 after 12 weeks of the implantation) compared with the reference (unmodified by PACVD) knitted implant, which had an identical structure and was made of the same source.

One area of glioblastoma research is the metabolism of tumor cells and detecting differences between tumor and healthy brain tissue metabolism. Here, we review differences in fatty acid metabolism, with a particular focus on the biosynthesis of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) by fatty acid synthase (FASN), elongases, and desaturases. We also describe the significance of individual fatty acids in glioblastoma tumorigenesis, as well as the importance of glycerophospholipid and triacylglycerol synthesis in this process. Specifically, we show the significance and function of various isoforms of glycerol-3-phosphate acyltransferases (GPAT), 1-acylglycerol-3-phosphate O-acyltransferases (AGPAT), lipins, as well as enzymes involved in the synthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and cardiolipin (CL). This review also highlights the involvement of diacylglycerol O-acyltransferase (DGAT) in triacylglycerol biosynthesis. Due to significant gaps in knowledge, the GEPIA database was utilized to demonstrate the significance of individual enzymes in glioblastoma tumorigenesis. Finally, we also describe the significance of lipid droplets in glioblastoma and the impact of fatty acid synthesis, particularly docosahexaenoic acid (DHA), on cell membrane fluidity and signal transduction from the epidermal growth factor receptor (EGFR).

Burns and their treatment are a significant medical problem. The loss of the physical barrier function of the skin opens the door to microbial invasion and can lead to infection. The repair process of the damage caused by the burn is impaired due to the enhanced loss of fluids and minerals through the burn wound, the onset of hypermetabolism with the concomitant disruption of nutrient supply, and derangements in the endocrine system. In addition, the initiated inflammatory and free radical processes drive the progression of oxidative stress, the inhibition of which largely depends on an adequate supply of antioxidants and minerals. Clinical experience and research provide more and more data to make the treatment of patients with thermal injury increasingly effective. The publication discusses disorders occurring in patients after thermal injury and the methods used at various stages of treatment.

Background: Intravenous glucocorticoids pulses administration is the main therapeutic option in the treatment of Graves’ orbitopathy. Such therapy could relate to the multiple adverse effects. The aim of the study is evaluation the influence of intravenous methylprednisolone (IVMP) pulse therapy on the heart rhythm (HR) changes in patients with active, moderate-to-severe Graves’ Orbitopathy (GO). Methods: We studied 20 patients with moderate-to-severe GO. All patients received 12 IVMP pulses (6x500 mg plus 6x250mg) at equal time intervals in a weekly schedule. We performed Holter ECG monitoring for 3 consecutive days (the day before, the day of IVMP and day after IVMP) to monitor HR and arrhythmias. We compared changes in HR between these 3 days and set time interval when the alteration was significant. This evaluation was performed during the 1st, 6th and 12th IVMP pulse. Results: Increased HR, in comparison with the day before, was registered on the day of IVMP administration. The most significant increase in HR started 5 hours (h) after a pulse administration and lasted 12 h. There were no significant differences in HR between the day before and the day after IVMP. We did not notice any major adverse cardiac events including severe arrhythmias. Conclusions: IVMP therapy is associated with increased HR, that occurs a few hours after infusion, lasts several hours and is transient. Keywords: Graves’ ophthalmopathy; Graves’ disease; glucocorticoids; heart rate

Intracellular processes are cascades of biochemical reactions, triggered in response to various types of stimuli. Mathematical models describing their dynamics have become increasingly popular in recent years, as tools supporting experimental work in analysis of pathways and regulatory networks. Not only do they provide insights into general properties of these systems, but also help in specific tasks, such as search for drug molecular targets or treatment protocols. Different tools and methods are used to model complex biological systems. In this work, we focus on ordinary differential equations (ODEs) and Petri nets. We consider specific methods of analysis of such models, i.e., sensitivity analysis (SA) and significance analysis. So far, they have been applied separately, with different goals. In this paper, we show that they can complement each other, combining the sensitivity of ODE models and the significance analysis of Petri nets. The former is used to find parameters, whose change results in the greatest quantitative and qualitative changes in the model response, while the latter is a structural analysis and allows indicating the most important subprocesses in terms of information flow in Petri net. Ultimately, both methods facilitate finding the essential processes in a given signaling pathway or regulatory network and may be used to support medical therapy development. In the paper, the use of dual modeling is illustrated with an example of ATM/p53/NF-$$\kappa$$ κ B pathway. Each method was applied to analyze this system, resulting in finding different subsets of important processes that might be prospective targets for changing this system behavior. While some of the processes were indicated in each of the approaches, others were found by one method only and would be missed if only that method was applied. This leads to the conclusion about the complementarity of the methods under investigation. The dual modeling approach of comprehensive structural and parametric analysis yields results that would not be possible if these two modeling approaches were applied separately. The combined approach, proposed in this paper, facilitates finding not only key processes, with which significant parameters are associated, but also significant modules, corresponding to subsystems of regulatory networks. The results provide broader insight into therapy targets in diseases in which the natural control of intracellular processes is disturbed, leading to the development of more effective therapies in medicine.

El presente trabajo trata sobre la inclusión laboral de las personas con sordoceguera. Como parte de la investigación se han realizado entrevistas a personas de este colectivo. Se ha indagado en cuestiones relacionadas con la integración con los compañeros de trabajo, las adaptaciones, las posibilidades en el mercado de trabajo y el papel que juega en la inclusión en el mundo laboral el empresario y el entorno laboral. Se ha podido concluir que es necesaria una importante labor de concienciación a nivel social en general y a nivel de las empresas en particular ya que no son conocidas ni las necesidades ni las capacidades de las personas sordociegas., Grado en Relaciones Laborales y Recursos Humanos

Objectives: The growing incidence of multidrug-resistant (MDR) bacteria is an inexorable and fatal challenge in modern medicine. Colistin is a cationic polypeptide considered a “last-resort” antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens. Plasmid-borne mcr colistin resistance emerged recently, and could potentially lead to essentially untreatable infections, particularly in hospital and veterinary (livestock farming) settings. In this study, we sought to establish the molecular basis of colistin-resistance in six extraintestinal Escherichia coli strains.Methods: Molecular investigation of colistin-resistance was performed in six extraintestinal E. coli strains isolated from patients hospitalized in Medical University Hospital, Bialystok, Poland. Complete structures of bacterial chromosomes and plasmids were recovered with use of both short- and long-read sequencing technologies and Unicycler hybrid assembly. Moreover, an electrotransformation assay was performed in order to confirm IncX4 plasmid influence on colistin-resistance phenotype in clinical E. coli strains.Results: Here we report on the emergence of six mcr-1.1-producing extraintestinal E. coli isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, mcr-1.1, has been proved to be encoded within a type IV secretion system (T4SS)-containing 33.3 kbp IncX4 plasmid pMUB-MCR, next to the PAP2-like membrane-associated lipid phosphatase gene.Conclusion: IncX4 mcr-containing plasmids are reported as increasingly disseminated among E. coli isolates, making it an “epidemic” plasmid, responsible for (i) dissemination of colistin-resistance determinants between different E. coli clones, and (ii) circulation between environmental, industrial, and clinical settings. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens.

The purpose of this review is to attempt to outline the potential role of fluoride in the pathogenesis of brain tumours, including glioblastoma (GBM). In this paper, we show for the first time that fluoride can potentially affect the generally accepted signalling pathways implicated in the formation and clinical course of GBM. Fluorine compounds easily cross the blood–brain barrier. Enhanced oxidative stress, disruption of multiple cellular pathways, and microglial activation are just a few examples of recent reports on the role of fluoride in the central nervous system (CNS). We sought to present the key mechanisms underlying the development and invasiveness of GBM, as well as evidence on the current state of knowledge about the pleiotropic, direct, or indirect involvement of fluoride in the regulation of these mechanisms in various tissues, including neural and tumour tissue. The effects of fluoride on the human body are still a matter of controversy. However, given the growing incidence of brain tumours, especially in children, and numerous reports on the effects of fluoride on the CNS, it is worth taking a closer look at these mechanisms in the context of brain tumours, including gliomas.

In the last two decades there can be observed a rapid development of systems biology. The basis of systems methods is a formal model of an analyzed system. It can be created in a language of some branch of mathematics and recently Petri net-based biological models seem to be especially promising since they have a great expressive power. One of the methods of analysis of such models is based on transition invariants. They correspond to some subprocesses which do not change a state of the modeled biological system. During such analysis, a need arose to study the subsets of transitions, what leads to interesting combinatorial problems - which have been considered in theory and practice.Two problems of anti-occurrence were considered. These problems concern a set of transitions which is not a subset of any of t-invariant supports or is not a subset of t-invariant supports from some collection of such supports. They are defined in a formal way, their computational complexity is analyzed and an exact algorithm is provided for one of them.A comprehensive analysis of complex biological phenomena is challenging. Finding elementary processes that do not affect subprocesses belonging to the entire studied biological system may be necessary for a complete understanding of such a model and it is possible thanks to the proposed algorithm.

Waste valorisation via biological production of widely used in the industry medium chain carboxylates (MCCs) via open culture fermentation (OCF) could be a promising alternative to the commonly used anaerobic digestion. Lactate-rich waste streams are considered as valuable substrates for carboxylate chain elongation (CE), however, there are certain limitations related to the production efficiency. Acetate produced and accumulated in the acetogenesis plays an important role in CE, i.e. acetate is elongated to butyrate and then to caproate which is most popular MCC. Henceforth, it was investigated whether the ratio of lactate to acetate (L:A) affected carboxylates yields and product distribution in the lactate-based CE in OCF. The tested L:A ratios influenced carboxylates selectivity in batch trials. In the ones with lactate as the sole carbon source, propionate production was predominant but when a higher relative acetate concentration was used, the production of butyrate and CE to caproate was favored. The co-utilization of lactate and acetate in a continuous process increased the production of butyrate and caproate compared to the phase with lactate as the sole carbon source, however, controlling the relative concentration of lactate and acetate during co-utilization was not an effective strategy for increasing caproate production. 16S rRNA gene amplicon reads mapping to Caproiciproducens were the most abundant in samples collected throughout the continuous processes regardless of the L:A ratios.

Allergic diseases are highly prevalent, and they can exert a significant influence on the patients’ physical and mental well-being, thus affecting the quality of their lives and society as a whole. The aim of this study was to evaluate parental knowledge about allergens, allergy symptoms, and treatment of allergies, and to identify problems with adherence to an elimination diet and the underlying difficulties. Twelve kindergartens and the parents of 1350 preschoolers took part in the first stage of the study. In a screening trial, allergies were diagnosed in 197 children, and their parents participated in the second stage of the study. The child’s age at the onset of the first symptoms was significantly correlated with allergy type. Age was significantly correlated with selected symptoms of an allergic reaction, and skin allergies were more prevalent in younger children. Erythema, skin reddening, and urticaria occurred more frequently in children aged 3–4 years (OR 1.45; 95%CI 1.24–1.77, p < 0.05) and were diagnosed in skin tests (OR 1.36; 95%CI 1.22–1.59, p < 0.05). Allergies to numerous food items were associated with a long-term elimination diet (OR 1.89; 95%CI 1.33–2.19, p < 0.01), as well as problems with preparing safe meals, shopping for food, or dietary adherence when eating out. According to the respondents, lack of support from other family members and compliance with dietary restrictions in kindergartens and when eating out posed the greatest barriers to dietary adherence. Parents do not have sufficient knowledge about environmental allergens and effective strategies for coping with acute allergic reactions, including anaphylactic shock. Children with diagnosed food allergies should enjoy a similar quality of life to their healthy peers, which is why the parents should be educated about diet therapy, duration of treatment, and safe food substitutes.

The aim of the publication is to present selected results of the research on distance education of students with disabilities in Polish higher education institutions during COVID-19 pandemics. The authors gathered the opinions from 291 students with various disabilities, and they performed the analysis of the implementation of online education process in pandemics from the perspective of this specific group. The publication includes the respondents’ experiences referring to different areas of distance education and to its positive and negative aspects. It also offers the assessment of online learning from the substantive and organisational angle and from the perspective of its influence on the psychic, physic and social sphere of the respondents’ functioning. Also the opinions of students with disabilities on the support they expected and the one they received and on their expectations for distance education to be better adjusted to their needs are included in the publication. Perspectives of students with different disability types and levels, representing various higher education institutions, different study programmes, cycles and stages of studying were taken into consideration in the research.