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Fenestrations in liver sinusoidal endothelial cells (LSEC) are transcellular nanopores of 50–350 nm diameter that facilitate bidirectional transport of solutes and macromolecules between the bloodstream and the parenchyma of the liver. Liver diseases, ageing, and various substances such as nicotine or ethanol can negatively influence LSECs fenestrations and lead to defenestration. Over the years, the diameter of fenestrations remained the main challenge for imaging of LSEC in vitro. Several microscopy, or rather nanoscopy, approaches have been used to quantify fenestrations in LSEC to assess the effect of drugs and, and toxins in different biological models. All techniques have their limitations, and measurements of the “true” size of fenestrations are hampered because of this. In this study, we approach the comparison of different types of microscopy in a correlative manner. We combine scanning electron microscopy (SEM) with optical nanoscopy methods such as structured illumination microscopy (SIM) or stimulated emission depletion (STED) microscopy. In addition, we combined atomic force microscopy (AFM) with SEM and STED, all to better understand the previously reported differences between the reports of fenestration dimensions. We conclude that sample dehydration alters fenestration diameters. Finally, we propose the combination of AFM with conventional microscopy that allows for easy super-resolution observation of the cell dynamics with additional chemical information that can be traced back for the whole experiment. Overall, by pairing the various types of imaging techniques that provide topological 2D/3D/label-free/chemical information we get a deeper insight into both limitations and strengths of each type microscopy when applied to fenestration analysis.

Abstract Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mechanisms. One of the major concerns is raised by the contradictory data supporting or denying the presence of ACE2, the SARS-CoV-2 binding receptor, on the EC surface. Here, we show that primary human pulmonary artery ECs possess ACE2 capable of interaction with the viral Spike protein (S-protein) and demonstrate the crucial role of the endothelial glycocalyx in the regulation of the S-protein binding to ACE2 on ECs. Using force spectroscopy method, we directly measured ACE2- and glycocalyx-dependent adhesive forces between S-protein and ECs and characterized the nanomechanical parameters of the cells exposed to S-protein. We revealed that the intact glycocalyx strongly binds S-protein but screens its interaction with ACE2. Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.

The aim of the article is to identify the influence of the first months of Russian aggression against Ukraine on the recruitment plans of enterprises in the country receiving refugees, as exemplified by the Polish case study. Quantitative research was conducted among 500 Polish enterprises. Based on monthly measurements, before and after the outbreak of war in Ukraine, information was received from enterprises on their plans related to recruitment, including Ukrainian workers. Additionally, secondary data available from public databases was analysed. Clustering methods were used to analyse the dynamics and structure of the data gathered from the enterprises. Correspondence analysis was implemented to visualize the relationship between the structure of enterprises and recruitment decisions. The war in Ukraine influenced a deterioration of operating conditions for Polish companies. Regardless of the barriers faced by the companies, in April 2022, all enterprises willing to increase employment were thinking of hiring refugees from Ukraine. Such targeted demand from employers created the conditions for the rapid labour activation of refugees. [ABSTRACT FROM AUTHOR]

The article presents a study which investigated growth in the share of the high-need population that can benefit from home-based primary care (HBPC) and whether there has been corresponding growth in receipt of HBPC. Topics discussed include growth in the number of Independence at Home-qualifying (IAHQ) traditional Medicare (TM) beneficiaries from 2014 to 2021, reason that nearly 90 percent of IAHQ beneficiaries in 2021 did not receive HBPC, and limited access to value-based payment models.

Góra Moria jest znana przede wszystkim jako Wzgórze Świątynne w Jerozolimie. Zarówno Stary, jak i Nowy Testament wspominają o niej wielokrotnie, jednak w zdecydowanej większości przypadków nie wymieniają jej z nazwy, lecz utożsamiają ją ze Świątynią Jerozolimską. Etymologia nazwy Moria możliwa jest do wyprowadzenia z rdzeni zarówno hebrajskich, jak i aramejskich. Odsłania ona zabiegi literackie, które mogą dawać możliwości nowych interpretacji znaczenia tego miejsca. Artykuł ukazuje te zabiegi, a także przedstawia wyniki badań archeologicznych tego miejsca.

Mucormycosis is a rare but a devastating and lifethreatening fungal infection caused by fungi of the order Mucorales usually in immunocompromised patients. Depending on the organs and tissues involved, there are sinus, pulmonary, gastrointestinal, orbital, cerebral, cutaneous and disseminated mucormycosis. Only sporadic cases of hepatic mucormycosis have been described. Hence, we present a complicated treatment management in a 16-month-old child with leukemia and generalized mucormycosis localized in the liver and in the gastrointestinal tract. The collaboration of a multidisciplinary team and appropriate therapy gave a chance not only to save the patient's life, but to carry out anticancer treatment, which resulted in leukemia remission. A 6-month course of isavuconazole and amphotericin B liposomal as well as surgical treatment led to the cure of the fungal infection.

Rosacea is a chronic dermatosis, manifesting with erythema, papular or pustular eruptions located in the facial area. The authors present a case of an 84-year-old woman with a long-term history of rosacea who had a mycotic infection of the facial skin imitating aggravation of the underlying disease. The case presented by us can be regarded as a variant of “tinea incognito”, i.e., undiagnosed mycosis, misdiagnosed as another dermatosis, which is often aggravated by the patient by using local glucocorticosteroids or other local immunomodulators, which hinders proper diagnosis. It may be diagnostically relevant to consider other comorbidities in elderly patients with rosacea.

Long-acting injectable (LAI) neuroleptics constitute an effective therapeutical alternative for individuals suffering from persistent mental illness. These injectable pharmaceuticals help patients manage their condition better and improve long-term outcomes by preventing relapses and improving compliance. This review aims to analyse the current formulation aspects of LAI neuroleptics, with particular emphasis on analysis of drug release profiles as a critical test to guarantee drug quality and relevant therapeutical activity. While there is no officially approved procedure for depot parenteral drug formulations, various dissolution tests which were developed by LAI manufacturers are described. In vitro dissolution tests also possess a critical function in the estimation of the in vivo performance of a drug formulation. For that reason, thorough inspection of the in vitro–in vivo correlation (IVIVC) is also discussed. [ABSTRACT FROM AUTHOR]

Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants. Two de novo heterozygous variants, c.227T>G p.(L76R) or c.227T>C p.(L76P) in TMEM163 were identified in two unrelated HLD patients. TMEM163 protein is a zinc efflux transporter localized within the plasma membrane, lysosomes, early endosomes, and other vesicular compartments. It has not been associated with hypomyelination. Functional zinc flux assays in HeLa cells stably-expressing TMEM163 protein variants, L76R and L76P, revealed distinct attenuation or enhancement of zinc efflux, respectively. Experiments using a zebrafish model with knockdown of tmem163a and tmem163b (morphants) showed that loss of tmem163 causes dysplasia of the larvae, locomotor disability and myelin deficit. Expression of human wild type TMEM163 mRNAs in morphants rescues the phenotype, while the TMEM163 L76P and L76R mutants aggravated the condition. Moreover, poor proliferation, elevated apoptosis of oligodendrocytes, and reduced oligodendrocytes and neurons were also observed in zebrafish morphants. Our findings suggest an unappreciated role for TMEM163 protein in myelin development and add TMEM163 to a growing list of genes associated with hypomyelination leukodystrophy.

Book Review: Wojciech Węgrzyniak, Psalm 83. Teksty – egzegeza – konteksty (Studia Biblica Lublinensia 19; Lublin: Wydawnictwo KUL 2019). Ss. 381. PLN 27.00. Oprawa miękka. ISBN 978-83-8061-678-3

Due to increasing resistance of pathogenic fungi to antifungal treatments, new types of drugs are needed. For this purpose, active substances with antifungal properties occurring in natural compounds should be considered. The herb Psephellus bellus shows strong antifungal activity and is characterized by unique guaianolides, which have an ester on C-2. Thus, a specialized method of isolation and testing was applied to assess the pharmacological effects of these guaianolides. After phytochemical analysis (chromatography and spectral methods), selected lipophilic compounds and the herb extract of this species containing 26 sesquiterpene lactones were tested. The antifungal effect of the herbal compounds was determined on clinical strains of fungi Candida, Rhodotorula, Trichophyton, Microsporum, and Scopulariopsis using a diffusion test. The MTT assay was employed to study the cytotoxic effects of the extract against human fibroblasts. Statistical analysis was performed. All analyzed compounds exhibited antifungal activity in cultivations suitable for assessment. Most lipophilic cebellins from Psephellus bellus prevent the growth of most fungal strains.

Introduction. The superficial mycoses remain a group of diseases of public health significance. The increased incidence of mycoses is related, among other factors, to deficiency of the immune system, coexisting systemic and dermatological diseases, long-term, non-target antibiotic therapy and the increase in the number of people at risk of immunosuppression. Objective. To analyze the etiology and epidemiology of mycosis in patients under 18 years of age in the years 2013–2016 diagnosed in the Unit of Medical Mycology at the Department of Dermatology, Poznan University of Medical Sciences. Material and methods . A retrospective, etiological and epidemiological analysis was performed on the incidence of superficial mycosis in 295 patients under 18 years of age diagnosed in the years 2013–2016 in the Unit of Medical Mycology at the Department of Dermatology, Poznan University of Medical Sciences. Results . The study group included mostly cases of dermatophytic superficial mycosis of the scalp with prevalent zoophilic species, including Microsporum canis as the most common. Conclusions. Superficial mycoses are common during childhood. Increased incidence of certain forms of superficial mycoses in children has been observed, for example infections transmitted from exotic animals or onychomycosis.