Interaction of mycotoxins zearalenone, α-zearalenol, and ß-zearalenol with cytochrome P450 (CYP1A2, 2C9, 2C19, 2D6, and 3A4) enzymes and organic anion transporting polypeptides (OATP1A2, OATP1B1, OATP1B3, and OATP2B1).

Zearalenone (ZEN) is a mycoestrogen produced by Fusarium fungi. ZEN is a frequent contaminant in cereal-based products, representing significant health threat. The major reduced metabolites of ZEN are α-zearalenol (α-ZEL) and ß-zearalenol (ß-ZEL). Since the toxicokinetic interactions of ZEN/ZELs with cytochrome P450 enzymes (CYPs) and organic anion transporting polypeptides (OATPs) have been barely characterized, we examined these interactions applying in vitro models. ZEN and ZELs were relatively strong inhibitors of CYP3A4 and moderate inhibitors of CYP1A2 and CYP2C9. Both CYP1A2 and CYP3A4 decreased ZEN and ß-ZEL concentrations in depletion assays, while only CYP1A2 reduced α-ZEL levels. OATPs tested were strongly or moderately inhibited by ZEN and ZELs; however, these mycotoxins did not show higher cytotoxicity in OATP-overexpressing cells. Our results help the deeper understanding of the toxicokinetic/pharmacokinetic interactions of ZEN, α-ZEL, and ß-ZEL.

Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids.

Biological membranes, primarily composed of lipids, envelop each living cell. The intricate composition and organization of membrane lipids, including the variety of fatty acids they encompass, serve a dynamic role in sustaining cellular structural integrity and functionality. Typically, modifications in lipid composition coincide with consequential alterations in universally significant signaling pathways. Exploring the various fatty acids, which serve as the foundational building blocks of membrane lipids, provides crucial insights into the underlying mechanisms governing a myriad of cellular processes, such as membrane fluidity, protein trafficking, signal transduction, intercellular communication, and the etiology of certain metabolic disorders. Furthermore, comprehending how alterations in the lipid composition, especially concerning the fatty acid profile, either contribute to or prevent the onset of pathological conditions stands as a compelling area of research. Hence, this review aims to meticulously introduce the intricacies of membrane lipids and their constituent fatty acids in a healthy organism, thereby illuminating their remarkable diversity and profound influence on cellular function. Furthermore, this review aspires to highlight some potential therapeutic targets for various pathological conditions that may be ameliorated through dietary fatty acid supplements. The initial section of this review expounds on the eukaryotic biomembranes and their complex lipids. Subsequent sections provide insights into the synthesis, membrane incorporation, and distribution of fatty acids across various fractions of membrane lipids. The last section highlights the functional significance of membrane-associated fatty acids and their innate capacity to shape the various cellular physiological responses.

Chemical and Physical Properties of African Catfish (Clarias gariepinus) Fillet Following Prolonged Feeding with Insect Meal-Based Diets.

A 25-week experiment was undertaken to explore the effect of partial replacement of dietary fishmeal (FM) with black soldier fly meal (Hermetia illucens) (BS), mealworm meal (Tenebrio molitor) (MW), and a 1 : 1 mixture of both insect meals (BSMW) on fillet quality in African catfish (Clarias gariepinus). A total of 96 fish with an average initial body weight of 248 ± 28 g were stocked into a recirculating aquaculture system and fed in four different dietary groups (control, BS, MW, and BSMW). No mortality was recorded in any of the groups. At the end of the feeding period, 24 fish (n = 6 for each treatment, weight between 690 and 822 g) were used for analysis. There was no alteration in filleting yield or other slaughter indices within experimental groups, except the hepatosomatic index. Among quality attributes, pH 24 hr postmortem exhibited a significant difference (p < 0.05). In respect of the fatty acid profile, the n-6/n-3 ratio ranged between 1.17 and 1.40 but was not significantly modified by the partial replacement of FM. Similarly, the proximate composition of the fillets was not significantly different between the control and experimental diet groups. The ratio of polyunsaturated fatty acid to saturated fatty acids ranged between 0.67 and 0.79 in the fillets, without significant differences between groups. The atherogenic index was increased in the BS group, as compared to the others; however, the thrombogenicity index of fillets was not significantly affected. Similarly, the conventional quality traits of the fillet, such as cooking, drip, and thawing losses, did not differ within treatments. This study demonstrates that the dietary inclusion of black soldier fly and/or mealworm meals used for African catfish at the tested inclusion level has negligible impact on fillet properties.

Hormonal changes in the first 24 postoperative hours after cardiac surgical procedures.

Background: Hormone level changes after heart surgeries are a widely observed phenomenon due to neurohormonal feedback mechanisms that may affect postoperative morbidity and mortality. The current study aimed to analyze the changes in thyroid and sex hormones in the first 24 postoperative hours after heart surgery. Methods: This prospective, observational study (registered on ClinicalTrials.gov: NCT03736499; 09/11/2018) included 49 patients who underwent elective cardiac surgical procedures at a tertiary heart center between March 2019 and December 2019. Thyroid hormones, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and sex hormones, including prolactin (PRL) and total testosterone, were measured preoperatively and at 24 h postoperatively. Results: Significant decreases in serum TSH (P < 0.001), T3 (P < 0.001) and total testosterone (P < 0.001) levels were noted, whereas T4 (P = 0.554) and PRL (P = 0.616) did not significantly change. Intensive care unit (ICU) hours (P < 0.001), mechanical ventilation (P < 0.001) and Vasoactive-Inotropic Score (VIS) (P = 0.006) were associated with postoperative T3 level. ICU hours were associated with postoperative T4 level (P = 0.028). Postoperative and delta testosterone levels were in connection with lengths of stay in ICU (P = 0.032, P = 0.010 respectively). Model for End-Stage Liver Disease (MELD) scores were associated with thyroid hormone levels and serum testosterone. Conclusions: T3 may represent a marker of nonthyroidal illness syndrome and testosterone may reflect hepatic dysfunction. In addition, PRL may act as a stress hormone in female patients.

Down-Syndrome-Related Maternal Dysbiosis Might Be Triggered by Certain Classes of Antibiotics: A New Insight into the Possible Pathomechanisms.

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations, the role of nutrients, vitamins, and, in general, the foodborne-associated background, as part of the events ultimately leading to chromosome nondisjunction, has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes. The possible association of DS development with maternal gut microbiota should therefore require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa; and hence, we might find associations between the use of the different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N = 30). By utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997-2020) and the estimated prevalence of people living with DS for the year 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

Observation of a Possible Successful Treatment of DEPDC5-Related Epilepsy with mTOR Inhibitor.

The mechanistic target of the rapamycin signaling pathway serves as a central regulator of cell metabolism, growth, proliferation, and survival. In its regulation, the GTPase-activating protein activity toward Rags1 complex has an inhibitory effect. Mutations in genes encoding this complex protein are among the most common abnormalities in focal epilepsies. Within these mutations, the mutations affecting the DEPDC5 gene have been associated with different autosomal dominantly inherited epilepsy types. Due to the limited data available on mTOR inhibitor therapy in nontuberous sclerosis complex epileptic patients, here we present the clinical management of a patient with intractable epilepsy, skin hypopigmentation, and a DEPDC5 variant. The patient's phenotype is compatible with a nonlesional DEPDC5-related epileptic encephalopathy. We initiated compassionate, off-label everolimus treatment as the patient's condition continuously deteriorated. Due to bilateral pneumonia occurring at the beginning of the treatment, it was temporarily discontinued, and resumed in half the dose. Follow-up examination after 18 months showed a 90% reduction in seizure frequency with moderate improvement in attention function and nutritional status. Our case report emphasizes the importance of early genetic testing in patients with epileptic encephalopathy. Clinical consequences of mammalian target of rapamycin complex 1 (mTORC1) upregulation may be amenable to tailored treatment with mTOR inhibitors. A clinical trial on an international scale would be needed to draw conclusions.

New perspectives in application of kidney biomarkers in mycotoxin induced nephrotoxicity, with a particular focus on domestic pigs.

The gradual spread of Aspergilli worldwide is adding to the global shortage of food and is affecting its safe consumption. Aspergillus-derived mycotoxins, including aflatoxins and ochratoxin A, and fumonisins (members of the fusariotoxin group) can cause pathological damage to vital organs, including the kidney or liver. Although the kidney functions as the major excretory system in mammals, monitoring and screening for mycotoxin induced nephrotoxicity is only now a developmental area in the field of livestock feed toxicology. Currently the assessment of individual exposure to mycotoxins in man and animals is usually based on the analysis of toxin and/or metabolite contamination in the blood or urine. However, this requires selective and sensitive analytical methods (e.g., HPLC-MS/MS), which are time consuming and expensive. The toxicokinetic of mycotoxin metabolites is becoming better understood. Several kidney biomarkers are used successfully in drug development, however cost-efficient, and reliable kidney biomarkers are urgently needed for monitoring farm animals for early signs of kidney disease. ß2-microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) are the dominant biomarkers employed routinely in environmental toxicology research, while kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are also emerging as effective markers to identify mycotoxin induced nephropathy. Pigs are exposed to mycotoxins due to their cereal-based diet and are particularly susceptible to Aspergillus mycotoxins. In addition to commonly used diagnostic markers for nephrotoxicity including plasma creatinine, NAG, KIM-1 and NGAL can be used in pigs. In this review, the currently available techniques are summarized, which are used for screening mycotoxin induced nephrotoxicity in farm animals. Possible approaches are considered, which could be used to detect mycotoxin induced nephropathy.

Comprehensive frailty assessment with multidimensional frailty domains as a predictor of mortality among vascular and cardiac surgical patients.

Purpose: The frailty concept has become a fundamental part of daily clinical practice. In this study our purpose was to create a risk estimation method with a comprehensive aspect of patients' preoperative frailty. Patients and methods: In our prospective, observational study, patients were enrolled between September 2014 and August 2017 in the Department of Cardiac Surgery and Department of Vascular Surgery at Semmelweis University, Budapest, Hungary. A comprehensive frailty score was built from four main domains: biological, functional-nutritional, cognitive-psychological and sociological. Each domain contained numerous indicators. In addition, the EUROSCORE for cardiac patients and the Vascular POSSUM for vascular patients were calculated and adjusted for mortality. Results: Data from 228 participants were included for statistical analysis. A total of 161 patients underwent vascular surgery, and 67 underwent cardiac surgery. The preoperatively estimated mortality was not significantly different (median: 2.700, IQR (interquartile range): 2.000-4.900 vs. 3.000, IQR: 1.140-6.000, P = 0.266). The comprehensive frailty index was significantly different (0.400 (0.358-0.467) vs. 0.348 (0.303-0.460), P = 0.001). In deceased patients had elevated comprehensive frailty index (0.371 (0.316-0.445) vs. 0.423 (0.365-0.500), P < 0.001). In the multivariate Cox model an increased risk for mortality in quartiles 2, 3 and 4 compared with quartile 1 as a reference was found (AHR (95% CI): 1.974 (0.982-3.969), 2.306 (1.155-4.603), and 3.058 (1.556-6.010), respectively). Conclusion: The comprehensive frailty index developed in this study could be an important predictor of long-term mortality after vascular or cardiac surgery. Accurate frailty estimation could make the traditional risk scoring systems more accurate and reliable.

Inhibition of mouse trypsin isoforms by SPINK1 and effect of human pancreatitis-associated mutations.

Serine protease inhibitor Kazal type 1 (SPINK1) is a trypsin-selective inhibitor protein secreted by the exocrine pancreas. Loss-of-function SPINK1 mutations predispose to chronic pancreatitis through either reduced expression, secretion, or impaired trypsin inhibition. In this study, we aimed to characterize the inhibitory activity of mouse SPINK1 against cationic (T7) and anionic (T8, T9, T20) mouse trypsin isoforms. Kinetic measurements with a peptide substrate, and digestion experiments with ß-casein indicated that the catalytic activity of all mouse trypsins is comparable. Human SPINK1 and its mouse ortholog inhibited mouse trypsins with comparable efficiency (KD range 0.7-2.2 pM), with the sole exception of T7 trypsin, which was inhibited less effectively by the human inhibitor (KD 21.9 pM). Characterization of four chronic pancreatitis-associated human SPINK1 mutations in the context of the mouse inhibitor revealed that the reactive-loop mutations R42N (human K41N) and I43M (human I42M) impaired SPINK1 binding to trypsin (KD 60 nM and 47.5 pM, respectively), whereas mutations D35S (human N34S) and A56S (human P55S) had no impact on trypsin inhibition. Our results confirmed that high-affinity trypsin inhibition by SPINK1 is conserved in the mouse, and the functional consequences of human pancreatitis-associated SPINK1 mutations can be replicated in the mouse inhibitor.

Gut-Faecal Microbial and Health-Marker Response to Dietary Fumonisins in Weaned Pigs.

This study investigated effects of dietary fumonisins (FBs) on gut and faecal microbiota of weaned pigs. In total, 18 7-week-old male pigs were fed either 0, 15 or 30 mg FBs (FB1 + FB2 + FB3)/kg diet for 21 days. The microbiota was analysed with amplicon sequencing of the 16S rRNA gene V3-V4 regions (Illumina MiSeq). Results showed no treatment effect (p > 0.05) on growth performance, serum reduced glutathione, glutathione peroxidase and malondialdehyde. FBs increased serum aspartate transaminase, gamma glutamyl-transferase and alkaline phosphatase activities. A 30 mg/kg FBs treatment shifted microbial population in the duodenum and ileum to lower levels (compared to control (p < 0.05)) of the families Campylobacteraceae and Clostridiaceae, respectively, as well as the genera Alloprevotella, Campylobacter and Lachnospiraceae Incertae Sedis (duodenum), Turicibacter (jejunum), and Clostridium sensu stricto 1 (ileum). Faecal microbiota had higher levels of the Erysipelotrichaceae and Ruminococcaceae families and Solobacterium, Faecalibacterium, Anaerofilum, Ruminococcus, Subdoligranulum, Pseudobutyrivibrio, Coprococcus and Roseburia genera in the 30 mg/kg FBs compared to control and/or to the 15 mg/kg FBs diets. Lactobacillus was more abundant in the duodenum compared to faeces in all treatment groups (p < 0.01). Overall, the 30 mg/kg FBs diet altered the pig gut microbiota without suppressing animal growth performance.

Overlapping Interstitial Deletions of the Region 9q22.33 to 9q33.3 of Three Patients Allow Pinpointing Candidate Genes for Epilepsy and Cleft Lip and Palate.

Introduction: Patients carrying interstitial deletions of the long arm of chromosome 9 show similar features. These phenotypes are often characterized by developmental delay, intellectual disability, short stature, and dysmorphism. Previously reported deletions differ in size and location spanning from 9q21 to 9q34 and were mostly detected by conventional cytogenetic techniques. Methods: Based on clinical features suggesting primarily chromosomal diseases, aCGH analysis was indicated. We report on de novo overlapping interstitial 9q deletions in 3 unrelated individuals presenting neurodevelopmental disorder and multiple congenital anomalies. Results: An 8.03-Mb (90 genes), a 15.71-Mb (193 genes), and a 15.81-Mb (203 genes) deletion were identified in 9q affecting 9q22.33q33.3. The overlapping region was 1.50 Mb, including 2 dosage-sensitive genes, namely EPB41L4B (OMIM #610340) and SVEP1 (OMIM #611691). These genes are thought to be involved in cellular adhesion, migration, and motility. The non-overlapping regions contain 24 dosage-sensitive genes. Conclusion: Besides the frequently described symptoms (developmental delay, intellectual disability, skeletal abnormalities, short stature, and dysmorphic facial features) shared by the patients with interstitial deletions of chromosome 9q reported thus far, two of our patients showed distinct forms of epilepsy, which were successfully treated, and one had a bilateral cleft lip and palate. Possible candidate genes for epilepsy and cleft lip and palate are discussed.

Zymosan Particle-Induced Hemodynamic, Cytokine and Blood Cell Changes in Pigs: An Innate Immune Stimulation Model with Relevance to Cytokine Storm Syndrome and Severe COVID-19.

Hemodynamic disturbance, a rise in neutrophil-to-lymphocyte ratio (NLR) and release of inflammatory cytokines into blood, is a bad prognostic indicator in severe COVID-19 and other diseases involving cytokine storm syndrome (CSS). The purpose of this study was to explore if zymosan, a known stimulator of the innate immune system, could reproduce these changes in pigs. Pigs were instrumented for hemodynamic analysis and, after i.v. administration of zymosan, serial blood samples were taken to measure blood cell changes, cytokine gene transcription in PBMC and blood levels of inflammatory cytokines, using qPCR and ELISA. Zymosan bolus (0.1 mg/kg) elicited transient hemodynamic disturbance within minutes without detectable cytokine or blood cell changes. In contrast, infusion of 1 mg/kg zymosan triggered maximal pulmonary hypertension with tachycardia, lasting for 30 min. This was followed by a transient granulopenia and then, up to 6 h, major granulocytosis, resulting in a 3-4-fold increase in NLR. These changes were paralleled by massive transcription and/or rise in IL-6, TNF-alpha, CCL-2, CXCL-10, and IL-1RA in blood. There was significant correlation between lymphopenia and IL-6 gene expression. We conclude that the presented model may enable mechanistic studies on late-stage COVID-19 and CSS, as well as streamlined drug testing against these conditions.

Characterization of Danube Swabian population samples on a high-resolution genome-wide basis.

BACKGROUND: German-derived ethnicities are one of the largest ethnic groups in Hungary, dating back to the formation of the Kingdom of Hungary, which took place at the beginning of the 11th century. Germans arrived in Hungary in many waves. The most significant immigration wave took place following the collapse of the Ottoman Empire in East-Central Europe which closed the 150 year long Ottoman occupation. To date, there are no comprehensive genome-wide studies investigating the genetic makeup of the Danube Swabians. Here we analyzed 47 Danube Swabian samples collected from elderly Swabian individuals living in the Dunaszekcso-Bár area, in Danube side villages of Southwest Hungary. These Swabians, according to self-declaration, did not admix with other ethnic groups for 3-6 succeeding generations. Using Illumina Infinium 720 K Beadchip genotype data, we applied allele frequency-based and haplotype-based genome-wide marker data analyses to investigate the ancestry and genetic composition of the collected Danube Swabian samples. RESULTS: Haplotype-based analyses like identity by descent segment analysis show that the investigated Danube Swabians possess significant German and other West European ancestry, but their Hungarian ancestry is also prominent. Our results suggest that their main source of ancestry can be traced back to Western Europe, presumably to the region of Germany. CONCLUSION: This is the first analysis of Danube Swabian population samples based on genome-wide autosomal data. Our results establish the basis for conducting further comprehensive research on Danube Swabians and on other German ethnicities of the Carpathian basin, which can help reconstruct their origin, and identify their major archaic genomic patterns.

Expanding SPTAN1 monoallelic variant associated disorders: From epileptic encephalopathy to pure spastic paraplegia and ataxia.

PURPOSE: Nonerythrocytic αII-spectrin (SPTAN1) variants have been previously associated with intellectual disability and epilepsy. We conducted this study to delineate the phenotypic spectrum of SPTAN1 variants. METHODS: We carried out SPTAN1 gene enrichment analysis in the rare disease component of the 100,000 Genomes Project and screened 100,000 Genomes Project, DECIPHER database, and GeneMatcher to identify individuals with SPTAN1 variants. Functional studies were performed on fibroblasts from 2 patients. RESULTS: Statistically significant enrichment of rare (minor allele frequency < 1 × 10-5) probably damaging SPTAN1 variants was identified in families with hereditary ataxia (HA) or hereditary spastic paraplegia (HSP) (12/1142 cases vs 52/23,847 controls, p = 2.8 × 10-5). We identified 31 individuals carrying SPTAN1 heterozygous variants or deletions. A total of 10 patients presented with pure or complex HSP/HA. The remaining 21 patients had developmental delay and seizures. Irregular αII-spectrin aggregation was noted in fibroblasts derived from 2 patients with p.(Arg19Trp) and p.(Glu2207del) variants. CONCLUSION: We found that SPTAN1 is a genetic cause of neurodevelopmental disorder, which we classified into 3 distinct subgroups. The first comprises developmental epileptic encephalopathy. The second group exhibits milder phenotypes of developmental delay with or without seizures. The final group accounts for patients with pure or complex HSP/HA.

Effects of Surface Treatment with Thymol on the Lipid Oxidation Processes, Fatty Acid Profile and Color of Sliced Salami during Refrigerated Storage.

The oxidation of unsaturated fatty acids and the adverse transformation of pigments from meat and spices are the primary causes of chemical degradation in processed meat products. Thymol is found in a variety of plant extracts that have been proven to effectively inhibit or slow down oxidative processes. The objective of our study was to determine whether thymol treatment of the surface of sliced paprika salami could be applied to inhibit lipid oxidation and color change during refrigerated storage. During eight weeks of storage, the malondialdehyde (MDA) levels and the ratios of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and n6/n3 in thymol-treated salami remained unchanged (p ≥ 0.05), whereas in the controls, the MDA levels increased by approximately twelvefold and the ratio of SFAs in the lipid fraction increased (p < 0.001), while the ratio of PUFAs decreased (p < 0.001). The application of thymol prevented decrease in yellowness (b*) of the slices and reduced decreases in redness (a*) and brightness (chroma).

[Diagnosis of genetic disorders in childhood with next-generation sequencing]. / Gyermekkori genetikai rendellenességek diagnosztikája újgenerációs szekvenálással.

Incorporating next-generation sequencing (NGS) technology to diagnostics enables to identify a vast repertoire of genetic disorders in a single measurement. Currently, targeted gene panels and whole-exome sequencing (WES) are the most prevalent methods in clinical use due to the smaller cost of analysis and manageable amount of data compared to whole-genome sequencing (WGS). We aim to review the applicability of NGS-based technologies in the diagnosis of early-onset genetic disorders. We summarize genes associated with early-onset diseases including inborn errors of metabolism, oncological indications and pediatric genetic disorders. There are several technical and clinical issues that currently limit the everyday diagnostic application of NGS. The principal challenge lies in the interpretation of rare genetic variants and in the correct assignment of variant pathogenicity. Orv Hetil. 2022; 163(51): 2027-2040.

Association between Hepatic Venous Congestion and Adverse Outcomes after Cardiac Surgery.

INTRODUCTION: Hepatic venous flow patterns reflect pressure changes in the right ventricle and are also markers of systemic venous congestion. Fluid management is crucial in patients undergoing cardiac surgery. METHODS: Our goal was to determine which factors are associated with the increased congestion of the liver as measured by Doppler ultrasound in patients undergoing cardiac surgery. This prospective, observational study included 41 patients without preexisting liver disease who underwent cardiac surgery between 1 January 2021 and 30 September 2021 at a tertiary heart center. In addition to routine echocardiographic examination, we recorded the maximal velocity and velocity time integral (VTI) of the standard four waves seen in the common hepatic vein (flow profile) using Doppler ultrasound preoperatively and at the 20-24th hour of the postoperative period. The ratios of the retrograde and anterograde hepatic venous waves were calculated, and the waveforms were compared to the baseline value and expressed as a delta ratio. Demographic data, pre- and postoperative echocardiographic parameters, intraoperative variables (procedure, cardiopulmonary bypass time), postoperative factors (fluid balance, vasoactive medication requirement, ventilation time and parameters) and perioperative laboratory parameters (liver and kidney function tests, albumin) were used in the analysis. RESULTS: Of the 41 patients, 20 (48.7%) were males, and the median age of the patients was 65.9 years (IQR: 59.8-69.9 years). Retrograde VTI growth showed a correlation with positive fluid balance (0.89 (95% CI 0.785-0.995) c-index. After comparing the postoperative echocardiographic parameters of the two subgroups, right ventricular and atrial diameters were significantly greater in the "retrograde VTI growth" group. The ejection fraction and decrement in ejection fraction to preoperative parameters were significantly different between the two groups. (p = 0.001 and 0.003). Ventilation times were longer in the retrograde VTI group. The postoperative vs. baseline delta VTI ratio of the hepatic vein correlated with positive fluid balance, maximum central venous pressure, and ejection fraction. (B = -0.099, 95% CI = -0.022-0.002, p = 0.022, B = 0.011, 95% CI = 0.001-0.021, p = 0.022, B = 0.091, 95% CI = 0.052-0.213, p = 0.002, respectively.) Conclusion: The increase of the retrograde hepatic flow during the first 24 h following cardiac surgery was associated with positive fluid balance and the decrease of the right ventricular function. Measurement of venous congestion or venous abdominal insufficiency seems to be a useful tool in guiding fluid therapy and hemodynamic management.

Micro-Encapsulated Microalgae Oil Supplementation Has No Systematic Effect on the Odor of Vanilla Shake-Test of an Electronic Nose.

In this study, we aimed to carry out the efficient fortification of vanilla milkshakes with micro-encapsulated microalgae oil (brand: S17-P100) without distorting the product's odor. A 10-step oil-enrichment protocol was developed using an inclusion rate of 0.2 to 2 w/w%. Fatty acid (FA) profile analysis was performed using methyl esters with the GC-MS technique, and the recovery of docosahexaenoic acid (C22:6 n3, DHA) was robust (r = 0.97, p < 0.001). The enrichment process increased the DHA level to 412 mg/100 g. Based on this finding, a flash-GC-based electronic nose (e-nose) was used to describe the product's odor. Applying principal component (PC) analysis to the acquired sensor data revealed that for the first four PCs, only PC3 (6.5%) showed a difference between the control and the supplemented products. However, no systematic pattern of odor profiles corresponding to the percentages of supplementation was observed within the PC planes. Similarly, when discriminant factor analysis (DFA) was applied, though a classification of the control and supplemented products, we obtained a validation score of 98%, and the classification pattern of the odor profiles did not follow a systematic format. Again, when a more targeted approach such as the partial least square regression (PLSR) was used on the most dominant sensors, a weak relationship (R2 = 0.50) was observed, indicating that there was no linear combination of the qualitative sensors' signals that could accurately describe the supplemented concentration variation. It can therefore be inferred that no detectable off-odor was present as a side effect of the increase in the oil concentration. Some volatile compounds of importance in regard to the odor, such as ethylacetate, ethyl-isobutarate, pentanal and pentyl butanoate, were found in the supplemented product. Although the presence of yeasts and molds was excluded from the product, ethanol was detected in all samples, but with an intensity that was insufficient to cause an off-odor.

Admission lactate level and the GRACE 2.0 score are independent and additive predictors of 30-day mortality of STEMI patients treated with primary PCI-Results of a real-world registry.

BACKGROUND: In many of the risk estimation algorithms for patients with ST-elevation myocardial infarction (STEMI), heart rate and systolic blood pressure are key predictors. Yet, these parameters may also be altered by the applied medical treatment / circulatory support without concomitant improvement in microcirculation. Therefore, we aimed to investigate whether venous lactate level, a well-known marker of microcirculatory failure, may have an added prognostic value on top of the conventional variables of the "Global Registry of Acute Coronary Events" (GRACE) 2.0 model for predicting 30-day all-cause mortality of STEMI patients treated with primary percutaneous coronary intervention (PCI). METHODS: In a prospective single-center registry study conducted from May 2020 through April 2021, we analyzed data of 323 cases. Venous blood gas analysis was performed in all patients at admission. Nested logistic regression models were built using the GRACE 2.0 score alone (base model) and with the addition of venous lactate level (expanded model) with 30-day all-cause mortality as primary outcome measure. Difference in model performance was analyzed by the likelihood ratio (LR) test and the integrated discrimination improvement (IDI). Independence of the predictors was evaluated by the variance inflation factor (VIF). Discrimination and calibration was characterized by the c-statistic and calibration intercept / slope, respectively. RESULTS: Addition of lactate level to the GRACE 2.0 score improved the predictions of 30-day mortality significantly as assessed by both LR test (LR Chi-square = 8.7967, p = 0.0030) and IDI (IDI = 0.0685, p = 0.0402), suggesting that the expanded model may have better predictive ability than the GRACE 2.0 score. Furthermore, the VIF was 1.1203, indicating that the measured lactate values were independent of the calculated GRACE 2.0 scores. CONCLUSIONS: Our results suggest that admission venous lactate level and the GRACE 2.0 score may be independent and additive predictors of 30-day all-cause mortality of STEMI patients treated with primary PCI.

Fumonisin B Series Mycotoxins' Dose Dependent Effects on the Porcine Hepatic and Pulmonary Phospholipidome.

Male weaned piglets n = 6/group were fed Fumonisin B1+2+3 (FBs) mycotoxins at 0, 15, or 30 mg/kg diet for 3 weeks to assess the fatty acid (FA) composition of membrane lipid classes, lipid peroxidation, and histomorphological changes in the liver and lung. Growth performance and lipid peroxidation were unaltered, but histomorphological lesion scores increased in the liver. Linear dose-response was detected in liver phosphatidylcholines for C16:1n7, C18:1n9, and total monounsaturation and in lungs for C22:6n3, total n-3 and n-3:n-6, in pulmonary phosphatidylserines C20:0 and C24:0. Alterations associated with the highest FBs dose were detected in sphingomyelins (liver: total saturation ↓, total monounsaturation ↑), phosphatidylcholines (liver: total n-6 ↓, n-6:n-3 ↑; in lungs: total monounsaturation ↑, total polyunsaturation ↑), phosphatidylethanolamines (liver: total n-3 ↓; in lungs: total monounsaturation ↑ and n-6:n-3 ↑), phosphatidylserines (liver: n-6:n-3 ↑; in lungs: total saturation ↓, total polyunsatuartion ↑, and total n-6 and its ratio to n-3 ↑), and phosphatidylinositol (n-6:n-3 ↑; lungs: C22:1n9 ↑, C22:6n3 ↓, total saturation ↓, total monounsaturaion ↑). In conclusion, FBs exposures neither impaired growth nor induced substantial lipid peroxidation, but hepatotoxicity was proven with histopathological alterations at the applied exposure period and doses. FA results imply an enzymatic disturbance in FA metabolism, agreeing with earlier findings in rats.