Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review.

Oral cancer is a prevalent global health issue, with significant morbidity and mortality rates. Despite available preventive measures, it remains one of the most common cancers, emphasising the need for improved diagnostic and prognostic tools. This review focuses on oral potentially malignant disorders (OPMDs), precursors to oral cancer, specifically emphasising oral epithelial dysplasia (OED). The World Health Organisation (WHO) provides a three-tier grading system for OED, and recent updates have expanded the criteria to enhance diagnostic precision. In the prognostic evaluation of OED, histological grading is presently regarded as the gold standard; however, its subjectivity and unreliability in anticipating malignant transformation or recurrence pose notable limitations. The primary objective is to investigate whether specific immunohistochemical biomarkers can enhance OED grading assessment according to the WHO classification. Biomarkers exhibit significant potential for comprehensive cancer risk evaluation, early detection, diagnosis, prognosis, and treatment optimisation. Technological advancements, including sequencing and nanotechnology, have expanded detection capabilities. Some analysed biomarkers are most frequently chosen, such as p53, Ki-67, cadherins/catenins, and other proteins used to differentiate OED grades. However, further research is needed to confirm these findings and discover new potential biomarkers for precise dysplasia grading and minimally invasive assessment of the risk of malignant transformation.

The Role of the Microbiome in the Pathogenesis and Treatment of Asthma.

The role of the microbiome in the pathogenesis and treatment of asthma is significant. The purpose of this article is to show the interplay between asthma and the microbiome, and main areas that require further research are also highlighted. The literature search was conducted using the PubMed database. After a screening process of studies published before May 2023, a total of 128 articles were selected in our paper. The pre-treatment bronchial microbiome in asthmatic patients plays a role in their responsiveness to treatment. Gut microbiota and its dysbiosis can contribute to immune system modulation and the development of asthma. The association between the microbiome and asthma is complex. Further research is necessary to clarify which factors might moderate that relationship. An appropriate gut microbiome and its intestinal metabolites are a protective factor for asthma development. Prebiotics and certain dietary strategies may have a prophylactic or therapeutic effect, but more research is needed to establish final conclusions. Although the evidence regarding probiotics is ambiguous, and most meta-analyses do not support the use of probiotic intake to reduce asthma, several of the most recent studies have provided promising effects. Further studies should focus on the investigation of specific strains and the examination of their mechanistic and genetic aspects.

Extracellular Vesicles as Drug Transporters.

Extracellular vesicles (EVs) are lipid bilayer-delimited particles. According to their size and synthesis pathway, EVs can be classified into exosomes, ectosomes (microvesicles), and apoptotic bodies. Extracellular vesicles are of great interest to the scientific community due to their role in cell-to-cell communication and their drug-carrying abilities. The study aims to show opportunities for the application of EVs as drug transporters by considering techniques applicable for loading EVs, current limitations, and the uniqueness of this idea compared to other drug transporters. In addition, EVs have therapeutic potential in anticancer therapy (especially in glioblastoma, pancreatic cancer, and breast cancer).

In Vitro and In Vivo Biocompatibility of Natural and Synthetic Pseudomonas aeruginosa Pyomelanin for Potential Biomedical Applications.

Bacteria are the source of many bioactive compounds, including polymers with various physiological functions and the potential for medical applications. Pyomelanin from Pseudomonas aeruginosa, a nonfermenting Gram-negative bacterium, is a black-brown negatively charged extracellular polymer of homogentisic acid produced during L-tyrosine catabolism. Due to its chemical properties and the presence of active functional groups, pyomelanin is a candidate for the development of new antioxidant, antimicrobial and immunomodulatory formulations. This work aimed to obtain bacterial water-soluble (Pyosol), water-insoluble (Pyoinsol) and synthetic (sPyo) pyomelanin variants and characterize their chemical structure, thermosensitivity and biosafety in vitro and in vivo (Galleria mallonella). FTIR analysis showed that aromatic ring connections in the polymer chains were dominant in Pyosol and sPyo, whereas Pyoinsol had fewer Car-Car links between rings. The differences in chemical structure influence the solubility of various forms of pyomelanins, their thermal stability and biological activity. Pyosol and Pyoinsol showed higher biological safety than sPyo. The obtained results qualify Pyosol and Pyoinsol for evaluation of their antimicrobial, immunomodulatory and proregenerative activities.

Enhanced Antifungal Activity of Amphotericin B Bound to Albumin: A "Trojan Horse" Effect of the Protein.

Amphotericin B (AmB) is a life-saving and widely used antifungal antibiotic, but its therapeutic applicability is limited due to severe side effects. Here, we report that the formulation of the drug based on a complex with albumin (BSA) is highly effective against Candida albicans at relatively low concentrations, which implies lower toxicity to patients. This was also concluded based on the comparison with antifungal activities of other popular commercial formulations of the drug, such as Fungizone and AmBisome. Several molecular spectroscopy and imaging techniques, e.g., fluorescence lifetime imaging microscopy (FLIM), were applied to understand the phenomenon of enhanced antifungal activity of the AmB-BSA complex. The results show that the drug molecules bound to the protein remain mostly monomeric and are most likely bound in the pocket responsible for the capture of small molecules by this transport protein. The results of molecular imaging of single complex particles indicate that in most cases, the antibiotic-protein stoichiometry is 1:1. All of the analyses of the AmB-BSA system exclude the presence of the antibiotic aggregates potentially toxic to patients. Cell imaging shows that BSA-bound AmB molecules can readily bind to fungal cell membranes, unlike drug molecules present in the aqueous phase, which are effectively retained by the cell wall barrier. The advantages and prospects of pharmacological use of AmB complexed with proteins are discussed.

Is There a Correlation between Dental Occlusion, Postural Stability and Selected Gait Parameters in Adults?

Background: There is still an ongoing debate about the role of the craniomandibular system, including occlusal conditions, on postural stability. This study aims to assess the role of antero-posterior malocclusion on postural control and plantar pressure distribution during standing and walking. Methods: 90 healthy volunteers (aged 19 to 35) were qualified for the study. The subjects were assigned to three groups, depending on the occlusion type. Each group (Angle Class I, II and III) consisted of 30 people. The research procedure included a clinical occlusal assessment performed by a dentist. Postural control measurements were carried out using a force platform by measuring plantar pressure distribution during standing (six trials with and without visual control) and walking test conditions. Results: The tendency to shift the CoP forward is demonstrated by Angle Class II subjects and backwards by Class I and III subjects (p < 0.001). Individuals with a malocclusion demonstrated significantly higher selected stabilographic parameters while standing on both feet (with eyes open and closed) and during the single-leg test with eyes open (p < 0.05). The analysis of the dynamic test results showed no significant correlations between Angle Classes and the selected gait parameters. Conclusions: Analyses conducted among individuals with malocclusions showed the impact of occlusion on static postural stability. In order to diagnose and effectively treat malocclusion, a multidisciplinary approach with the participation of dentists and physiotherapy specialists is necessary, with the use of stabilometric and kinematic posture assessments.

Reactions of 3-Hydroxy-2-phenyl-1H-benzo[e]isoindol-1-one: A Route to 3-Hydroxy-/3-anilinobenzo[e]indan-1-ones and Benzo[f]phthalazin-1(2H)-ones.

New hydroxy- and anilinoindanone derivatives 3 and 4 were synthesized starting from 3-hydroxybenzo[e]isoindolinone 1 via the addition of alkyllithium (s-BuLi, n-BuLi, MeLi or i-PrLi) to the carbonyl group, followed by lactam ring opening and, finally, an intramolecular cyclization leading to target compounds. The same starting material was used for the preparation of the new benzo[f]phthalazinone derivatives 12-16 through multi-step reactions. The target derivative 16 was obtained from the corresponding bromolactam 15 by the Buchwald-Hartwig amination. Structures of the obtained compounds were confirmed by the NMR spectra.

Amelanotic Uveal Melanomas Evaluated by Indirect Ophthalmoscopy Reveal Better Long-Term Prognosis Than Pigmented Primary Tumours-A Single Centre Experience.

(1) Background: There is a constant search for new prognostic factors that would allow us to accurately determine the prognosis, select the type of treatment, and monitor the patient diagnosed with uveal melanoma in a minimally invasive and easily accessible way. Therefore, we decided to evaluate the prognostic role of its pigmentation in a clinical assessment. (2) Methods: The pigmentation of 154 uveal melanomas was assessed by indirect ophthalmoscopy. Two groups of tumours were identified: amelanotic and pigmented. The statistical relationships between these two groups and clinical, pathological parameters and the long-term survival rate were analyzed. (3) Results: There were 16.9% amelanotic tumours among all and they occurred in younger patients (p = 0.022). In pigmented melanomas, unfavourable prognostic features such as: epithelioid cells (p = 0.0013), extrascleral extension (p = 0.027), macronucleoli (p = 0.0065), and the absence of BAP1 expression (p = 0.029) were statistically more frequently observed. Kaplan−Meier analysis demonstrated significantly better overall (p = 0.017) and disease-free (p < 0.001) survival rates for patients with amelanotic tumours. However, this relationship was statistically significant for lower stage tumours (AJCC stage II), and was not present in larger and more advanced stages (AJCC stage III). (4) Conclusions: The results obtained suggested that the presence of pigmentation in uveal melanoma by indirect ophthalmoscopy was associated with a worse prognosis, compared to amelanotic lesions. These findings could be useful in the choice of therapeutic and follow-up options in the future.

A 63-Year-Old Man with a Diagnosis of Re-Infection with SARS-CoV-2 Nine Weeks After an Initial Hospital Admission with COVID-19 Pneumonia.

BACKGROUND This report describes a 63-year-old Polish man presenting with COVID-19 (Coronavirus Disease 2019) pneumonia in early 2020, before vaccines to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were available. Nine weeks following recovery from the initial infection, he tested positive again for SARS-CoV-2. CASE REPORT Man, age 63, was admitted to the Military Institute of Medicine on March 12, 2020, with body temperature 40°C, a cough, and breathlessness. On March 12, 2020, SARS-CoV-2 RNA was found in a nasopharynx smear. A chest X-ray (RTG) showed discrete areas of interstitial densities. On June 13, 2020, after 32 days of hospitalization and 2 negative real-time polymerase chain rection (RT-PCR) test results, patient was released home in good general condition. On July 23, 2020 he reported to the emergency room with fever of 39°C and general weakness. A nasopharynx smear confirmed SARS-CoV-2 infection. On admission, the patient was in moderately good condition with auscultatory changes typical for pneumonia on both sides of the chest. On the seventh day of hospitalization, the patient was transported to the Intensive Care Unit (ICU) due to drastic deterioration in respiratory function. Respiratory support with non-invasive high-flow oxygen therapy (Opti-Flow) was used. On August 20, 2020, after negative RT-PCR test results, he was discharged in good general condition. CONCLUSIONS This case of COVID-19 pneumonia presented early in the COVID-19 pandemic of 2020, and the laboratory diagnosis of the initial and subsequent SARS-CoV-2 infection relied on the laboratory methods available at that time. However, several cases of repeat SARS-CoV-2 infection have been described before the development of vaccines in late 2020.

Biomarker-Based Determination of Equiseti herba Contamination by Equisetum palustre Using HPLC-MS/MS.

Equiseti herba has been traditionally indicated in bacterial diseases of the efferent urinary tract or bad healing wounds in many regions worldwide. Most of the plant material used for medical purposes comes from collections of wild growing plants. The European Pharmacopoeia requires that Equiseti herba should consist of a minimum of 95% Equisetum arvense and a maximum of 5% foreign ingredients. This includes Equisetum palustre, which is known for its potentially toxic alkaloid palustrine. However, both Equisetum species are quite common, look morphologically very similar, and share similar habitats, hence, are therefore often confused. Recently, several structurally related Equisetum alkaloids have been identified in E. palustre but not in E. arvense. We have established a hydrophilic interaction liquid chromatography HPLC-ESI-MS/MS method for the detection of these E. palustre-specific Equisetum alkaloids in order to quantify the contamination of Equiseti herba (E. arvense) by E. palustre plant material. In a second, independent approach, the results of the HPLC-MS/MS analysis were confirmed by scanning electron microscopy, looking for the species-specific characteristics of the stoma apparatus of E. palustre. Thirty-four Equiseti herba products obtained from different pharmacies, drug stores, supermarkets, and web stores were analyzed. The majority of the products (26 out of 34) were Equisetum alkaloid positive, with contents ranging from 0.29 - 21.7 mg of Equisetum alkaloids/kg (d. w.). In addition, the transfer of Equisetum alkaloids into tea infusions was investigated, demonstrating a 42 to 60% transfer rate for cold and hot water extraction of Equisetum alkaloid-contaminated Equiseti herba, respectively.

Salivary Metabolomics for Systemic Cancer Diagnosis: A Systematic Review.

Cancers are the leading cause of death worldwide. The most common cancers include breast, lung, and colorectum. Salivary metabolome profiling is a novel non-invasive method in oncological diagnosis. This systematic review was designed to answer the question "Are salivary metabolites reliable for the diagnosis of systemic cancers?". Following the inclusion and exclusion criteria, nineteen studies were included (according to PRISMA statement guidelines). Changes in salivary metabolome were most commonly determined in patients with breast cancer, gastrointestinal cancers, and lung cancer. Most studies involved unstimulated whole saliva as the diagnostic material, evaluated by different spectroscopic methods. Among the found saliva metabolites, the alterations in the metabolic pathways of amino acids and polyamines were most frequently observed, which showed significant predictive values in oncological diagnostics. The most frequently encountered risks of bias were the absence of data regarding blinding, sample size justification, and randomisation. In conclusion, salivary metabolites seem to be potentially reliable for detecting the most common systemic cancers. However, further research is desirable to confirm these outcomes and to detect new potential metabolic biomarkers in saliva.

Lipidomic response of the entomopathogenic fungus Beauveria bassiana to pyrethroids.

Pyrethroids are chemical insecticides that are widely used to control pests. Entomopathogenic fungi are considered environmentally safe alternatives to these compounds. Pyrethroids and entomopathogenic fungi not only co-exist in the environment but can also be applied together in pest control. They are often found in contact with each other, and thus, it seems important to understand their interactions at the cellular level. In this study, we analyzed whether pyrethroids could influence the phospholipid profile of Beauveria bassiana and whether membrane changes are one of the mechanisms by which these fungi adapt to unfavorable environmental conditions. The results of our study revealed that pyrethroids changed the phospholipid profile and increased the cell membrane permeability of B. bassiana, which enabled them to enter and accumulate within the fungal cells, resulting in oxidative stress. Pyrethroids influenced the amount of neutral lipids, caused a decrease in sodium content, and also temporarily lowered the level of the secondary metabolite oosporein in the studied fungi. These findings indicate that the effect of pyrethroids on entomopathogenic fungi may be more complex than originally thought and that lipidomic studies can aid in fully understanding the influence of these chemicals on the mentioned group of fungi.

Choroidal metastases of thymic carcinoma in ultrasonographic imaging and optical coherence tomography.

Not required for Clinical Vignette.

The Effectiveness of the Blended Learning in Conservative Dentistry with Endodontics on the Basis of the Survey among 4th-Year Students during the COVID-19 Pandemic.

The COVID-19 pandemic has undoubtedly affected education at all levels, including medical and dental education. Our study aimed to assess the effectiveness of the blended learning in conservative dentistry with endodontics. The students had theoretical classes in a remote form (using the e-learning portal and Teams communicator) and practical classes with the participation of patients in the appropriate sanitary regime. The author's survey was conducted among fourth-year dental students. The online questionnaire consisted of 5 parts: self-evaluation, evaluation of theoretical e-learning classes, evaluation of practical clinical classes, evaluation of safety, and evaluation of performed blended learning. The majority of respondents declared that their learning effectiveness increased during the pandemic. Most surveyed students preferred remote learning in asynchronous form (e-learning portals) to synchronous form (virtual meetings in real-time). All respondents described the provided personal protective equipment as sufficient or even as excessive. Our students were very satisfied with the proposed blended-learning model and would like to continue it even after the pandemic has ended. Among the advantages, they particularly mentioned the increase in efficiency and the individualised pace of learning, while the disadvantage was the limitation of social contacts. The appropriate use of modern technology can effectively revolutionise dental education.

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity.

Amino- and polyaminophthalazinones were synthesized by the palladium-catalyzed amination (alkyl- and arylamines, polyamines) of 4-bromophthalazinones in good yields. The coordinating properties of selected aminophthalazinones towards Cu(II) ions were investigated and the participation of the nitrogen atoms in the complexation of the metal ion was shown. A biological screening of the potential cytotoxicity of selected synthesized compounds on HT-29 and PC-3 cell lines, as well as on the L-929 cell line, proved that some amino derivatives of phthalazinone show interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays are reported.

Acetamiprid Affects Destruxins Production but Its Accumulation in Metarhizium sp. Spores Increases Infection Ability of Fungi.

Metarhizium sp. are entomopathogenic fungi that inhabit the soil environment. Together, they act as natural pest control factors. In the natural environment, they come into contact with various anthropogenic pollutants, and sometimes, they are used together and interchangeably with chemical insecticides (e.g., neonicotinoids) for pest control. In most cases, the compatibility of entomopathogens with insecticides has been determined; however, the influence of these compounds on the metabolism of entomopathogenic fungi has not yet been studied. Secondary metabolites are very important factors that influence the fitness of the producers, playing important roles in the ability of these pathogens to successfully parasitize insects. In this study, for the first time, we focus on whether the insecticide present in the fungal growth environment affects secondary metabolism in fungi. The research revealed that acetamiprid at concentrations from 5 to 50 mg L-1 did not inhibit the growth of all tested Metarhizium sp.; however, it reduced the level of 19 produced destruxins in direct proportion to the dosage used. Furthermore, it was shown that acetamiprid accumulates not only in plant or animal tissues, but also in fungal cells. Despite the negative impact of acetamiprid on secondary metabolism, it was proofed to accumulate in Metarhizium spores, which appeared to have a stronger infectious potential against mealworm Tenebrio molitor, in comparison to the insecticide or the biological agent alone.

Correction to: Performance of a feature-based algorithm for 3D-3D registration of CT angiography to cone-beam CT for endovascular repair of complex abdominal aortic aneurysms.

In the original version of this article [1], published on 8 November 2018, there was an error in the name of the 2nd author.

4-n-nonylphenol degradation by the genus Metarhizium with cytochrome P450 involvement.

In this study, the ability of 4-n-nonylphenol (4-n-NP) elimination by fungal species belonging to the genus Metarhizium was investigated. The occurrence of 35 metabolites from 4-n-NP degradation was confirmed. For the first time, based on the obtained results, the 4-n-NP biodegradation pathway distinctive for the genus Metarhizium was proposed. Principal Component Analysis (PCA) indicated that despite the similar elimination pathway in all the examined Metarhizium species, there are significant differences in the kinetics of degradation of 4-n-NP. Oxidation of the terminal methyl group of the aliphatic chain leading to the formation of carboxylic acids coupled with the removal of terminal carbon is characteristic of M. robertsii and M. guizhouense, whereas metabolites with a hydroxyl group in the distal part of the nonyl chain distinguish M. lepidiotae and M. majus. Additionally, this study verified the participation of cytochrome P450 in the elimination of the xenobiotic by Metarhizium as experimentally proven for M. robertsii.

Performance of a feature-based algorithm for 3D-3D registration of CT angiography to cone-beam CT for endovascular repair of complex abdominal aortic aneurysms.

BACKGROUND: A crucial step in image fusion for intraoperative guidance during endovascular procedures is the registration of preoperative computed tomography angiography (CTA) with intraoperative Cone Beam CT (CBCT). Automatic tools for image registration facilitate the 3D image guidance workflow. However their performance is not always satisfactory. The aim of this study is to assess the accuracy of a new fully automatic, feature-based algorithm for 3D3D registration of CTA to CBCT. METHODS: The feature-based algorithm was tested on clinical image datasets from 14 patients undergoing complex endovascular aortic repair. Deviations in Euclidian distances between vascular as well as bony landmarks were measured and compared to an intensity-based, normalized mutual information algorithm. RESULTS: The results for the feature-based algorithm showed that the median 3D registration error between the anatomical landmarks of CBCT and CT images was less than 3 mm. The feature-based algorithm showed significantly better accuracy compared to the intensity-based algorithm (p < 0.001). CONCLUSION: A feature-based algorithm for 3D image registration is presented.

Impact of Window Computed Tomography (CT) Parameters on Measurement of Inflammatory Changes in Paranasal Sinuses.

BACKGROUND: In accordance with the European guidelines on rhinosinusitis and nasal polyps (EPOS 2012), CT is used as the main imaging modality for the assessment intensity of inflammatory lesions.The aim of this study was to measure the differences in the assessment of inflammatory changes in the paranasal sinuses due to different parameters of width (W) and length (L) of the CT window. MATERIAL/METHODS: A retrospective analysis included 44 CT scans of the paranasal sinuses that were performed in adults. All studies were characterized by the presence of inflammatory changes in at least one of the sinuses.Measurements of the same inflammatory lesions were performed sequentially with different CT windows. The results were statistically analyzed. RESULTS: A statistically significant difference was observed between the average measurements that were performed with the use CT windows dedicated for the sinuses and head. A downward trend in the measured values and a shift towards soft tissue values was observed with decreasing window parameters. CONCLUSIONS: A major cause of inaccurate examinations of pathological changes in the paranasal sinuses may be due to selection of unsuitable CT windows. Therefore, in order to avoid missing inflammatory lesions in the paranasal sinuses, it is reasonable to use CT windows dedicated for the sinuses or bones.