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Extracellular nanoparticles (EPs) are a subject of increasing interest for their biological role as mediators in cell–cell communication; however, their harvesting and assessment from bodily fluids are challenging, as processing can significantly affect samples. With the aim of minimizing processing artifacts, we assessed the number density (n) and hydrodynamic diameter (Dh) of EPs directly in diluted plasma and blood using the following recently developed technique: interferometric light microscopy (ILM). We analyzed 613 blood and plasma samples from human patients with inflammatory bowel disease (IBD), collected in trisodium citrate and ethylenediaminetetraacetic acid (EDTA) anticoagulants, and 163 blood and plasma samples from canine patients with brachycephalic obstructive airway syndrome (BOAS). We found a highly statistically significant correlation between n in the plasma and n in the blood only in the human (i.e., but not canine) blood samples, between the samples with trisodium citrate and EDTA, and between the respective Dh for both species (all p < 10−3). In the human plasma, the average was 139 ± 31 nm; in the human blood, was 158 ± 11 nm; in the canine plasma, was 155 ± 32 nm; and in the canine blood, was 171 ± 33 nm. The differences within species were statistically significant (p < 10−2), with sufficient statistical power (P > 0.8). For , we found no statistically significant differences between the human plasma and blood samples or between the samples with trisodium citrate and EDTA. Our results prove that measuring n and Dh of EPs in minimally processed fresh blood and in diluted fresh plasma by means of ILM is feasible for large populations of samples.

Background and Objectives: The subcutaneous (SC) formulation of vedolizumab has proven to be effective for the maintenance of remission after intravenous induction. Little is known about the efficacy of switching from intravenous maintenance treatment to SC. We aimed to assess the real-world efficacy of switching to SC treatment and to assess the impact of a baseline treatment regimen. Materials and Methods: In this observational cohort study, adult patients with inflammatory bowel disease who were switched to SC vedolizumab maintenance treatment were enrolled. Patients after intravenous induction and patients who switched from intravenous maintenance treatment (every 8 weeks or every 4 weeks) were included. The SC vedolizumab dosing was 108 mg every 2 weeks, regardless of the previous regimen. The clinical, biochemical, and endoscopic disease activity parameters and vedolizumab serum concentrations at the time of the switch and at the follow-up were assessed. Results: In total, 135 patients (38% Crohn’s disease, 62% ulcerative colitis) were switched to SC vedolizumab treatment. The median time to the first follow-up (FU) was 14.5 weeks (IQR 12–26), and the median time to the second FU was 40 weeks (IQR 36–52). Nine patients (7%) discontinued SC vedolizumab treatment, with two-thirds of them discontinuing due to active disease. In all dosing regimens, there were no significant changes in the clinical scores and CRP at the baseline and first and second FUs. Clinical and biochemical remission appeared to be maintained irrespective of the previous dosing regimen. Conclusions: The results of this real-world study suggest that the maintenance of clinical and biomarker remission can be achieved in patients who switched from intravenous to SC vedolizumab. The baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.

The authors present and discuss the results of a nation-wide survey on food safety knowledge among professional food handlers in Slovenia. The data were collected via a telephone survey using a well-established questionnaire adapted to the Slovenian context. Altogether, 601 respondents from hotels, restaurants, catering, and confectionery units completed the questionnaire. To assess food safety knowledge among food handlers in both general and specific domains, three indexes (a General Knowledge Index, a Personal Knowledge Index, and a Temperature Knowledge Index) were created. Among them, the Temperature Knowledge Index revealed the largest gaps in knowledge. An insufficient transfer of food safety knowledge from managers and chefs to assistant chefs and kitchen assistants in establishments where more persons handle food was evident, while a course titled “Hygiene Minimum” of standardised training from the past still significantly contributes to food safety knowledge. The results suggest a need for improvement in the current system of food safety training courses for professional food handlers in Slovenia. The human factor in the food supply chain still has a significant role in ensuring food safety culture, and therefore must become a more important part of the food safety management system.

Background and Objectives: The main drawback of lipofilling is fat transplant volume loss, which makes long-term results unreliable. This study’s aim was to assess the influence of an adipose-derived stromal vascular fraction (SVF) on volume retention in large-volume fat grafts. Materials and Methods: A murine model was used for the in vivo evaluation of fat-graft volume changes over 6 months. We used 28 immunocompromised nude NU(NCr)-Foxn1nu mice and human fat tissue as a liposuction by-product. Part of the fat tissue was used for SVF preparation. We created a fat transplant without SVF (SVF-) and with SVF (SVF+) groups. Large-volume grafts were injected above the sacrum and scapula in the same animal. Volume loss was evaluated using three-dimensional optical scanning at 14 days (T1), 3 months (T2), and 6 months (T3) after transplantation. Scans were processed with Artec Studio software to obtain stereolithography files. The volumes were calculated in RapidForm software 2006. Results: The highest volume loss was observed above the scapula at T3 (SVF- 85%; SVF+ 75%). There was a significant difference in volume between SVF-/SVF+ for grafts above the sacrum at T2, with lower loss in SVF+, and the significance became stronger at T3. The difference in volume loss was also significant above the scapula between SVF-/SVF+ at T3. Conclusions: Although we found a beneficial effect of SVF on the long-term survival of large-volume fat tissue transplants, volume loss due to other contributing factors was high.

Ustekinumab is a monoclonal antibody used in Crohn’s disease (CD). Dose optimization in case of non-response and the role of pharmacokinetic–pharmacodynamic (PK-PD) monitoring remain unresolved dilemmas in clinical practice. We aimed to develop a population PK-PD model for ustekinumab in CD and simulate efficacy of alternative dosing regimens. We included 57 patients and recorded their characteristics during 32 weeks after starting with ustekinumab therapy. Serum ustekinumab concentration was prospectively measured and fecal calprotectin (FC) concentration was used to monitor the disease activity. Ustekinumab PK-PD was described by a two-compartment target-mediated drug disposition model linked to an indirect response model. Lower fat-free mass, higher serum albumin, previous non-exposure to biologics, FCGR3A-158 V/V variant and lower C-reactive protein were associated with higher ustekinumab exposure. Model-based simulation suggested that 41.9% of patients receiving standard dosing achieve biochemical remission at week 32. In patients not achieving remission with standard dosing at week 16, transition to 4-weekly subcutaneous maintenance dosing with or without intravenous reinduction resulted in comparably higher remission rates at week 32 (51.1% vs. 49.2%, respectively). Our findings could be used to guide stratified ustekinumab treatment in CD, particularly in patients with unfavorable characteristics, who might benefit from early transition to 4-weekly maintenance dosing.

Plant-derived nanovesicles (NVs) have attracted interest due to their anti-inflammatory, anticancer and antioxidative properties and their efficient uptake by human intestinal epithelial cells. Previously we showed that tomato (Solanum lycopersicum L.) fruit is one of the interesting plant resources from which NVs can be obtained at a high yield. In the course of the isolation of NVs from different batches of tomatoes, using the established differential ultracentrifugation or size-exclusion chromatography methods, we occasionally observed the co-isolation of viral particles. Density gradient ultracentrifugation (gUC), using sucrose or iodixanol gradient materials, turned out to be efficient in the separation of NVs from the viral particles. We applied cryogenic transmission electron microscopy (cryo-TEM), scanning electron microscopy (SEM) for the morphological assessment and LC–MS/MS-based proteomics for the protein identification of the gradient fractions. Cryo-TEM showed that a low-density gUC fraction was enriched in membrane-enclosed NVs, while the high-density fractions were rich in rod-shaped objects. Mass spectrometry–based proteomic analysis identified capsid proteins of tomato brown rugose fruit virus, tomato mosaic virus and tomato mottle mosaic virus. In another batch of tomatoes, we isolated tomato spotted wilt virus, potato virus Y and southern tomato virus in the vesicle sample. Our results show the frequent co-isolation of plant viruses with NVs and the utility of the combination of cryo-TEM, SEM and proteomics in the detection of possible viral contamination.

Despite their high potential, most of the clinically approved iron oxide (IO)-based contrast agents for magnetic resonance imaging (MRI) have been withdrawn from the market either due to safety issues or lack of sales. To address this challenge, erythrocyte membranes have been used to prepare IO-based T2 contrast agents with superior MRI properties and higher safety margin. A simple formulation procedure has been proposed, and the nanostructures’ morphology and physicochemical properties have been evaluated. We compared their performance in terms of contrast ability in MRI to the more clinically established magneto-liposomes and non-encapsulated nanoparticles (NPs). The encapsulation of 5-nm iron oxide nanoparticles (IO NPs) in the liposomes and erythrocyte membrane vesicles (EMVs) led to a significant improvement in their r2 relaxivity. r2 values increased to r2 = 188 ± 2 mM−1s−1 for magneto-liposomes and r2 = 269 ± 3 mM−1s−1 for magneto-erythrocyte membranes, compared to “free” IO NPs with (r2 = 12 ± 1 mM−1 s−1), measured at a 9.4 T MRI scanner. The superiority of magneto-erythrocyte membranes in terms of MRI contrast efficacy is clearly shown on T2-weighted MR images. Our study revealed the hemocompatibility of the developed contrast agents in the MRI-relevant concentration range.

The sensitivity of two commercial metal oxide (MOx) sensors to ethylene is tested at different relative humidities. One sensor (MiCS-5914) is based on tungsten oxide, the other (MQ-3) on tin oxide. Both sensors were found to be sensitive to ethylene concentrations down to 10 ppm. Both sensors have significant response times; however, the tungsten sensor is the faster one. Sensor models are developed that predict the concentration of ethylene given the sensor output and the relative humidity. The MQ-3 sensor model achieves an accuracy of ±9.2 ppm and the MiCS-5914 sensor model predicts concentration to ±7.0 ppm. Both sensors are more accurate for concentrations below 50 ppm, achieving ±6.7 ppm (MQ-3) and 5.7 ppm (MiCS-5914).

A screen printed pH sensor was developed using a PANI layer as a proton sensitive material for the in-situ measurements of matrix cross-linking. The sensor showed a linear response in a broad pH range (3–10) and had an evident cross-talk to Cl− ions. Preliminary in-situ measurements showed a substantial signal change during the cross-linking process.

A rapid advanced packaging concept, consisting of inkjet photopolymer printing and Ag nanoparticles printing, was investigated for the construction of a pressure sensor package. Acrylate-type 3D package housing with 7 through-holes was printed with a polyjet printer and the through-vias and connection pads were manufactured via Ag glue dispensing and inkjet printing of Ag nanoparticle ink. The flip-chip packaging concept was pursued for the electrical connection between the package and the pressure sensor dye.