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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.

Dermatophytosis is a superficial fungal skin infection common in humans around the world and is one of the many zoonotic skin diseases that cat owners are at risk of contracting. This retrospective study was conducted based on a detailed analysis of the results of mycological examination and medical documentation of 56 patients diagnosed with cat-to-human dermatophytoses from January 2017 to July 2022. Zoonotic mycoses were diagnosed more frequently in young people and women. In children, lesions most often occurred in the scalp area, and in adults, in the glabrous skin area. Skin infections caused by Microsporum canis (M. canis) prevailed and were confirmed in 47 patients (83.9%). Trichophyton mentagrophytes (T. mentagrophytes) was found in nine (16.1%) patients. M. canis predominantly caused infections of the scalp, followed by lower limb infections. Hairy scalps were almost exclusively involved in children. The odds of diagnosing M. canis infection compared to T. mentagrophytes infection was significantly higher in the head than in other regions, especially among children. The positive predictive value of a direct macroscopic examination was relatively low. [ABSTRACT FROM AUTHOR]

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

This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper arms. Regarding commensal interactions, Malassezia utilises nutrient sources without affecting the human host. In cases of pathogenicity, Malassezia can directly harm the host via virulence factors or toxins, or indirectly by triggering damaging host responses. The diagnosis typically relies on recognising characteristic clinical features. Due to the wide variability in its clinical presentation, recognising the differential diagnosis is critical. In this paper, we discuss the clinical differentials, with their dermatoscopic presentation, but also describe a range of helpful diagnostic techniques (microscopy, conventional and ultraviolet-induced fluorescence dermatoscopy, and confocal microscopy). Topical therapies are the primary treatment for PV, encompassing non-specific antifungal agents like sulphur with salicylic acid, selenium sulphide 2.5%, and zinc pyrithione. Additionally, specific topical antifungal medications with either fungicidal or fungistatic properties may also be incorporated into the topical treatment regimen, such as imidazoles, allylamines, and ciclopirox olamine. Systemic therapies might occasionally be used. Patient education and the promotion of good personal hygiene are pivotal to reduce the risk of recurrence. In recurrent cases, particularly during warmer and more humid periods, prolonged prophylaxis with topical agents should be considered. [ABSTRACT FROM AUTHOR]

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.

Nearly two decades of research on the host-pathogen interaction in fusiform rust of loblolly pine is detailed. Results clearly indicate that pathotype-specific genes in the host interacting with pathogen avirulence cause resistance as defined by the non-gall phenotype under favorable environmental conditions for disease development. In particular, nine fusiform rust resistance genes (Fr genes) are described here including the specific methods to determine each and their localization on the reference genetic map of loblolly pine. Understanding how these and other apparent Fr genes in loblolly pine and other rust-susceptible pines impact resistance screening, parental and progeny selection, and family and clonal deployment is an important area in forest genetics research and operational tree breeding. The documentation of these Fr genes is a key piece of information towards gaining that understanding and ultimately improving breeding and deployment strategies.

Artykuł przedstawia ogólną charakterystykę diagnostyki luf armat czarnoprochowych. Do badań zastosowano metodę wizualną opartą o wykorzystanie jednego z rodzajów endoskopu jakim jest wideoendoskop. W artykule opisano stanowisko wideoendoskopowe wykorzystywane do badań i diagnostyki różnego rodzaju luf. Diagnostyka stanu technicznego luf armat czarnoprochowych w postaci wizualnych badań nieniszczących pozwala na kompleksową wizualizację powierzchni wewnętrznej badanej lufy. Dodatkowe wyposażenie w połączeniu z oprogramowaniem pozwala dokładnie zwymiarować wykryte nieciągłości zarówno liniowe, jak i powierzchniowe. Ostatecznie badanie takie, pozwala na określenie stanu technicznego badanej lufy i jej zdatności do dalszej eksploatacji. W artykule przedstawiono obrazy z badań luf czarnoprochowych, ich stan powierzchni bezpośrednio po eksploatacji (po strzelaniu) i stan wewnętrznej powierzchni lufy wyczyszczonej i przygotowanej do badań. Visual testing internal area barrels black powder Abstract The article presents the general characteristics of diagnostic barrels of black powder guns. The study’s method was used for visual based on the use of one of the endoscope that is the videoendoscope. The article describes the position video endoscopes used for research and diagnosing various types of barrels. Diagnostics of technical condition of the barrels of guns black powder in the form of visual NDT allows for complete visualization of the surface of the inner barrel studied. Additional equipment in conjunction with the software allows accurate - not dimensioned detected discontinuities both linear and super- ficial. Finally, such an examination, allows you to determine the status of the technical study of the barrel and its suitability for further use. The article presents images from the barrels of black powder research, their surface condition immediately after use (after the shooting) and the condition of the inner surface of the barrel cleaned and prepared for testing.

The goal of the project examined here was to establish performance standards for Navy aerographer's mate (AG) enlisted sailors at three skill levels. We used an online expert judgment task and consensus workshop methodology to gather information from subject matter experts on minimal proficiency requirements for each task within each skill level. Analysis of these judgments found a high degree of rater agreement on these standards, and resolution of any disagreements was accomplished in a consensus workshop. (Contains 4 tables.)

Childhood injuries lead to increased morbidity and result in significant costs to public insurance programs. People with mental retardation, most of whom are covered by Medicaid, are at high risk for injury, which has implications for community inclusion, a central policy goal. Medicaid data from inpatient, outpatient, and long-term care settings represent an important new resource for injury surveillance in this population. Injury prevalence for 8.4 million Medicaid-eligible children in 26 states was measured using 1999 eligibility and claims data; 36.9% Medicaid beneficiaries ages 1 to 20 with mental retardation had at least one injury claim as compared with 23.5% of those without mental retardation. Prevalence rates are reported by gender and age for a variety of injury types.

The biomaterial surface can be essentially upgraded with the therapeutic function by the introduction of controlled, local elution of biologically active molecules. The use of ultrasonic-assisted formation of nanoparticles with controlled size and morphology can be readily utilized for such functionalization. In this study, the synthesis route for the generation of nanoparticles of fluorouracil, the bioactive molecule used in anticancer therapy, was reported. The tandem of experimental (TEM, NTA, ATR-IR) and computational (MD simulations) approaches allowed us to obtain a molecular-level picture of the cavitation bubble interface where the enrichment of fluorouracil molecules takes place. Thanks to the originally developed computational model of cavitation bubbles, we revealed that the bubble interface plays a key role in the prearrangement of drug and solvent molecules, initiating the formation of nanoparticles' seeds. The proposed mechanism can be applied to other biologically relevant molecules, suggesting that the sonochemical method can be used for the controlled formation of their nanoparticles. The results indicate a feasible way to tailor the surface of polymeric biomaterials via the embedment of nanoparticles, thus having the potential to be used for practical implications as drug delivery systems. [ABSTRACT FROM AUTHOR]

Background: The high burden of dementia and Alzheimer's disease (AD) increases substantially as disease progresses. Characterizing early patterns of health care utilization among patients who develop cognitive impairment may deepen our understanding of early disease trajectory and potentially facilitate timely diagnosis and management. Objective: Describe clinical characteristics, healthcare utilization, and costs in early-stage dementia by disease severity and amyloid-β status before enrollment in an observational study (GERAS-US). Methods: Consented patients' GERAS-US data were linked to available five-years of Medicare claims history before GERAS-US enrollment. Clinical characteristics, comorbidity, and pre-/post-diagnosis healthcare use and costs were assessed. Continuous and categorical variables were compared between severity and amyloid-status cohorts using t-test and Chi-square statistics; linear regression models were used to compare cost and utilization measures after adjusting for differences in patients' observation time. Relative likelihood of observed diagnoses, comorbidity, and prescription drug use among cohorts were presented as OR and 90% confidence interval (CI). Results: Of 174 patients clinically diagnosed with early dementia (mild cognitive impairment (MCI): 101; mild dementia (MILD): 73), 55% were amyloid-positive. Memory loss was more likely in MILD versus MCI (OR:1.85, 90% CI 1.10–3.09) and in amyloid-positive versus amyloid-negative cohorts (OR:1.98, 90% CI 1.19–3.29). Mean annual healthcare costs after cognitive impairment/dementia diagnosis were significantly higher for MILD versus MCI ($1191 versus $712, p = 0.067) and amyloid-negative versus amyloid-positive ($1281 versus $701, p = 0.034). Diabetes was more prevalent in MILD and amyloid-negative cohorts. Conclusion: Comorbidity and economic burden increased in earliest stages of MCI and MILD and were higher in patients who were amyloid-negative. [ABSTRACT FROM AUTHOR]

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W artykule dokonano charakterystyki wybranych problemów badań wizualnych luf artyleryjskich, które stanowią źródło podstawowych informacji niezbędnych dla podjęcia decyzji dotyczących badanych luf artyleryjskich lub decyzji diagnostycznych (opinia techniczna), związanych z ich dalszą eksploatacją. Badania wizualne należą do grupy badań nieniszczących pozwalających na szybkie, dokładne i jednoznaczne określenie stanu technicznego wewnętrznych przestrzeni luf armat artyleryjskich. Zaprezentowano tez przykład rozwiązań firmy Olympus współpracującej z wojskiem, w których oferowane rozwiązania powstają w oparciu o najnowsze rozwiązania technologiczne i spełniające wysokie wymagania wojskowe. Badania diagnostyczne zakończone sporządzaniem ekspertyzy i opinii technicznej w oparciu o badania wizualne luf artyleryjskich zajmują istotną pozycję w procesie bezpieczeństwa eksploatacji. Technical expertise and opinion based on visual testing artillery barrels Abstract The article presents the characteristics of selected problems of visual testing artillery barrels, which are a source of basic information necessary to make decisions regarding the respondents barrels of artillery or diagnostic decisions (technical opinion) associated with their further exploitation. Visual Testing belong to the group of NDT (Non-Destructive Testing) enabling fast, accurate and unambiguous definition of the technical condition of the interior spaces artillery cannon barrels. Also presents example solutions Olympus cooperating with the army. which offered solutions are based on the latest technology and meet demanding military specifications. Investigations completed drafting expertise and technical opinion based by visual testing artillery barrels occupy an important position in the process of safety in exploitation.