Single-molecule microfluidic assay for prostate-specific antigen based on magnetic beads and upconversion nanoparticles.

Early-stage diagnosis of prostatic carcinoma is essential for successful treatment and, thus, significant prognosis improvement. In laboratory practice, the standard non-invasive diagnostic approach is the immunochemical detection of the associated biomarker, prostate-specific antigen (PSA). Ultrasensitive detection of PSA is essential for both diagnostic and recurrence monitoring purposes. To achieve exceptional sensitivity, we have developed a microfluidic device with a flow-through cell for single-molecule analysis using photon-upconversion nanoparticles (UCNPs) as a detection label. For this purpose, magnetic microparticles (MBs) were first optimized for the capture and preconcentration of PSA and then used to implement a bead-based upconversion-linked immunoassay (ULISA) in the microfluidic device. The digital readout based on counting single nanoparticle-labeled PSA molecules on MBs enabled a detection limit of 1.04 pg mL-1 (36 fM) in 50% fetal bovine serum, which is an 11-fold improvement over the respective analog MB-based ULISA. The microfluidic technique conferred several other advantages, such as easy implementation and the potential for achieving high-throughput analysis. Finally, it was proven that the microfluidic setup is suitable for clinical sample analysis, showing a good correlation with a reference electrochemiluminescence assay (recovery rates between 97% and 105%).

Revisiting treatment-related cardiotoxicity in patients with malignant lymphoma-a review and prospects for the future.

Treatment of malignant lymphoma has for years been represented by many cardiotoxic agents especially anthracyclines, cyclophosphamide, and thoracic irradiation. Although they are in clinical practice for decades, the precise mechanism of cardiotoxicity and effective prevention is still part of the research. At this article we discuss most routinely used anti-cancer drugs in chemotherapeutic regiments for malignant lymphoma with the focus on novel insight on molecular mechanisms of cardiotoxicity. Understanding toxicity at molecular levels may unveil possible targets of cardioprotective supportive therapy or optimization of current therapeutic protocols. Additionally, we review novel specific targeted therapy and its challenges in cardio-oncology.

Effect of Different Feed Particle Size on Gastrointestinal Tract Morphology, Ileal Digesta Viscosity, and Blood Biochemical Parameters as Markers of Health Status in Broiler Chickens.

The study is focused on how the physical structure of the feed affects the health status of broiler chickens. The aim of this study was to evaluate the influence of feed particle size in broiler diets on gastrointestinal tract morphology, digesta viscosity, and blood biochemical parameters. A total of 90 one-day-old male Ross 308 broiler chickens were randomly divided into three different experimental groups (with five replicates per pen), with 6 birds per cage. The first experimental group (Coarse) was fed with the coarsest particle size, with feed with a geometric mean diameter (GMD) of 1111.26 µm, the next group (Medium) was fed with a less coarse feed size of GMD 959.89 µm, and the last group (Fine) was fed a diet with a fine feed particle size of GMD 730.48 µm. The use of coarse feed particle size in the diet had a positive effect on the gizzard weight and small intestinal villi height and crypt depth, which increased the surface area intended for digesting nutrients. The use of finely ground particles in the feed increased the level of gamma-glutamyl transferase and at the same time, decreased the level of urea, which could indicate adverse changes in the liver.

Emergency medicine pharmacotherapy compromises accuracy of plasma creatinine determination by enzyme-based methods: real-world clinical evidence and implications for clinical practice.

Background: Assessment of kidney function in emergency settings is essential across all medical subspecialties. Daily assessment of patient creatinine results from emergency medical services showed that some deviated from expected values, implying drug-related interference. Methods: Real-time clinical evaluation of an enzyme method (Roche CREP2) in comparison with the Jaffé gen. 2 method (Roche CREJ2) was performed. During the period of December 2022 and January 2023, we analyzed 8,498 patient samples, where 5,524 were heavily medicated STAT patient specimens, 500 were pediatric specimens, and 2,474 were from a distant general population in a different region using the same methods. Results: In 109 out of 5,524 hospital specimens (1.97%, p < 0.001), the CREP2 value was apparently (25% or more) lower than CREJ2. Suspect interfering medication was found in a sample of 43 out of 46 reviewed patients where medication data were available. This phenomenon was not observed in the general population. Conclusion: In a polymedicated urgent care hospital population, a creatinine enzyme method produces unreliable results, apparently due to multiple drug-related interferences.

Caraway (Carum carvi L.) in fast-growing and slow-growing broiler chickens' diets and its effect on performance, digestive tract morphology and blood biochemical profile.

The aim of this study was to evaluate the addition of caraway (1%) in fast-growing and slow-growing broiler chickens' diet and its effect on performance parameters, blood biochemical profile, and relative organ sizes and ileum morphology in slow-growing broilers. Two separated experiments were performed. On the first day of age, the broilers were divided into 2 equal groups (Control and Caraway) with 6 replicates per treatment in both experiments. Experiment I: The total of 276 male fast-growing Ross 308 broiler chickens were used. The trial lasted from the first day to 35th day of chickens' age. Experiment II: The total of 216 male slow-growing (Hubbard JA 57) broilers were used. The trial lasted from the first to 50th day of chickens' age. Mean liveweight, weight gain, feed conversion ratio, blood biochemical parameters, and relative organ sizes were not significantly different in these trials. The group of slow-growing broilers supplemented with 1% of caraway in the diet showed longer villi and deeper crypt in the ileum after 50 d of life. Based on our results, it can be stated that the proportion of 1% caraway in fast-growing and slow-growing broiler chickens' diet did not influence performance parameters, blood biochemical profile and relative organ sizes. In case of the experiment with the slow-growing broilers supplemented with caraway, a significant difference in the height of the villi and the depth of the crypts was found. Caraway can be included in the broiler chickens' diets without negative effects, but further study of the effect on the intestinal morphology is necessary.

Sunitinib-Induced Elevation of Mean Corpuscular Volume (MCV)-Exploring Its Possible Clinical Relevance in Cancer Patients.

Sunitinib is a broad-spectrum multitargeted tyrosine kinase inhibitor mainly used as second-line therapy for non-resectable gastrointestinal stromal or first-line treatment option of metastatic renal cell carcinoma (mRCC), and as an "off-label" option in pediatric oncology. It has been previously reported that sunitinib elevates the mean corpuscular volume of erythrocytes (MCV) in treated subjects. The aim of this study was to assess time-dependent changes of this effect and evaluate its possible clinical relevance. In this study, 179 adult and 21 pediatric patients with solid tumors treated with sunitinib were retrospectively analyzed. The laboratory and treatment-related data were collected for each treatment period. The regression model with a broken-line relationship was used to fit time dependence of the MCV. In the adult group, the MCV was increasing during the first 21.6 weeks (median) of treatment in a median level of 99.8 fL, where it stabilized. MCV increase was faster in the patients who suffered from treatment-related adverse events (21.3 vs. 24.6 weeks, p = 0.010). In the pediatric cohort, the MCV dynamics were similar to adults. In conclusion, MCV changes during sunitinib treatment in pediatric and adult patients may be of clinical utility in monitoring sunitinib treatment course.

Management of Complete Heart Block in a Pregnant Woman with Systemic Lupus Erythematosus-Associated Complications: Treatment Considerations and Pitfalls.

We present a case of a pregnant woman with systemic lupus erythematosus (SLE) who was diagnosed with asymptomatic complete heart block (CHB) during pregnancy. To evaluate possible risks and benefits of pacemaker (PM) implantation, a multidisciplinary counselling board was held. Its recommendation was to perform PM implantation to prevent intra-uterine growth restriction from insufficient cardiac output using a fluoroscopic protective shield. The procedure was performed without complications and established permanent pacing on onwards ECG examinations. The patient subsequently gave birth to a healthy newborn. After a retrospective clinical case evaluation and review of relevant literature, a presumptive association between CHB and the primary diagnosis was proposed. Above that, pregnant women with SLE who develop hypertension are commonly treated with methyldopa, which may cause conduction abnormalities. Clinical recommendations for young female patients expecting pregnancy are lacking in this area. Careful diagnostic and treatment approaches should be used in the management of possible SLE-related complications in women of child-bearing age, focusing on preventable events.

Anti-cancer therapy-induced metabolic syndrome.

The increasing number of long-term survivors that underwent the anti-cancer therapy faces the late treatment-related adverse effects and the increased risk of developing metabolic syndrome. This article defines the pathophysiology that underlies development of anti-cancer therapy-related metabolic syndrome and outlines the possibility of optimisation of comprehensive care focusing on prevention. Considering the preventability of metabolic syndrome, effective screening and follow-up appropriate for patients at increased risk of related adverse events should be established. Subsequently, early initiation of therapy targeting the hallmarks of metabolic syndrome may ease its manifestation in long-term perspective.

B-Cell Activating Factor as a Cancer Biomarker and Its Implications in Cancer-Related Cachexia.

B-cell activating factor (BAFF) is a cytokine and adipokine of the TNF ligand superfamily. The main biological function of BAFF in maintaining the maturation of B-cells to plasma cells has recently made it a target of the first FDA-approved selective BAFF antibody, belimumab, for the therapy of systemic lupus erythematosus. Concomitantly, the role of BAFF in cancer has been a subject of research since its discovery. Here we review BAFF as a biomarker of malignant disease activity and prognostic factor in B-cell derived malignancies such as multiple myeloma. Moreover, anti-BAFF therapy seems to be a promising approach in treatment of B-cell derived leukemias/lymphomas. In nonhematologic solid tumors, BAFF may contribute to cancer progression by mechanisms both dependent on and independent of BAFF's proinflammatory role. We also describe ongoing research into the pathophysiological link between BAFF and cancer-related cachexia. BAFF has been shown to contribute to inflammation and insulin resistance which are known to worsen cancer cachexia syndrome. Taking all the above together, BAFF is emerging as a biomarker of several malignancies and a possible hallmark of cancer cachexia.