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Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with systemic inflammation and high impact on quality of life. Treatment strategies are still inadequate with a lack of inflammation biomarkers. We conducted a prospective study to assess the correlation between serum amyloid A (SAA) levels and active lesion count; disease severity; Dermatology Life Quality Index (DLQI); smoking; BMI; and lesion sites. Methods: Forty-one patients (M/F: 22/19) were enrolled. Demographic, clinical, laboratory, and therapeutic data were assessed at baseline on patients not under treatment or in wash-out from systemic treatment for at least 2 weeks. Associations were investigated by univariate and multivariate analyses. Results: SAA levels were significantly associated with number of nodules (p = 0.005), abscesses (p < 0.001), fistulas (p = 0.016), and severe IHS4 (p = 0.088 and r = 0.514). Gluteal localization was correlated with high values of mSartorius and severe IHS4. Conclusions: We recommend assessment of SAA levels to monitor therapeutic response in patient with HS in order to prevent disease’s flare and potential complications.

Enseñar idiomas extranjeros es un desafío para los profesores, pero para los adultos es aún más desafiante, ya que los adultos suelen tomar una decisión independiente e informada sobre el idioma extranjero específico que quieren aprender y tienen un alto nivel de motivación para lograrlo. Esto se debe a varios aspectos, pero la mayoría se debe a la necesidad oa las consecuencias de la vida laboral. Si bien el aprendizaje de lenguas extranjeras es obligatorio para los niños en edad escolar, los adultos lo hacen de forma voluntaria, lo que impone más exigencias a su enseñanza y métodos de enseñanza que a los jóvenes. Cada estudiante desarrolla su propio estilo de aprendizaje, a partir de las experiencias educativas previas adquiridas en niveles educativos anteriores, el contexto social y cultural de la familia en la que vivió, los modelos que ha adoptado de sus pares y su aplicación en las instituciones. El objetivo de este artículo es mostrar qué es la andragogía, cuáles son los aspectos técnicos del aprendizaje de adultos, así como la motivación para el aprendizaje de adultos y el método de enseñanza de una lengua extranjera a adultos.

Due to changes in the climate and the existence of a wide range of Asparagus officinalis L. cultivars, it is necessary to identify their suitability for cultivation in Poland and investigate their susceptibility to infection by the most common pathogens. The identification of the species composition of fungi of the Fusarium genus found in green spears of edible A. officinalis cultivars and the factors contributing to their occurrence will enable the effective protection of these crops. The study was conducted on seven A. officinalis cultivars bred in different countries, which were dioecious cultivars with male and female specimens: ‘Ariane’ (Germany), ‘Cipres’ (France), ‘Eposs’ (Germany), as well as cultivars with male specimens only: ‘Andreas’ (France), ‘Gynlim’, ‘Grolim’ (Netherlands), and ‘Hannibal’ (Germany). The analysis of the composition of the fungi isolated from the green A. officinalis spears showed that most of the isolates belonged to the Fusarium genus (F. culmorum Wm.G. Sm., F. equiseti (Corda) Sacc., F. oxysporum Schltdl., F. proliferatum (Matsush.) Nirenberg ex Gerlach & Nirenberg, F. solani (Mart.) Sacc., and F. fujikuroi Nirenberg). Other fungal species (Alternaria, Botrytis, Cladosporium, Penicillium, and Stemphylium) were rarely isolated. The majority of the Fusarium genus isolates came from the spears of the ‘Ariane’ and ‘Eposs’ cultivars showing disease symptoms and from the spears of the ‘Grolim’ cultivar without showing disease symptoms. The fungi of the Fusarium genus colonised both the spears with and without disease symptoms, but there were always more isolates on the ones with disease symptoms. Fungi of the Fusarium genus occurred more often in the epidermis than in the parenchyma. F. oxysporum was the dominant fungus in the A. officinalis spears under analysis. The number of fungi isolates of the Fusarium genus collected from the green A. officinalis spears tended to increase at the consecutive harvest dates, which means that the spears harvested at the latest date (late June) were the most heavily colonised by fungi. All of the fungi isolates of the Fusarium genus collected from the spears exhibited pathogenicity against A. officinalis plants.

Aim of the study. The profession of a physiotherapist is still at the stage of shaping and strengthening its position, both in the group of medical professions and in social awareness. The study aimed to assess the scope of use and satisfaction with physiotherapy services provided as part of public and private health care. Matherials and methods. The study covered a total of 606 people (100%). The vast majority were women (506; 83.5%). The research tool was an original questionnaire made available via a Google form. The survey consisted of 35 questions, 5 of which concerned some socio-demographic characteristics. Results. Most of the respondents used commercial services financed from their own budget (258; 78.2%). The most frequently indicated criterion for selecting a public institution was the distance from the place of residence (97; 16,1%), and a private one – the opinion of friends (159; 26,24%). The largest number of respondents using physiotherapeutic services would choose commercial services if they had to be used again (224; 67.9%). Conclusions. More than half of the surveyed people used the services provided by a physiotherapist, moreover vast majority of respondents used commercial services, financed from their resources. Criteria for selecting public and private institutions were varied and the assessed satisfaction with commercial physiotherapeutic services was higher than public.

Oncogenic RAS-induced senescence (OIS) is an autonomous tumour suppressor mechanism associated with pre-malignancy1-3. Achieving this phenotype typically requires a high level of oncogenic stress, yet the phenotype provoked by lower oncogenic dosage remains unclear. Here we develop oncogenic RAS-dose escalation models in vitro and in vivo, revealing a RAS-dose-driven non-linear continuum of downstream phenotypes. In a hepatocyte OIS model in vivo, where ectopic expression of NRASG12V fails to induce tumours in part due to OIS-driven immune clearance4. scRNA-seq analyses reveal distinct hepatocyte clusters with typical OIS or progenitor-like features, corresponding to high- and intermediate-NRASG12V levels, respectively. Remarkably, when titered down, NRASG12V-expressing hepatocytes become immune-resistant, and develop tumours. Time-series monitoring at single-cell resolution identifies two distinct tumour types: early-onset aggressive undifferentiated and late-onset differentiated hepatocellular carcinoma (HCC). The molecular signature of each murine tumour type is associated with different progenitor features and enriched in distinct human HCC subclasses. Our results define the oncogenic dosage-driven OIS spectrum, reconciling the senescence and tumour initiation phenotypes in early tumorigenesis.

Langya virus (LayV) is a paramyxovirus in theHenipavirusgenus, closely related to the deadly Nipah and Hendra viruses, that was identified in August 2022 through disease surveillance following animal exposure in eastern China. Paramyxoviruses present two glycoproteins on their surface, known as attachment and fusion proteins, that mediate entry into cells and constitute the primary antigenic targets for immune response. Here, we determine cryo-EM structures of the uncleaved LayV fusion protein (F) ectodomain in pre- and post-fusion conformations. The LayV-F protein exhibits pre- and post-fusion architectures that, despite being highly conserved across paramyxoviruses, show differences in their surface properties, in particular at the apex of the prefusion trimer, that may contribute to antigenic variability. While dramatic conformational changes were visualized between the pre- and post-fusion forms of the LayV-F protein, several domains remained invariant, held together by highly conserved disulfides. The LayV-F fusion peptide is buried within a highly conserved, hydrophobic, interprotomer pocket in the pre-fusion state and is notably less flexible than the rest of the protein, highlighting its “spring-loaded” state and suggesting that the mechanism of pre-to-post transition must involve perturbations to the pocket and release of the fusion peptide. Together, these results offer a structural basis for how the Langya virus fusion protein compares to its Henipavirus relatives and propose a mechanism for the initial step of pre- to post-fusion conversion that may apply more broadly to paramyxoviruses.ImportanceThe Henipavirus genus is quickly expanding into new animal hosts and geographic locations. This study compares the structure and antigenicity of the Langya virus fusion protein to other henipaviruses, which has important vaccine or therapeutic development implications. Furthermore, the study proposes a new mechanism to explain the early steps of the fusion initiation process that can be more broadly applied to theParamyxoviridaefamily.

Purpose of Review The compression therapy provides valuable support during management of vascular and inflammatory lower leg skin disorders. The review outlines the mechanism of action and the treatment options available with indications for use in wound management and general dermatology. Recent Findings Atypical wounds such as pyoderma gangrenosum, cutaneous vasculitis and other inflammatory skin diseases may benefit from the use of compression therapy. Adherence to treatment is always a challenging aspects for patients and caregiver, but modern technologies and specific materials have improved the compliance during treatment. Summary Compression therapy is a main option in vascular ulcer management. The technology provided by different devices together with new methods of bandaging application have increased the outcomes and acceptability from patients. Physicians should be aware of the advantages provided by compression therapy in skin diseases.

Supplementary Figure 1 from Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response

Supplementary Figure 6 from Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response

Supplementary Figure 4 from Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response

Supplementary Table 1, Methods and Materials, Figure Legends 1-6 from Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response

Supplementary Figure 5 from Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response

Photodynamic therapy (PDT) is an approved therapeutic procedure that exerts cytotoxic activity toward tumor cells by inducing production of reactive oxygen species such as singlet oxygen. PDT leads to oxidative damage of cellular macromolecules, including proteins that undergo multiple modifications such as fragmentation, cross-linking, and carbonylation that result in protein unfolding and aggregation. Because the major mechanism for elimination of carbonylated proteins is their degradation by proteasomes, we hypothesized that a combination of PDT with proteasome inhibitors might lead to accumulation of carbonylated proteins in endoplasmic reticulum (ER), aggravated ER stress, and potentiated cytotoxicity toward tumor cells. We observed that Photofrin-mediated PDT leads to robust carbonylation of cellular proteins and induction of unfolded protein response. Pretreatment of tumor cells with three different proteasome inhibitors, including bortezomib, MG132, and PSI, gave increased accumulation of carbonylated and ubiquitinated proteins in PDT-treated cells. Proteasome inhibitors effectively sensitized tumor cells of murine (EMT6 and C-26) as well as human (HeLa) origin to PDT-mediated cytotoxicity. Significant retardation of tumor growth with 60% to 100% complete responses was observed in vivo in two different murine tumor models (EMT6 and C-26) when PDT was combined with either bortezomib or PSI. Altogether, these observations indicate that combination of PDT with proteasome inhibitors leads to potentiated antitumor effects. The results of these studies are of immediate clinical application because bortezomib is a clinically approved drug that undergoes extensive clinical evaluations for the treatment of solid tumors. [Cancer Res 2009;69(10):4235–43]

Supplementary Figure 2 from Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response

Supplementary Figure 3 from Proteasome Inhibition Potentiates Antitumor Effects of Photodynamic Therapy in Mice through Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response

There is a strong interaction between the immunological and nervous system in the skin. Lesions that are physically disfiguring and chronically relapsing have a high impact on quality of life (QoL) and can result in the emergence of psychiatric disorders. The literature data confirm a higher prevalence of psychiatric disorders in patients with psoriasis, hidradenitis suppurativa (HS) and atopic dermatitis (AD), but such data are compromised by low-quality evidence due to methodological heterogeneity.The primary aim was to analyse the prevalence of psychiatric comorbidities in a group of psoriasis, AD and HS patients compared with a control group. The secondary aims were to evaluate the impact of psychiatric comorbidities on the disease development, severity, flare-ups and QoL.A total of 59 cases and 64 controls were included.Generalized anxiety disorder and depressive disorder with anxious distress were found to be risk factors for AD. Age, smoking and substance-related disorder showed a specific association with HS. Major depressive disorder showed a specific association with dermatology life quality index (DLQI) and all the above disease flare-ups.Atopic dermatitis, psoriasis and HS are associated with psychiatric disorders. A psychodermatological approach improves outcomes in terms of QoL, disease flare-ups and long-term management.

JanowskaMaria, Rogacka Karolina, PyrakBartłomiej, Kędziora–Kornatowska Kornelia. Health consequences of using special diets with restricted carbohydrate consumption.Journal of Education, Health and Sport. 2022;12(3):173-183.eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2022.12.03.015 https://apcz.umk.pl/JEHS/article/view/JEHS.2022.12.03.015 https://zenodo.org/record/6374571 The journal has had 40points in Ministry of Educationand Science of Poland parametric evaluation. Annex to the announcement of the Minister of Education and Science of December 21, 2021. No. 32343. Has a Journal's Unique Identifier: 201159. Scientific disciplines assigned: Physical Culture Sciences (Field of Medical sciences and health sciences); Health Sciences (Field of Medical Sciences and Health Sciences). Punkty Ministerialne z 2019 - aktualny rok40punktów. Załącznik do komunikatu Ministra Edukacji i Nauki z dnia 21 grudnia 2021 r.Lp. 32343. Posiada Unikatowy Identyfikator Czasopisma: 201159. Przypisane dyscypliny naukowe:Nauki o kulturze fizycznej (Dziedzina nauk medycznych i nauk o zdrowiu);Nauki o zdrowiu (Dziedzina nauk medycznych i nauk o zdrowiu). © The Authors 2022; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 01.03.2022. Revised: 16.03.2022. Accepted: 21.03.2022. Health consequences of using special diets with restricted carbohydrate consumption Maria Janowska1, ORCID: 0000-0003-0653-4428, marysia.janowska97@wp.pl Karolina Rogacka2,ORCID: 0000-0001-9925-7305, karolinarogacka2697@gmail.com Bartłomiej Pyrak3, ORCID: 0000-0003-3489-2353, b.pyrak12@gmail.com Kornelia Kędziora–Kornatowska2, ORCID: 0000-0003-4777-5252, kornelia.kornatowska@cm.umk.pl 1 Department of Dietetic, Chair of Dietetic, Institute of Human Nutrition Sciences, Warsaw University of Life Sciences-SGGW 2Department of Geriatrics, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun 3 Departament of Physical Pharmacy, Faculty of Pharmacy, Medical University of Warsaw ABSTRACT Introduction and purpose: There are many reasons why patients with specific health disorders, as well as people in good health, decide to follow special diets. Often their choice falls on dietary models that include limited carbohydrate intake. The most popular in this area are low-carbohydrate and high-protein diets, which have a significant impact on metabolism, making them of particular interest to people with excessive body weight. State of knowledge: Low-carbohydrate diets include many dietary models of varying restrictiveness, with or without achieving a state of ketosis. The ketogenic diet has the most promising clinical results in terms of effects on carbohydrate and fat metabolism. Long-term studies are still too few and inconsistent, also regarding the effects on weight loss compared to traditional approach. High-protein diets also include a reduction in carbohydrate intake, but with a higher proportion of protein in the total diet energy content. Observations on the effect of weight reduction and metabolic modification are inconsistent. The possible multi-directional negative health effects seem to be a strong argument against this approach and its recommendation. Conclusion: The basis of any reduction diet must be a reduced energy supply. This can be achieved in a variety of ways, which are designed to facilitate its implementation by patients, as well as to have the most beneficial effect on their impaired metabolism. Diversions from the traditional approach may have beneficial effects, but may also contribute to other health problems. It is important to consider the patients' health status as a whole, and to ensure specialist follow-up when using described special diets, because of possible side effects and difficulties in properly balancing the diet. They can only be recommended in specific cases, with a protein-rich diet appearing particularly dangerous. The standard in the management of excessive body weight remains the traditional approach, the effects of which are well documented and do not represent risk factors for other conditions. Key-words: special diets; low-carbohydrate diet; high-protein diet; weight loss

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder characterized by pancytopenia, splenomegaly and increased susceptibility to infections. In 2011, BRAF gene mutation was identified in almost all the patients with the classical type of HCL. The purine analogs cladribine and pentostatin induce long-term remission in the majority of patients, and they remain the standard treatment for this type of leukemia. However, more than half of patients in complete response relapse over the long term, with a quarter of them relapsing within the first five years. Recently, new drugs have been developed and have demonstrated efficacy in refractory or relapsed HCL. The immunotoxin Moxetumomab pasudotox was registered for HCL in 2018. The BRAF kinase inhibitors vemurafenib and dabrafenib, as well as the Bruton kinase inhibitor ibrutinib, are also proven highly effective in clinical trials.

Activities in the area of cultural policy (CP) are usually equated with the activities of the state and its institutions. Also, many definitions and concepts indicate such an understanding of this concept. Meanwhile, the implementation of cultural policy involves – in different ways – entities belonging to all three sectors: public, private, and third sector. They participate in the design of activities, their implementation, analysis of challenges and scenarios, as well as in the evaluation of results. The aim of this article is firstly to present the concepts and approaches to CP, and secondly to diagnose the areas and phases of social economy entities' activities in relation to CP.

Atopic dermatitis is a chronic inflammatory skin disease significantly affecting patients’ and their parents’ lives. Mothers are mostly responsible for the long-term treatment and their wellbeing is essential. The major objective of this cross-sectional study was to investigate the relationship between atopic dermatitis in children, especially concomitant itch, and the quality of life, stress, sleep quality, anxiety, and depression of their mothers. The study included 88 mothers of children with atopic dermatitis and 52 mothers of children without atopic dermatitis. All mothers completed sociodemographic questionnaire, the Perceived Stress Scale, the Athens Insomnia Scale and the Hospital Anxiety and Depression Scale. Additionally, mothers of children with atopic dermatitis filled in the Family Dermatology Life Quality Index. The severity of atopic dermatitis and pruritus intensity were evaluated by the Scoring Atopic Dermatitis Index and the Numerical Rating Scale, respectively. The severity of atopic dermatitis and itch significantly correlated with the quality of life, insomnia, and perceived stress of the mothers. Mothers whose children had had atopic dermatitis for more than 6 months had significantly higher scores of anxiety and depression. The results highlight the importance of screening mothers for functional impairment to provide adequate support. More attention should be directed to the standardization of stepped care interventions addressing factors resulting in the impaired functioning of mothers.

Recent estimates have placed the number of new human immunodeficiency virus type 1 (HIV-1) infections at approximately 1.5 million per year, emphasizing the ongoing and urgent need for an effective vaccine. The envelope (Env) glycoprotein is the main focus of HIV-1 vaccine development, but, due to its inherent metastability, many Env variants are difficult to recombinantly express in the relatively large quantities that are required for biochemical studies and animal trials.

G protein-coupled receptor 17 (GPR17) and the WNT pathway are critical players of oligodendrocyte (OL) differentiation acting as essential timers in developing brain to achieve fully-myelinating cells. However, whether and how these two systems are related to each under is still unknown. Of interest, both factors are dysregulated in developing and adult brain diseases, including demyelination disorders and cancer, making the understanding of their reciprocal interactions of potential importance for identifying new targets and strategies for myelin repair. Here, we examined regulatory mechanisms linking WNT signalling to GPR17 expression in OLs. We analyzed the relative expressions of mRNAs encoding GPR17 and the T cell factor/Lymphoid enhancer-binding factor-1 (TCF/LEF) transcription factors of the canonical WNT/b-CATENIN pathway in both PDGFRa+ and O4+ OLs during mouse post-natal development. In O4+ cells, Gpr17mRNA level peaked at post-natal day 14 and then decreased concomitantly to the physiological uprise of WNT tone, as shown by increasedLef1 mRNA level. The link between WNT signaling and GPR17 expression was further reinforced in vitro in primary PDGFRa+ cells and in the Oli-neu cell line. High WNT tone impaired OL differentiation and drastically reduced GPR17 mRNA and protein levels. In Oli-neu cells, we demonstrated that WNT/b-CATENIN activation represses Gpr17 promoter activity through both putative WNT response elements (WRE) and upregulation of the inhibitor of DNA-binding protein 2 (Id2). We conclude that WNT pathway influences oligodendrocyte maturation by repressing GPR17 which could have implications in pathologies characterized by dysregulations of the oligodendroglial lineage including multiple sclerosis and oligodendroglioma.

BackgroundJanus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed studies investigating the effects of different JAK inhibitors on B cells are missing. Within this study, we therefore aimed to characterize the effect of JAK inhibition on the B cell compartment.MethodsTo this end, we investigated the B cell compartment under JAK inhibition and compared the specific effects of the different JAK inhibitors tofacitinib (pan-JAK), baricitinib (JAK1/2), ruxolitinib (JAK1/2), upadacitinib (JAK1/2) as well as filgotinib (selective JAK1) on in-vitro B cell activation, proliferation, and class switch recombination and involved pathways.ResultsWhile B cell phenotyping of RA patients showed an increase in marginal zone (MZ) B cells under JAK inhibition, comparison with healthy donors revealed that the relative frequency of MZ B cells was still lower compared to healthy controls. In an in-vitro model of T-cell-independent B cell activation we observed that JAK1/2 and selective JAK1 inhibitor treatment led to a dose-dependent decrease of total B cell numbers. We detected an altered B cell differentiation with a significant increase in MZ-like B cells and an increase in plasmablast differentiation in the first days of culture, most pronounced with the pan-JAK inhibitor tofacitinib, although there was no increase in immunoglobulin secretion in-vitro. Notably, we further observed a profound reduction of switched memory B cell formation, especially with JAK1/2 inhibition. JAK inhibitor treatment led to a dose-dependent reduction of STAT3 expression and phosphorylation as well as STAT3 target gene expression and modulated the secretion of pro- and anti-inflammatory cytokines by B cells.ConclusionJAK inhibition has a major effect on B cell activation and differentiation, with differential outcomes between JAK inhibitors hinting towards distinct and unique effects on B cell homeostasis.

SUMMARYThe CD4 binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the CD4bs is occluded by glycans, immunogen expansion of appropriate naïve B cells, and selection of functional antibody mutations. Here, we demonstrate immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAbs bound to HIV-1 Env demonstrated binding angles similar to human bnAbs and heavy chain second complementarity determining region-dependent binding characteristic of all known human CD4-mimicking bnAbs. Macaque nAbs were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAbs. This vaccine study initiated the B cells from which derive CD4bs bnAbs in primates, accomplishing the key first step in development of an effective HIV-1 vaccine.

La mimesi come termine teorico e letterario si è formata già nell'antichità. Tentativi di definirlo sono già stati fatti da Platone nei suoi dialoghi, mentre fu solo Aristotele nella sua congeniale Poetica a formulare questo argomento in modo tale da diventare la base di discussioni e indagini scientifiche, molte delle quali continuano ancora oggi. La creatività mimetica ha dominato l'arte per centinaia di anni, raggiungendo l'apice della popolarità a cavallo tra il XIX e il XX secolo (sebbene siano emerse e funzionassero tendenze precedenti che quasi programmaticamente deviassero da questo percorso creativo; un esempio può essere l'arte dell'era romantica con tutti suoi aspetti mistici). Nel XX secolo, l'arte ha iniziato a cambiare in modo molto dinamico, seguendo lo sviluppo industriale e tecnologico incredibilmente rapido in Europa e nel mondo. Questo, a sua volta, ha portato allo sviluppo dinamico di nuove tendenze, nuovi modi di pensare l'arte.

Pesticides account for hundreds of millions of cases of acute poisoning worldwide each year, with organophosphates (OPs) being responsible for the majority of all pesticide-related deaths. OPs inhibit the enzyme acetylcholinesterase (AChE), which leads to impairment of the central- and peripheral nervous system. Current standard of care (SOC) alleviates acute neurologic-, cardiovascular- and respiratory symptoms and reduces short term mortality. However, survivors often demonstrate significant neurologic sequelae. This highlights the critical need for further development of adjunctive therapies with novel targets. While the inhibition of AChE is thought to be the main mechanism of injury, mitochondrial dysfunction and resulting metabolic crisis may contribute to the overall toxicity of these agents. We hypothesized that the mitochondrially targeted succinate prodrug NV354 would support mitochondrial function and reduce brain injury during acute intoxication with the OP diisopropylfluorophosphate (DFP). To this end, we developed a rat model of acute DFP intoxication and evaluated the efficacy of NV354 as adjunctive therapy to SOC treatment with atropine and pralidoxime. We demonstrate that NV354, in combination with atropine and pralidoxime therapy, significantly improved cerebral mitochondrial complex IV-linked respiration and reduced signs of brain injury in a rodent model of acute DFP exposure.

Treatment of chronic leg ulcers remains a major challenge and it is a substantial financial burden on individuals, families, caregivers, and health care system. There is increasing evidence on using of autologous Platelet-rich-plasma in wound repair but limited clinical data are available on the efficacy and safety of the use of umbilical cord blood platelet gel (CBPG). In our pilot study, for the first time, we aimed to evaluated the safety and efficacy of the use of umbilical CBPG combined with a hydrogel dressing in 10 patients with chronic venous ulcers (VU). The protocol consisted of application of umbilical cord blood platelet-rich plasma (PRP) combined with a Carboxymethyl cellulose (CMC)-based hydrogel dressing once a week for 4 weeks. The 80% of patients after 4 weeks of treatment had a significantly decrease in wound size. Moreover, we obtained an improvement in terms of mean Wound Bed Score (WBS), numeric rating scale (NRS) value and the EQ-5D index score. This pilot study showed that the topically therapeutic administration of umbilical CBPG associated with a CMC-based hydrogel dressing has the potential to accelerate the healing of chronic lesions without adverse reaction. However, additional studies with larger sample size and longer follow-up periods are required to confirm our findings.

The pathogenesis of biliary atresia (BA) is still not clear. The aim of this study was to evaluate the expression of selected immunological parameters in liver tissue in BA children based on CMV/EBV infection status. Eight of thirty-one children with newly diagnosed BA were included in this prospective study and assigned to two groups (I with active infection, II without active or past infection). All studies were performed on surgical liver biopsies. To visualize CD8+ T cells and CD56 expression, immunohistochemical staining was performed. The viral genetic material in the studied groups was not found, but CMV infection significantly affected the number of CD8+ lymphocytes in both the portal area and the bile ducts. The average number of CD8+ cells per mm2 of portal area in Groups I and II was 335 and 200 (p = 0.002). The average number of these cellsthat infiltrated the epithelium of the bile duct per mm2 in Group I and II was 0.73 and 0.37 (p = 0.0003), respectively. Expression of CD56 in the bile ducts corresponded to the intensity of the inflammatory infiltrate of CD8+ cells. Our results suggest that active CMV infection induces an increased infiltration of CD8+ lymphocytes, which could play a role in BA immunopathogenesis. Increased CD56 expression can be a sign of a newly formed bile structure often without lumen, suggesting inhibition of the maturation process in BA.

In the last few years, rare-earth-doped upconverting nanoparticles (UCNPs) have been widely used in different life sciences due to their unique properties. Nanoparticles have become a multifunctional and promising new approach to neurobiological disorders and have shown extraordinary application potential to overcome problems related to conventional treatment strategies. This study evaluated the internalization mechanisms, bio-distribution, and neurotoxicity of NaYF4:20%Yb3+,2%Er3+ UCNPs in rat organotypic hippocampal slices. TEM results showed that UCNPs were easily internalized by hippocampal cells and co-localized with selected organelles inside neurons and astrocytes. Moreover, we found that UCNPs were taken into the neurons via clathrin- and caveolae-mediated endocytosis. Propidium iodide staining and TEM analysis did not confirm the adverse effects of UCNPs on hippocampal slice viability and morphology. Therefore, UCNPs may be a potent tool for bio-imaging and testing new therapeutic strategies for brain diseases in the future.

Lata 70.–80. XX w. to czas światowej rewolucji, przebudowującej sferę stosunków pracy, prowadzącej do zasadniczej zmiany roli człowieka w procesie pracy. Był to rezultat buntu świata pracy wobec pracy w „okruchach”, wyniszczającej psychicznie i fizycznie coraz lepiej wykształconego uczestnika procesu pracy. Nastąpiła naukowo udowodniona „ucieczka” od pracy rozdrobnionej, monotonnej, degradującej pracownika do pracy, w której dzięki uzyskanej autonomii mógł decydować o zakresie i sposobie wykonywanej pracy indywidualnej i grupowej. Celem artykułu jest prezentacja światowych i polskich osiągnięć w sferze humanizowania pracy, przywracającej pełnienie podmiotowej roli wykonawcy procesu pracy. Podjęto również próbę poszukiwania korzeni dla rozwoju zarządzania zasobami ludzkimi w Polsce. Wskazuje się tutaj różnice między dorobkiem światowym a polskim, którego rozwój przypadał na okres kryzysu gospodarczego i buntu społecznego. Mimo to w ostatecznym rozrachunku należy uznać, że realizowane rozwiązania organizacyjne w naszym kraju (często sterowane odgórnie) miały pożądany wydźwięk humanizacyjny. Duży udział w tym względzie miała determinacja przedstawicieli nauki, którym od początku przyświecała idea humanizacji pracy

SARS-CoV-2 spike mRNA vaccines1–3 mediate protection from severe disease as early as ten days after prime vaccination3, when neutralizing antibodies are hardly detectable4–6. Vaccine-induced CD8+ T cells may therefore be the main mediators of protection at this early stage7,8. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. Here we show on a single-epitope level that a stable and fully functional CD8+ T cell response is vigorously mobilized one week after prime vaccination with bnt162b2, when circulating CD4+ T cells and neutralizing antibodies are still weakly detectable. Boost vaccination induced a robust expansion that generated highly differentiated effector CD8+ T cells; however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared with natural infection, vaccine-induced early memory T cells exhibited similar functional capacities but a different subset distribution. Our results indicate that CD8+ T cells are important effector cells, are expanded in the early protection window after prime vaccination, precede maturation of other effector arms of vaccine-induced immunity and are stably maintained after boost vaccination.

Vascular malformations are present in a great variety of congenital syndromes, either as the predominant or additional feature. They pose a major challenge to the clinician: due to significant phenotype overlap, a precise diagnosis is often difficult to obtain, some of the malformations carry a risk of life threatening complications and, for many entities, treatment is not well established. To facilitate their recognition and aid in differentiation, we present a selection of notable congenital disorders of vascular system development, distinguishing between the heritable germinal and sporadic somatic mutations as their causes. Clinical features, genetic background and comprehensible description of molecular mechanisms is provided for each entity.

This article summarizes the main epidemiologic and diagnostic features of seborrheic keratosis-like (SK-like) melanoma. We performed a review of the current literature. The real and current incidence and prevalence of SK-like melanoma are unknown. Many lesions are misdiagnosed and not excised with histopathologic confirmation, or excised without an appropriate surgical approach due to a benign clinical and dermoscopic appearance. SK-like melanoma presents both melanoma and SK features. SK-like melanoma and SK are often clinically indistinguishable even for experienced dermatologists. Clinically, it develops as a black-dark brown or light slightly elevated, papule, nodule or plaque with rapid growth and a regular or irregular shape. SK-like melanoma presents melanocytic and nonmelanocytic dermoscopic features. Irregular dark-brown dots/globules, a blue-grayish veil, streaks, irregular pigmentation or network and brown lines point to a melanoma diagnosis. Among the nonmelanocytic features, milia-like cysts and comedo-like openings have been highlighted. The association of polarized and nonpolarized dermoscopic techniques is more accurate for studying the dermoscopic features of SK-like melanoma. If the dermoscopic features are unclear, further investigations with reflectance confocal microscopy (RCM) or biopsy with histologic examination are essential. SK-like melanoma is a dermatologic challenge. Careful clinical and dermoscopic evaluation favor a correct diagnosis. In unclear cases, it is important to perform a biopsy with histologic examination to confirm the correct diagnosis.