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Background The thorough understanding of the physiological and pathological processes mediated by extracellular vesicles (EVs) is challenged by purification methods which are cumbersome, not reproducible, or insufficient to yield homogeneous material. Chromatography based on both ion-exchange and immune-capture can represent an effective method to improve EV purification and successive analysis. Methods Cell culture supernatant was used as a model sample for assessing the capacity of anion-exchange chromatography to separate distinct EV fractions and to isolate nanobodies by direct panning on whole EVs to recover binders specific for the native conformation of EV-surface epitopes and suitable to develop EV immune-capture reagents. Results Anion-exchange chromatography of cell culture supernatant separated distinct protein-containing fractions and all of them were positive for CD9, a biomarker associated to some EVs. This suggested the existence of several EV fractions but did not help in separating EVs from other contaminants. We further isolated several nanobodies instrumental for implementing immune-affinity protocols. These were able to immobilize EVs from both cell culture supernatant and biological samples, to be used in ELISA, flow-cytometry, and immune-purification. Conclusions Here we report the first successful isolation of anti-EV nanobodies for the use in immunoaffinity-based EV capture by panning a phage library directly on partially purified EVs. This achievement paves the way for the application of direct EV panning for the discovery of novel antibody-vesicle surface biomarker pairs and represents the preliminary requirement for the development of selective immune-capture that, in combination with anion-exchange chromatography, can simplify the systematic stratification of EV sub-populations and their individual characterization.

Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of therapy, pancytopenia was observed. Other causes were excluded through extensive diagnostic evaluation, including immunological tests, viral serologies, bone marrow aspiration, and peripheral blood smear. The patient’s clinical condition significantly improved following the discontinuation of ceftriaxone and the administration of granulocyte colony-stimulating factor (G-CSF). Bone marrow findings revealed hypocellularity without malignant infiltration, and peripheral smear showed no dysplasia, blasts, or hemolysis. Conclusions: This case demonstrates that ceftriaxone, although widely regarded as a safe antibiotic, can induce rare but serious hematologic complications such as pancytopenia. A high index of suspicion is required when patients on antibiotic therapy develop unexplained cytopenias. Detailed medication history, exclusion of other causes, and prompt discontinuation of the suspected drug are essential. The patient’s favorable outcome supports the likelihood of an idiosyncratic, immune-mediated mechanism. Future research should explore pharmacogenomic screening in patients at increased risk, particularly involving HLA variants.

Inaccurate estimation of average dielectric properties can have a tangible impact on microwave radar-based breast images. Despite this, recent patient imaging studies have used a fixed estimate although this is known to vary from patient to patient. Parameter search algorithms are a promising technique for estimating the average dielectric properties from the reconstructed microwave images themselves without additional hardware. In this work, qualities of accurately reconstructed images are identified from point spread functions. As the qualities of accurately reconstructed microwave images are similar to the qualities of focused microscopic and photographic images, this work proposes the use of focal quality metrics for average dielectric property estimation. The robustness of the parameter search is evaluated using experimental dielectrically heterogeneous phantoms on the three-dimensional volumetric image. Based on a very broad initial estimate of the average dielectric properties, this paper shows how these metrics can be used as suitable fitness functions in parameter search algorithms to reconstruct clear and focused microwave radar images.

Considerable exploration has been done in recent years to exploit the reported inherent dielectric contrast between healthy and malignant tissues for a range of medical applications. In particular, microwave technologies have been investigated towards new diagnostic medical tools. To assess the performance and detection capabilities of such systems, tissue-mimicking phantoms are designed for controlled laboratory experiments. We here report phantoms developed to dielectrically represent malign skin lesions such as liposarcoma and nonsyndromic multiple basal cell carcinoma. Further, in order to provide a range of anatomically realistic scenarios, and provide meaningful comparison between different phantoms, cancer-mimicking lesions are inserted into two different types of skin phantoms with varying tumor–skin geometries. These configurations were measured with a microwave dielectric probe (0.5–26.5 GHz), yielding insight into factors that could affect the performance of diagnostic and detection tools.

Studies have suggested that arginine vasopressin (AVP) and its surrogate marker copeptin increase during exercise, independently of serum sodium and/or osmolality. In extreme cases, this can lead to runners-induced hyponatremia. Interleukin-1 (IL-1) increases during exercise and induces AVP in animal models. We here therefore investigate whether copeptin (a surrogate marker for AVP) increases upon exercise in young and healthy males, and whether this increase is regulated by IL-1. In a randomized, placebo-controlled, double-blind, crossover trial in 17 healthy male volunteers, the effect of the IL-1 receptor antagonist anakinra on exercise-induced copeptin was compared with placebo. Participants exercised for one hour at 75% of VO2max and were not allowed to drink/eat 6 hours before and during the study. Participants received either 100 mg of anakinra or placebo 1h before exercise. Blood was drawn at certain time intervals. In both groups, copeptin levels were induced by 2.5-fold upon exercise (p<0.001), from 4.5-10.6 pmol/l in the placebo, and 4.3-11.3 pmol/l in the anakinra group, (p = 0.38). One hour after exercise, copeptin levels dropped to 7.7 and 7.9 pmol/l in the placebo and anakinra group, respectively (p = 0.58). The increase of copeptin levels was not explained by sodium concentrations. Exercise induces a continuous rise of plasma copeptin levels in healthy male volunteers independently of sodium levels and fluid intake. This increase is not regulated by the IL-1 pathway.

The emergence of drug‐resistant viruses and novel strains necessitates the rapid development of novel antiviral therapies. This need was particularly demanding during the COVID‐19 pandemic. While de novo drug development is a time‐consuming process, repurposing existing approved medications offers a more expedient approach. In our prior in silico screening of the DrugBank database, fidaxomicin emerged as a potential SARS‐CoV‐2 papain‐like protease inhibitor. This study extends those findings by investigating fidaxomicin‘s antiviral properties in vitro. Our results support further exploration of fidaxomicin as a therapeutic candidate against SARS‐CoV‐2, given its promising in vitro antiviral activity and favorable safety profile. Drug repurposing is the most suitable approach in emergency cases, like novel virus pandemics. Our well setup machinery, including combined computational and wet lab approaches, managed to output a new antiviral candidate.

Background: This study aimed to investigate the clinical form, risk factors, and outcomes of patients with COVID-19 and Clostridioides difficile co-infections. Methods: This retrospective study (2 September 2021–1 April 2022) included all patients with Clostridioides difficile infection (CDI) and COVID-19 infection who were admitted to the Covid Hospital of the University Clinical Center of Vojvodina. Results: A total of 5124 COVID-19 patients were admitted to the Covid Hospital, and 326 of them (6.36%) developed hospital-onset CDI. Of those, 326 of the CDI patients (88.65%) were older than 65 years. The median time of CDI onset was 12.88 days. Previous hospitalizations showed 69.93% of CDI patients compared to 38.81% in the non-CDI group (p = 0.029). The concomitant antibiotics exposure was higher among the CDI group versus the non-CDI group (88.65% vs. 68.42%, p = 0.037). Albumin levels were ≤ 25 g/L among 39.57% of the CDI patients and 21.71% in the non-CDI patients (p = 0.021). The clinical manifestations of CDI ranged from mild diarrhea (26.9%) to severe diarrhea (63.49%) and a complicated form of colitis (9.81%). Regarding outcomes, 79.14% of the CDI patients recovered and 20.86% had fatal outcomes in-hospital. Although a minority of the patients were in the non-CDI group, the difference in mortality rate between the CDI and non-CDI group was not statistically significant (20.86% vs. 15.13%, p = 0.097). Conclusions: Elderly patients on concomitant antibiotic treatments with hypoalbuminemia and with previous healthcare exposures were the most affected by COVID-19 and CD co-infections.

The aim of the current research is to analyse the relationship between the socioeconomic status (SES) of parents and intellectual abilities (IQ) of preschool children of Serbian territory, and in particular how SES factors relate to preschool children’s IQ measured with Raven’s Coloured Progressive Matrices (CPM), in the different age groups. The research included 430 parents and 430 preschool children. A confirmatory factor analysis of the SES questionnaire revealed five factors: educational and professional status of father and mother, residential and educational status of the family, sport status of parents and comfort of family housing. No gender differences in IQ levels were found in children. Multiple linear regression at four age groups showed that the educational status of the parents and residential and educational status of the family was positively correlated with the IQ at the older groups of preschool children. Two groups of children with the lowest and highest Raven’s CPM scores (1st and 4th quartiles) were used in the Logistic Regression, which determined the significant predictive value of SES factor in children with low Raven’s CPM scores. The results of the current research are in line with other studies on the topic, emphasizing the critical role of social environment for cognitive abilities of children.

Essential oils (EOs) isolated from different plant materials, namely Origanum majorana L., Satureja hortensis L., and Satureja montana L. (OMEO, SHEO, and SMEO, respectively), were used in fresh turkey sausage processing. The chemical composition and in vitro antimicrobial potential of selected EOs and their mixture were determined. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against foodborne pathogens (Escherichia coli, Salmonella Enteritidis, and Listeria monocytogenes) ranged in the interval of 0.44–7.1 µL/mL. Fresh turkey sausages were produced with EOs addition and marked as follows: TOMEO—0.150 µL/g OMEO; TSHEO—0.150 µL/g SHEO; TSMEO—0.150 µL/g SMEO; TEOM—0.050 µL/g OMEO, 0.050 µL/g SHEO and 0.050 µL/g SMEO, and control (C) (without EOs). Microbiological profile and biogenic amines content in fresh turkey sausages were recorded during storage. The selected EOs and their mixture efficiently reduced bacterial growth and biogenic amines formation and accumulation. The lowest Enterobacteriaceae count and total biogenic amine (BA) concentration were determined through treatment TSHEO. The results of this study show that selected EOs could be useful in fresh turkey sausage processing in order to improve safety and shelf-life.

Extracellular vesicles (EVs) are nanoscale particles released by cells and are significant components in intercellular communication. Their ability to reflect the molecular state of parental cells and their presence in body fluids make them increasingly recognized as promising non-invasive biomarkers for different pathological conditions. However, the existence of different EV populations and frequent co-isolation of contaminants present challenges for EV purification and downstream analyses. In this study, we used three novel nanobodies (VHH) for selective isolation of EVs from human plasma. Nanobodies were obtained by direct panning on EVs. All examined nanobodies have excellent physicochemical properties resulting in excellent expression and solubility. The three nanobodies being studied—NA8, ND101, and ND102—share a conserved VHH scaffold but exhibit different loop architectures. The Biopython ProtParam module was used for calculation of VHH physicochemical properties, while sequence alignments for evaluation of variations were performed with the Biopython pairwise2 module. In addition, structural modeling of nanobodies with AlphaFold revealed notable differences in CDR3 conformations. VHH were produced in E. coli, and upon immobilization onto a solid carrier, they were used for immunoaffinity-based capture of EVs from human plasma. Combined characterization of isolated EVs supports efficient application of an immunoaffinity-based system based on such nanobodies for the isolation of EVs from human plasma to be used for downstream analyses.