A systematic literature review of human papillomavirus vaccination strategies in delivery systems within national and regional immunization programs.

The uptake of human papillomavirus (HPV) vaccine remains suboptimal despite being a part of routine vaccination within national immunization program(s). This indicates probable challenges with the implementation of HPV immunization program(s) in various countries. The objective of this systematic literature review (SLR) was to identify implementation strategies for HPV vaccination within national and regional immunization programs worldwide with an aim to provide guidance for countries targeting to increase their HPV vaccine coverage rate (VCR). A comprehensive literature search was conducted across Medline and Embase and included articles published between January 2012 and January 2022. Of the 2,549 articles retrieved, 168 met inclusion criteria and were included in the review. Strategies shown to improve HPV vaccination uptake in the reviewed literature include campaigns to increase community awareness and knowledge of HPV, health care provider trainings, integrating HPV vaccination within school settings, coordinated efforts via multi-sectoral partnerships, and vaccination reminder and recall systems. Findings may help national authorities understand key considerations for HPV vaccination when designing and implementing programs aiming to increase HPV VCR in adolescents.

The decline of tufa deposition in an alkaline fen ecosystem in East-Central Europe and its impact on biotic assemblages: Insights from monitoring and paleoecological data.

Protection and restoration of the CaCO3 depositing alkaline fens require an in-depth understanding of these unique and declining ecosystems. The present study investigates the development of the formerly heavy tufa depositing alkaline fen in East-Central Europe after CaCO3 precipitation markedly declined ca. 5400 cal yr BP. By combining palaeoecological and monitoring data, we aim to identify the limiting factors for tufa deposition and to recognise the vegetation and mollusc response to the change. Investigation of the current fen ecosystem included a botanical and malacological inventory and a monthly monitoring of the physicochemical properties of the groundwater emerging at the fen. It was also tested whether CaCO3 precipitates there. Transformations of the fen ecosystem since the mid-Holocene tufa decline were recognized by applying plant macrofossil and malacological analyses supplemented with organic matter and CaCO3 contents and the radiocarbon chronologies of the sediment cores. Although macroscopic tufa is currently not observed at the fen surface, the monitoring study revealed the microscopic calcite crystals at the glass slides during the spring and summer. A combination of cooling, gradual depletion of the Ca2+ pool, acidification of soils, and water table fluctuations was likely responsible for limiting tufa deposition in the mid-Holocene and maintaining this state during the late Holocene. Share of the calciphilous species' macrofossils (e.g. moss Tomentypnum nitens) declined following the sedimentary CaCO3 drop, whereas the contribution of species associated with high nutrient levels raised (e.g. Juncus articulatus). Inspection of the contemporary vegetation of the fen revealed that only Carex paniculata is associated with the calcium-rich substrate. The response of molluscs to the decline in tufa deposition remains unclear as mollusc shells did not preserve in CaCO3-depleted sediments, except for the youngest deposits. The present-day malacofauna consists of 21 species, including two rare and protected calciphilous species, namely Vertigo angustior and V. geyeri.

Study of the influence of hyperglycemia on the abundance of amino acids, fatty acids, and selected lipids in extracellular vesicles using TOF-SIMS.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) with the Bi3+ liquid metal ion gun was used to investigate the content of lipids and amino acids (AAs) in extracellular vesicles (EVs). We induced metabolic changes in human pancreatic ß-cells by stimulation with high glucose concentrations (35 mM) and tested the hypothesis of hyperglycemia (HG) has a detrimental effect on lipids and AAs in released EV subpopulations: ectosomes and exosomes. As a result of HG treatment, selected fatty acids (FAs) such as arachidonic, myristic and palmitic acids, changed their abundance in ectosomes and exosomes. Also, intensities of the characteristic peaks for cholesterol (m/z 95.09; 147.07; 161.11; 369.45) along with the molecular ion m/z 386.37 [C27H46O+] under HG conditions, both for ectosomes and exosomes, have changed significantly. Comparative analysis of HG EVs and normoglycemic (NG) ones showed statistically significant differences in the signal intensities of four AAs: valine (m/z 72.08 and 83.05), isoleucine (m/z 86.10), phenylalanine (m/z 120.08 and 132.05) and tyrosine (m/z 107.05 and 136.09). We confirmed that ToF-SIMS is a useful technique to study selected AAs and lipid profiles in various EV subpopulations. Our study is the first demonstration of changes in FAs and AAs in exosomes and ectosomes derived from ß-cells under the influence of HG.

Design and Optimization of a Biosensor Surface Functionalization to Effectively Capture Urinary Extracellular Vesicles.

For this study, we tested and optimized silicon surface functionalization procedures for capturing urinary extracellular vesicles (uEVs). The influence of the silane type (APTES or GOPS) and protein concentration on the efficiency of uEVs binding was investigated. Human lactadherin protein (LACT) was used to capture uEVs. We applied surface characterization techniques, including ellipsometry, atomic force microscopy, and time-of-flight secondary ion mass spectrometry, to observe changes in the biosensor surface after each functionalization step. uEVs were purified by a low-vacuum filtration method and concentrated by ultracentrifugation. The physical parameters of uEVs after the isolation procedure, such as morphology and size distribution, were determined using transmission electron microscopy and tunable resistive pulse sensing methods. We observed a gradual growth of the molecular layer after subsequent stages of modification of the silicon surface. The ToF-SIMS results showed no changes in the mean intensities for the characteristic peaks of amino acids and lipids in positive and negative polarization, in terms of the surface-modifying silane (APTES or GOPS) used. The most optimal concentration of LACT for the tested system was 25 µg/mL.

Endosialin (CD248) Expression in Fibromas and Soft-tissue Fibrosarcomas in Dogs.

BACKGROUND/AIM: Endosialin is present in human fibrosarcoma neoplastic cells. This study aimed to analyse the expression of selected cellular proteins found in fibrosarcomas and soft-tissue fibroids in dogs. MATERIALS AND METHODS: A total of 71 skin tumours obtained from dogs were used. The samples included 31 fibromas and 40 fibrosarcomas. Histopathological evaluation was performed according to World Health Organization guidelines. Immunohistochemistry was performed with anti-endosialin, Ki-67, cyclo-oxygenase 2 and vimentin antibodies and assessed using the semi-quantitative scale. RESULTS: Endosialin expression was observed in 82.5% of fibrosarcomas and in 35% of fibromas. A significant positive correlation was found between the expression of endosialin in fibrosarcoma neoplastic cells and the degree of histological malignancy and the expression of the Ki-67 and cyclo-oxygenase 2 antigen. Expression of vimentin confirmed mesenchymal origin of this tumours. CONCLUSION: The results of our research suggest that endosialin is involved in the carcinogenesis of fibrosarcoma in dogs.

Lake-stream transition zones support hotspots of freshwater ecosystem services: Evidence from a 35-year study on unionid mussels.

Securing adequate supply of high-quality water is of increasing global importance and relies in large part on ecosystem services provided by freshwater biota. Unionid mussels are important keystone species and habitat engineers that shape freshwater ecosystems through water filtration, nutrient cycling and provision of habitats; their rapid global declines result in dramatic losses of ecosystem functions. Maintenance and enhancement of the services they provide depend on the identification of their crucial habitats. Following theoretical assumptions, this study analyses the importance of lake-stream transition zones for unionid mussels, based on data collected in 1984 and 2019 from an undisturbed stream flowing through five consecutive lakes. Mussel distribution matched the distribution of host fish and was strongly influenced by lakes: densities were highest near lake outlets, reaching 290 ind. m-2 (14.7 kg m-2) in 2019, and declined with downstream distance following a negative power function. This pattern was spatially consistent and sustained over time. All six unionid species native to north-central Europe were present, but common species (Anodonta anatina, Unio pictorum, U. tumidus) contributed about 80% of individuals and were responsible for most of the ecosystem services provided by unionid mussels. Estimated 1.9 × 106 mussel individuals inhabiting 3.2 km of stream length filtered a water volume equivalent to the total stream discharge approximately 2.5 times daily. Aggregations of spent shells, up to 17 kg m-2, accumulated downstream of lakes, forming extensive shell and mussel beds, providing habitats and contributing shell hash that improved stream-bed conditions. Globally invasive Dreissena polymorpha was present at low densities and did not spread or increase in abundance, indicating a long-term biotic resistance of the natural native community. Our study underscores the importance of undisturbed lake outlets, longitudinal connectivity of riverine ecosystems, and of common mussel species in maintaining freshwater ecosystem functionality and provision of vital services.

Using a lactadherin-immobilized silicon surface for capturing and monitoring plasma microvesicles as a foundation for diagnostic device development.

Microvesicles (MVs) are found in several types of body fluids and are promising disease biomarkers and therapeutic targets. This study aimed to develop a novel biofunctionalized surface for binding plasma microvesicles (PMVs) based on a lab-on-a-chip (LOC) approach. A new lactadherin (LACT)-functionalized surface was prepared and examined for monitoring PMVs. Moreover, two different strategies of LACT immobilization on a silicon surface were applied to compare different LACT orientations. A higher PMV to LACT binding efficiency was observed for LACT bonded to an αvß3 integrin-functionalized surface compared with that for LACT directly bonded to a glutaraldehyde-modified surface. Effective binding of PMVs and its components for both LACT immobilization strategies was confirmed using spectral ellipsometry and time-of-flight secondary ion mass spectrometry methods. The proposed PMV capturing system can be used as a foundation to design novel point-of-care (POC) diagnostic devices to detect and characterize PMVs in clinical samples. Graphical Abstract.

ToF-SIMS spectrometry to observe fatty acid profiles of breast tissues in broiler chicken subjected to varied vegetable oil diet.

This study is aimed to observe changes in fatty acid profiles by time of flight secondary ion mass spectrometry (ToF-SIMS) in breast muscle tissues of broilers. Four different groups were identified. The source of fat in group I was soy oil (rich in linoleic acid, ω-6), group II received linseed oil (ω-3), and the third group was fed a mixture of the two mentioned oils. Broilers in the control group were fed with beef tallow, used in mass commercial production. The results reveal that the use of vegetable oils in animal nutrition determines the lipid profile of fatty acids. ToF-SIMS measurements showed that the lipid profile of muscle fibers and intramuscular fat reflect the composition of fats used as feed additives. In both structures, the ratio of ω-6/ω-3 fatty acids, which is most favorable for human health, was found in the groups in which a mixture of vegetable oils and a supplement of linseed oil were used.

Circulating Immune Complexes and Heat Shock Protein 70 in the Sera of Patients with Sudden Sensorineural Hearing Loss.

OBJECTIVES: The aim of this paper is to analyze and assess the usefulness of heat shock protein 70 (Hsp70) and circulating immune complexes (CIC) in patients with sudden sensorineural hearing loss (SSHL) in a tertiary care hospital in a research university (2014-2017). MATERIALS AND METHODS: Patients were interviewed about the history of diseases; underwent an ear, nose, and throat (ENT) examination; a hearing test; and were analyzed for the presence of CIC and Hsp70 protein. A simple dot blot method was designed for the purpose of identification of Hsp70 bound to CIC and free Hsp70. RESULTS: In 59.4% of patients with idiopathic SSHL, elevated levels of immune complexes were observed. Compared with healthy subjects, a significant difference was noted (p=0.00016). Positive reactions to the presence of free Hsp70 protein were noted in the sera of 48.4% of patients. In the control group, free Hsp70 was observed in 8% of patients (p=0.0000034). Hsp70 bound to CIC was detected in the sera of 62.5% of patients; and in healthy cases, in 12% (p<0.0001). CONCLUSION: In the sera of persons with SSHL, there are elevated levels of CIC and Hsp70. After the application of the innovative method for determining the occurrence of Hsp70 bound to CIC, it was stated that its presence is greater than that of free Hsp70, commonly detected by means of the Western-blot method. The dot blot method applied in the present study increases the Hsp70 identification and by the same token increases the probability of detection of autoimmunological background of SSHL.

Chance of reimbursement for ADD-ON therapies in Poland and in the world - review of the reimbursement recommendations

INTRODUCTION: Oncology drugs combined with standard therapies (so-called add-on therapies, e.g. bevacizumab, palbociclib) often receive negative recommendations regarding the legitimacy of public financing, issued by government agencies responsible for their assessment, i.e. health technology assessment agencies. The aim of the study was to estimate the scale of the problem related to the reimbursement of add-on therapies used in the treatment of breast and genitourinary cancers in Poland and in the world. MATERIAL AND METHODS: A multimodal approach was used to select add-on therapies. The reimbursement routes were analysed in 8 reference countries (Poland, Canada, England, Wales, France, Scotland, Australia, New Zealand). Based on a systematic search, data for breast and urogenital cancers were included. RESULTS: A total of 68 reimbursement documents for add-on therapies were identified. The analysis showed that in Poland, 20% of innovative schemes including add-on therapies should be reimbursed, while in the world the percentage of positive recommendations reaches 56%. It was observed that globally (including data for Poland) the chance for a favorable reimbursement recommendation for add-on therapies is 53%, with 29% being positive recommendations with limitations. In Poland, the majority of negative recommendations concern genitourinary cancers in comparison to breast cancer (83% vs 75%). CONCLUSIONS: Poland is at the head of the countries in terms of the number of negative reimbursement recommendations. Bearing in mind the world's need of modifying the criteria for the evaluation of oncological therapies in the context of the possibility of their reimbursement, one should expect a change in the approach to the assessment of the legitimacy of financing innovative add-on therapies in Poland.

Study of cholesterol and vitamin E levels in broiler meat from different feeding regimens by TOF-SIMS.

The quality of chicken meat, which is one of the most widely consumed meats in the world, has been the subject of research and studies for many years. There are several ways to improve the quality of this type of meat, including changing the concentrations of individual molecular components. Such important components of meat are inter alia, cholesterol, vitamin E, and some fatty acids such as ω-3 and ω-6. Manipulation of ingredient levels may be achieved by enriching chicken feed with elements of different types such as vegetable oils, garlic, or selenium. Thus far, various biochemical and biophysical methods have been used to study quality of different meat types, especially broiler meat. Here, the authors demonstrate the use of high-resolution time-of-flight secondary ion mass spectrometry (TOF-SIMS) mass spectrometry to assess how variations in animal nutrition affect concentrations of specific lipids in the meat, such as cholesterol and vitamin E. In the presented experiment, there were four different dietary treatments. Feed for animals in the first group was supplemented with soy oil in 50%, the second group's feed was supplemented with linseed oil in 50%, a combination of these two oils in the proportion of 44%:56% was used for the third group, and in the reference group, animals were fed with beef tallow. From each group, four individuals were selected for further analysis. Positive and negative ion mass spectra were generated from the pectoralis superficialis muscle tissue of the left carcass side of each one animal. Using TOF-SIMS with a bismuth cluster ion source (Bi3 (+)), and based on characteristic peaks for cholesterol in the positive mode and vitamin E in the negative mode, the authors have illustrated the relationship of these lipids levels to the various feeding regimens. Simultaneously, the authors characterized the varying dependences on the concentrations of measured lipids in fat and muscle fibers. The cholesterol concentration in muscle fibers was the lowest in the group fed with soybean oil and the highest in reference group IV (tallow feed). In the fatty region, the highest level of cholesterol was found in the third group. The highest concentrations of vitamin E were found in the fibers of the first group and the fat region of the second group. The obtained results show that SIMS imaging is a useful approach for assessing changes in lipid concentrations in the meat tissue from animals on different diets and provides a foundation for future research.

Relevance of the poly(ethylene glycol) linkers in peptide surfaces for proteases assays.

Poly(ethylene glycol)s (PEGs) with different lengths were used as linkers during the preparation of peptide surfaces for protease detection. In the first approach, the PEG monolayers were prepared using a "grafting to" method on 3-aminopropyltrietoxysilane (APTES)-modified silicon wafers. Protected peptides with a fluorescent marker were synthesized by Fmoc solid phase synthesis. The protected peptide structures enabled their site-specific immobilization onto the PEG surfaces. Alternatively, the PEG-peptide surface was obtained by immobilizing a PEG-peptide conjugate directly onto the modified silicon wafer. The surfaces (composition, grafting density, hydrophilicity, and roughness) were characterized by time-of-flight-secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS), contact angle (CA), and atomic force microscopy (AFM). Introducing the PEG linker between the peptide and surface increased their resistance toward nonspecific protein adsorption. The peptide surfaces were examined as analytical platforms to study the action of trypsin as a representative protease. The products of the enzymatic hydrolysis were analyzed by fluorescence spectroscopy, electrospray ionization-mass spectrometry (ESI-MS), and ToF-SIMS. Conclusions about the optimal length of the PEG linker for the analytical application of PEG-peptide surfaces were drawn. This work demonstrates an effective synthetic procedure to obtain PEG-peptide surfaces as attractive platforms for the development of peptide microarrays.