Blood Concentrations Research Articles

Enantiomeric profile of amphetamines in seized drug samples and in blood of impaired drivers in Iceland: the rise of (R)-methamphetamine?

Amphetamine (AMP) and methamphetamine (METH) use is increasing globally. Illegal AMP is generally a racemic mixture, whereas AMP-containing attention-deficit hyperactivity disorder drugs prescribed in Iceland consist of S-AMP. AMP is also a main metabolite of interest after METH intake. Distinguishing between legal and illegal AMP intake is vital in forensic toxicology. A chiral UPLC-MS/MS method was used to determine the enantiomeric profile of AMP and METH in circulation in Iceland by analysing blood samples from drivers suspected of driving under the influence of drugs (DUID) and seized drug samples from 2021 and 2022. All seized AMP samples (n = 48) were racemic, whereas all but one seized METH sample (n = 26) were enantiopure. Surprisingly, a large portion of the enantiopure METH samples was R-METH. DUID blood samples positive for AMP (n = 564) had a median blood concentration of 180 ng/mL (range 20-2770 ng/mL) and a median enantiomeric fraction (EFR) of 0.54 (range 0-0.73), whereas samples positive for METH (n = 236) had a median blood concentration of 185 ng/mL (range 20-2300 ng/mL) and a median EFR of 0.23 (range 0-1). The findings of this study show a significantly lower blood concentration in drivers with only S-AMP detected compared with when the R-isomer is also detected. No significant difference in blood concentration was detected between the sample groups containing S-METH, R-METH, or both enantiomers. The occurrence of R-METH in both seized drug samples and DUID cases indicates a change in drug supply and a need for better scientific knowledge on R-METH abuse.

Evaluation of 68Ga-PSMA-11 PET/CT: a Phase 1 clinical study in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer.

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals allow whole-body imaging to detect prostate cancer (PC). Positron emission tomography imaging using gallium-68 (68Ga)-PSMA-11 has been shown to have a favorable safety and tolerability profile and high diagnostic performance. The study evaluates the safety and pharmacokinetics of 68Ga-PSMA-11 in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer. This single arm study enrolled Japanese patients with primary PC (n = 3), suspected recurrent PC following radical prostatectomy (n = 4), or suspected recurrent PC following radical radiotherapy (n = 3). All patients received a single intravenous dose of 68Ga-PSMA-11 2.0MBq/kg (±10%) followed by PSMA PET imaging and safety and pharmacokinetic evaluations. Based on the blood concentrations of 68Ga-PSMA-11 and the radioactivity distribution rate in each organ/tissue, the absorbed doses in major organs/tissues and the whole-body effective dose were calculated by the Medical Internal Radiation Dose method. Ten patients were enrolled. Mean age was 73.3 ± 4.8years, and median prostate-specific antigen was 8.250 ng/mL. Five patients (50%) experienced a total of 6 adverse events, and no grade ≥ 2 adverse events or serious adverse events were reported. No clinically significant changes in vital signs, haematology parameters, or blood chemistry or ECG abnormalities were observed. The estimated whole body effective dose of 68Ga-PSMA-11 (mean ± standard deviation) was 2.524 × 10-2 ± 2.546 × 10-3mSv/MBq. Time to maximum concentration (1.16 × 10-4 ± 1.3 × 10-5% ID/mL) in whole blood was 2.15 ± 0.33min. 68Ga-PSMA-11 has a favourable safety and tolerability profile in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer, which is comparable to previous observations in other populations.

Developing a machine learning model for predicting venlafaxine active moiety concentration: a retrospective study using real-world evidence.

Venlafaxine is frequently prescribed for patients with depression. To control the concentration of venlafaxine within the therapeutic window for the best treatment effect, a model to predict venlafaxine concentration is necessary. Our objective was to develop a prediction model for venlafaxine concentration using real-world evidence based on machine learning and deep learning techniques. Patients who underwent venlafaxine treatment between November 2019 and August 2022 were included in the study. Important variables affecting venlafaxine concentration were identified using a combination of univariate analysis, sequential forward selection, and machine learning techniques. Predictive performance of nine machine learning and deep learning algorithms were assessed, and the one with the optimal performance was selected for modeling. The final model was interpreted using SHapley Additive exPlanations. A total of 330 eligible patients were included. Five influential variables that affect venlafaxine concentration were venlafaxine daily dose, sex, age, hyperlipidemia, and adenosine deaminase. The venlafaxine concentration prediction model was developed using the eXtreme Gradient Boosting algorithm (R2 = 0.65, mean absolute error = 77.92, root mean square error = 93.58). In the testing cohort, the accuracy of the predicted concentration within ± 30% of the actual concentration was 73.49%. In the subgroup analysis, the prediction accuracy was 69.39% within the recommended therapeutic range of venlafaxine concentration within ± 30% of the actual value. The XGBoost model for predicting blood concentration of venlafaxine using real-world evidence was developed, guiding the adjustment of regimen in clinical practice.

Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-Institutional Prospective Cohort Evaluation.

Neoadjuvant chemotherapy (NAC) is linked with clinical advantages in urothelial carcinoma for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive research into the influence of tumor mutation expression profiles and clinicopathological factors on chemotherapy response, the role of the gut microbiome (GM) in bladder cancer(BC) chemotherapy response remains poorly understood. This study examines the variance in the gut microbiome(GM) of BC patients compared to healthy adults, and investigates GM compositional differences between patients who respond to chemotherapy versus those who exhibit residual disease. Our study reveals distinct clustering, effectively separating the BC and healthy cohorts. However, no significant differences were observed between chemotherapy responders and non-responders within community subgroups. Machine Learning models based on responder status outperformed clinical variables in predicting complete response (AUC 0.88 vs AUC 0.50), although no single microbial species emerged as a fully reliable biomarker. The evaluation of short-chain fatty acid (SCFA) concentration in blood and stool revealed no correlation with responder status. Still, SCFA analysis showed a higher abundance of Akkermansia (rs = 0.51, p = 0.017) and Clostridia (rs = 0.52, p = 0.018), which correlated with increased levels of detectable fecal isobutyric acid. Higher levels of fecal Lactobacillus (rs = 0.49, p=0.02) and Enterobacteriaceae (rs = 0.52, p < 0.03) correlated with increased fecal propionic acid. In conclusion, our study constitutes the first large-scale, multi-center assessment of GM composition, suggesting the potential for a complex microbial signature to predict patients more likely to respond to NAC based on multiple taxa.

Compatibility study of topical 0.25% hypericin (HyBryteTM) application in subjects with mycosis fungoides: Results of the HPN‐CTCL‐02 study

AbstractBackgroundHyBryteTM is a photodynamic therapy of topical hypericin that has recently been shown to be safe and efficacious in early stage cutaneous T‐cell lymphoma (CTCL). However, its efficacy, absorption, and effect on heart function parameters in patients who require greater HyBryteTM exposure is unknown.ObjectivesThe primary objectives in this study were to assess hypericin blood levels using a validated detection method with a cut‐off value of 0.05 ng/mL and to determine if topical HyBryteTM induces any electrocardiogram (EKG) changes during 8 weeks of treatment. A secondary endpoint of this study was to assess the effectiveness of HyBryteTM in this patient population as well as assessing a different additional light device than the one used in the Phase 3 HPN‐CTCL‐01/fluorescent light activated synthetic hypericin trial also entitled “A phase 3 multicenter randomised placebo‐controlled study to determine the efficacy of topical hypericin and light irradiation for the treatment of cutaneous T‐cell lymphoma”.MethodsA confirmatory, prospective, open‐label, single‐centre, interventional study focused on stage IB and IIA mycosis fungoides with more than 10% of their body surface areas involved was performed.ResultsHypericin concentration in K2EDTA whole blood samples collected before and after light activation at Weeks 4, 6 and 8 showed an average blood concentration of 0.13 ng/mL and achieved steady state by Week 4. EKGs were examined for clinical changes at each study visit, including changes in QT intervals and correction of heart rates. No significant clinical changes in EKGs were observed.ConclusionsHypericin does not appear to be significantly absorbed through the skin nor cause significant cardiac changes overall or prolong the QT interval when applied topically. A larger study is necessary to clearly define these results.

Selenium and Arsenic Levels, Prevalence of Common Variants of Genes Involved in Their Metabolism, and Psoriasis Disease

Using an Inductively Coupled Plasma Mass Spectrometer we measured the concentration of selenium and arsenic in serum and blood samples from 336 unselected psoriatic patients and 336 matched healthy controls to evaluate any associations with the clinical course of the disease. We genotyped 336 patients and 903 matched controls to evaluate the prevalence of SOD2 (rs4880), CAT (rs1001179), GPX1 (rs1050450), and DMGDH (rs921943) polymorphisms using Taqman assays. The mean selenium (Se) level in serum was 74 µg/L in patients and 86 µg/L in controls (p &lt; 0.001). The mean Se level in blood was 95 µg/L in patients and 111 µg/L in controls (p &lt; 0.001). Psoriasis risk was greatest among participants with the lowest serum (&lt;68.75 µg/L, OR: 8.30; p &lt; 0.001) and lowest blood concentrations of Se (&lt;88.04 µg/L, OR: 10.3; p &lt; 0.001). Similar results were observed in subgroups of males and females. We found an inverse correlation of selenium levels with PASI, NAPSI, and BSA scores. There was no significant difference in the distribution of the CAT, GPX1, DMGDH, and SOD2 polymorphisms. Among carriers of rs4880, rs1001179, and rs921943 polymorphisms, blood selenium levels were significantly lower. The mean arsenic level in serum was 0.79 µg/L in patients and 0.7 µg/L in controls (p = 0.2). The mean concentration in blood was 1.1 µg/L in patients and 1.3 µg/L in controls (p &lt; 0.001). In conclusion, we found that lower selenium levels, in blood and serum, are associated with psoriasis risk and its more severe course. Future prospective studies should focus on the optimalisation of the concentration of this trace element not only for prophylactic guidance but also to support the treatment of this disease.

Timing and dosage of intrapartum prophylactic penicillin for preventing early-onset group B streptococcal disease: assessing maternal and umbilical cord blood concentration

ObjectiveTiming of administration of antibiotics and concentrations in maternal blood and the umbilical cord blood are important prerequisites for optimal intrapartum antibiotic prophylaxis (IAP) of neonatal early-onset group B streptococcus...

Effects of dietary nitrogen and/or phosphorus reduction on mineral homeostasis and regulatory mechanisms in young goats

IntroductionThe reduction of nitrogen (N) and phosphorus (P) in ruminant feed is desirable due to costs and negative environmental impact. Ruminants are able to utilize N and P through endogenous recycling, particularly in times of scarcity. When N and/or P were reduced, changes in mineral homeostasis associated with modulation of renal calcitriol metabolism occurred. The aim of this study was to investigate the potential effects of dietary N- and/or P-reduction on the regulatory mechanisms of mineral transport in the kidney and its hormonal regulation in young goats.ResultsDuring N-reduction, calcium (Ca) and magnesium (Mg) concentrations in blood decreased, accompanied by a lower protein expression of cytochrome P450 family 27 subfamily B member 1 (CYP27B1) (p = 0.016). The P-reduced fed goats had low blood phosphate concentrations with simultaneously high Ca and Mg levels. The insulin-like growth factor 1 concentrations decreased significantly with P-reduction. Furthermore, gene expression of CYP27B1 (p &amp;lt; 0.001) and both gene (p = 0.025) and protein (p = 0.016) expression of the fibroblast growth factor receptor 1c isoform in the kidney were also significantly reduced during a P-reduced diet. ERK1/2 activation exhibited a trend toward reduction in P-reduced animals. Interestingly, calcitriol concentrations remained unaffected by either restriction individually, but interacted significantly with N and P (p = 0.014). Additionally, fibroblast growth factor 23 mRNA expression in bone decreased significantly with P-restriction (p &amp;lt; 0.001).DiscussionThese results shed light on the complex metabolic and regulatory responses of mineral transport of young goats to dietary N and P restriction.

Association between rumination behavior, hyperketonemia and milk production in early lactation

Increased blood beta-hydroxybutyrate (BHB), also known as hyperketonemia (HYK), is a common metabolic disorder in dairy cows, that occurs during first and second week postpar­tum, defined by elevated blood concentration of BHB ( ≥ 1.2 mmol/L). HYK is associated with impaired health, decreased performance, and decreased milk production. Nonetheless, ele­vated BHB concentrations in early lactation are not detrimental to all cows. Past studies from our group found that cows with HYK that had high milk production had similar performance (pregnancy rates and herd removal risk) to non-hyperketone­mic cows that also had high milk production. Moreover, there are reports showing that rumination time in the first week post­partum and milk production are positively correlated, with ani­mals that have a high rumination time producing more milk. For these reasons, our objective was to evaluate whether rumi­nation behavior modified the association between blood BHB concentration during the first week postpartum and milk yield during the first 3 herd tests.

Recommended dosages of analgesic and sedative drugs in intensive care result in a low incidence of potentially toxic blood concentrations

Background: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated. Methods: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS). Results: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations. Conclusion: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

Exercise attenuates high-fat diet-induced PVAT dysfunction through improved inflammatory response and BMP4-regulated adipose tissue browning

BackgroundPerivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways.MethodsSprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed.ResultsChronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p &amp;lt; 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p &amp;lt; 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT.ConclusionRegular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.

A non-invasive blood glucose detection using a slotted microstrip antenna sensor

Abstract A novel highly sensitive and compact slotted microstrip antenna sensor is designed consisting of slots with defected ground structure (DGS). The substrate used in the design of antenna is FR-4 of concise dimensions 30 × 30 × 1.6 mm3 and the developed antenna resonates at 3 GHz. The human finger consisting of several layers namely bone, blood, fat and skin is modelled in the EM simulation (CST) environment resulting in finger phantom. The finger phantom is situated at different locations on proposed antenna for evaluating the concentrations of glucose from 0 to 1000 mg/dL and the corresponding shift in frequencies are estimated. For detection of glucose concentration in human blood, the obtained frequency shifts in the proposed work are used. In this proposed work, at the top side of proposed antenna, the finger phantom is situated, an uttermost shift in frequency of 48 MHz, sensitivity of 48 KHz/(mg/dL) and a least possible shift in frequency of 24 MHz, sensitivity of 24 KHz/(mg/dL) are obtained.&amp;#xD;

Early life exposure to mercury and relationships with telomere length and mitochondrial DNA content in European children

BackgroundTelomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL. MethodsStudy participants are 6–11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run. ResultsWe found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46 % increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38 % an increase in TL for each unit increased THg until reaching a cut-point at 0.96 μg/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found. DiscussionWe found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.

Validity of Umbilical Cord Blood Procalcitonin in the Diagnosis of Early-Onset Neonatal Infection.

Early-onset neonatal infection (EONI) poses significant risks to neonatal health, necessitating reliable diagnostic markers for early detection. This study aims to evaluate the diagnostic validity of procalcitonin (PCT) concentration in umbilical cord blood as a biomarker for EONI. This prospective study was conducted at Ho Chi Minh University Medical Center from April 2022 to September 2022. The PCT level was measured in umbilical cord blood at birth. Based on clinical, laboratory, and microbiologic results, neonates were classified into infected and non-infected groups. One hundred eighty neonates with risk factors for EONI were recruited. Among the neonates studied, 22 (12.2%) were classified as infected and 158 (87.8%) as non-infected by the classification criteria of clinical manifestations, laboratory tests, and blood culture. The median PCT in the infected group was significantly higher than that in the non-infected group (0.389 ng/mL vs. 0.127 ng/mL, p = 0.007). The optimal PCT cut-off was found by receiver operating characteristic (ROC) to be 0.23 ng/mL, with an area under the curve (AUC) of 0.87. The results were 59.1%, 98.7%, 86.2%, 94%, 45, and 0.41 for sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios, respectively. The post-test probability was 86% if the test was positive and 5% if it was negative. Umbilical cord blood PCT might be a reliable marker in the diagnosis of EONI, and its value helps limit the harmful effects of unnecessary prescriptions in non-infected neonates. However, considering the low sensitivity of procalcitonin, further research is necessary to fully integrate this biomarker into clinical practice.

Analysis of injuries in aircraft accident victims in 2002–2022 based on the resources of the Jagiellonian University Department of Forensic Medicine in Kraków = Analiza obrażeń ofiar katastrof lotniczych w latach 2002–2022 na podstawie danych pochodzących z materiałów Zakładu Medycyny Sądowej Uniwersytetu Jagiellońskiego w Krakowie

Aim: The study aimed to analyse the most common injuries of victims of aviation accidents and compare it with the most recent literature. Methods and materials: Retrospective analysis of autopsy protocols of aircraft crash victims from the Forensic Medicine Department from years 2002–2022. The case selection has been made by two independent researchers. After applying the exclusion criteria 27 cases were obtained. Further searched for features that the bodies of victims had in common. There were analysed sex, age, circumstances of the incident, injuries, presence of psychoactive substances (alcohol, drugs), and blood concentration of carboxyhemoglobin. Results: Among 27 cases we found 19 airplane crashes, 4 glider accidents, 3 motor glider accidents, and one helicopter crash. The 1 case had no information about the type of aircraft. The injuries that emerged in each of the victims were typical results of direct impact forces. The most common were rupture of the lungs 63.0 % (n = 17/27), heart 55.6% (n = 15/27), liver 51.9% (n = 14/27), aorta 40.7% (n = 11/27) and spleen 29.6% (n = 8/27). Common bone traumas included fractures of the ribs 77.8% (n = 21/27) upper limbs 77.8% (n = 21/27), skull 74.1% (n = 20/27), pelvis 59.3% (n = 16/27) and spine 51.9% (n = 14/27). Injuries of the cervical spine occurred in victims who violently tilted their heads back. Conclusions: In most cases, the immediate cause of death was extensive multi-organ injuries, followed by thermal burns or brain injuries. In almost half of the victims, the presence of carboxyhemoglobin in the blood indicates that they were alive during the crashes. Knowledge of injury patterns can improve aviation safety and guide in reconstructing the mechanisms and sequences of the accidents.

Effect of Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

Drug concentration in blood or urine is an acknowledged method to detect non-adherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension and reduced adherence to antihypertensive drugs. Patients were ≥18 years on stable treatment with at least two antihypertensive agents. We planned to randomize 80 non-adherent patients with a systolic daytime ambulatory BP (ABPM) ≥135 mmHg to TDM-intervention or not. The control group and the study-personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on disease process and importance of BP treatment were given to both groups. From 2017 to 2022, we randomized 46 diagnosed non-adherent from a total of 606 patients with uncontrolled hypertension. The TDM-group had a 6.7 (±14.5) mmHg reduction from 147.9 (±10.3) to 141.1 (±14.1) mmHg, and the control group experienced a 7.3 (±13.2) mmHg reduction from 147.1 (±9.2) to 139.1 (±17.4) mmHg, p=0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at three months, p=0.51. In our prospective multicenter clinical trial of uncontrolled and non-adherent hypertensive patients, we found no additional effect of therapeutic drug monitoring (TDM) on blood pressure and drug adherence compared with standard care.

Evaluation of the Metabolite Profile of Fish Oil Omega-3 Fatty Acids (n-3 FAs) in Micellar and Enteric-Coated Forms—A Randomized, Cross-Over Human Study

This study evaluated the differences in the metabolite profile of three n-3 FA fish oil formulations in 12 healthy participants: (1) standard softgels (STD) providing 600 mg n-3 FA; (2) enteric-coated softgels (ENT) providing 600 mg n-3 FA; (3) a new micellar formulation (LMF) providing 374 mg n-3 FA. The pharmacokinetics (PKs), such as the area under the plot of plasma concentration (AUC), and the peak blood concentration (Cmax) of the different FA metabolites including HDHAs, HETEs, HEPEs, RvD1, RvD5, RvE1, and RvE2, were determined over a total period of 24 h. Blood concentrations of EPA (26,920.0 ± 10,021.0 ng/mL·h) were significantly higher with respect to AUC0-24 following LMF treatment vs STD and ENT; when measured incrementally, blood concentrations of total n-3 FAs (EPA/DHA/DPA3) up to 11 times higher were observed for LMF vs STD (iAUC 0-24: 16,150.0 ± 5454.0 vs 1498.9 ± 443.0; p ≤ 0.0001). Significant differences in n-3 metabolites including oxylipins were found between STD and LMF with respect to 12-HEPE, 9-HEPE, 12-HETE, and RvD1; 9-HEPE levels were significantly higher following the STD vs. ENT treatment. Furthermore, within the scope of this study, changes in blood lipid levels (i.e., cholesterol, triglycerides, LDL, and HDL) were monitored in participants for up to 120 h post-treatment; a significant decrease in serum triglycerides was detected in participants (~20%) following the LMF treatment; no significant deviations from the baseline were detected for all the other lipid biomarkers in any of the treatment groups. Despite a lower administered dose, LMF provided higher blood concentrations of n-3 FAs and certain anti-inflammatory n-3 metabolites in human participants—potentially leading to better health outcomes.

Association between decreased cord blood inter-alpha inhibitor levels and neonatal encephalopathy at birth

BackgroundInter-alpha inhibitor proteins (IAIPs) are structurally related proteins found in the systemic circulation with immunomodulatory anti-inflammatory properties. Reduced levels are found in inflammatory related conditions including sepsis and necrotizing enterocolitis, and in neonatal rodents after exposure to hypoxia ischemia. In the current study, cord blood IAIP levels were measured in neonates with and without exposure to hypoxic-ischemic encephalopathy (HIE). MethodsThis is a prospective cohort study including infants born ≥36 weeks over a one-year period. Term pregnancies were divided into two groups: a “reference control” (uncomplicated term deliveries), and “moderate to severe HIE” (qualifying for therapeutic hypothermia). IAIPs were quantified using a sensitive ELISA on the cord blood samples. ResultsThe study included 57 newborns: Reference control group (n = 13) and moderate/severe HIE group (n = 44). Measurement of IAIP cord blood concentrations in moderate to severe HIE group [278.2 (138.0, 366.0) μg/ml] revealed significantly lower IAIP concentrations compared with the control group [418.6 (384.5, 445.0) μg/ml] (p = 0.002). ConclusionsThese findings suggest a potential role for IAIPs as indicators of neonates at risk for HIE. IAIP levels could have diagnostic implications in the management of HIE. Future research is required to explore the relationship between HIE and IAIPs as biomarkers for disease severity. Category of studyTranslational.

249 A nutritional solution based on calcidiol (25-OH-D3, HyD) and triterpenoid improves growth performance in grower-finisher pigs fed low Ca and P diets without compromising bone health

Abstract Nutritional strategies to realize the genetic potential of modern pigs without compromising welfare while reducing environmental impact are critical for success in the swine industry today. By harnessing the potential of 25-OH-D3, it is possible to fine-tune mineral utilization, thereby allowing for the reduction of excessive calcium (Ca) and phosphorus (P), while promoting bone development and muscle deposition in finisher pigs [1]. A study was conducted using 60 male pigs [initial body weight (BW) = 29.9 kg ± 0.5 kg] to evaluate the effect of reducing dietary Ca and P and supplementing with 25-OH-D3 and triterpenoid, on growth, bone and blood characteristics. Pigs entered the experimental room at 10 wk of age and were randomly allocated to one of six pens in groups of 10. Pigs had a 2-wk adaptation where they were offered a grower diet (NE:12.3MJ, CP:17.5%) before receiving their respective treatments from 12 wk (NE:11.5MJ, CP:16.19%). Three experimental diets were evaluated for 7 wk; Positive control: 0.7% total Ca, 0.36% total P, vit D3 at 1,500 IU/kg feed (PC), negative control: PC diet + 30% reduced Ca and 10% reduced P (NC), and NC diet with 1,500 IU D3, in calcidiol form (25-OH-D3, HyD) and triterpenoid (NC+). Pigs had ad libitum access to feed which was recorded individually via automated electronic feeders. At slaughter, blood was collected, and body and carcass composition scans were taken from pigs using dual-energy x-ray absorptiometry (DXA) and metacarpals were collected. Data were analyzed in JMP17.0 using one-way ANOVA, including treatment as a main effect and 10-wk weight as a covariate, with pig as the experimental unit. Table 1 shows the results. Pigs offered NC+ tended to have a heavier slaughter weight compared with NC, with PC being intermediate (P = 0.08). There were no differences in feed-intake, but NC+ increased average daily gain compared with NC (P = 0.03), and NC+ tended to be more efficient (P = 0.08). The DXA-scan demonstrated that bone mineral density and content in NC+ pigs were comparable with PC and NC. Additionally, reducing Ca and P in NC resulted in reduced ash, Ca and P in the metacarpals. Interestingly, NC+ had similar bone P content to PC, indicating that NC+ allows for reduced Ca and P, without compromising bone composition. As expected, NC+ had greater 25-OH-D3 blood concentrations (P &amp;lt; 0.001). Although there was no difference in blood for Ca, P concentrations were greater in NC+ compared with other groups (P = 0.007), suggesting that NC+ allowed for greater P circulating concentrations, despite being reduced in the diet. In conclusion, supplementing a reduced Ca and P diet with calcidiol and triterpenoid can enhance weight gain and feed-conversion as well as improving blood 25-OH-D3 and bone P concentrations. The use of this solution shows that diets can be formulated to be more sustainable without compromising performance or bone-health.

86 Assessment of sow hemoglobin concentration and its impact on farrowing duration

Abstract Prolonged farrowing duration may have detrimental effects on sows, leading to physical strain and potential complications post farrowing. Severe hypoxia experienced by piglets during farrowing can result in stillbirths or birth of weak piglets, increasing the likelihood of pre-weaning mortality. While the prevalence of anemia in sows has recently gained attention, the consequences of this condition are not yet well understood. Blood concentration of hemoglobin (Hb) has a role in oxygen carrying capacity and thus may influence the resilience of a sow during farrowing. Evaluating Hb in sows before farrowing could offer insights for improving sow welfare and reducing pre-weaning mortality. The primary objective of this study was to examine the relationship between sow Hb and farrowing duration. A total of 57 sows (n = 5, 6, 29, and 17 of parity 1, 2, 3, and 4, respectively) were monitored for Hb using a Hemocue Hb 201+ handheld Hb monitor where sow blood samples were collected before farrowing (on d 112) and between 40 and 48 h after farrowing (i.e., on d 2) from an ear vein using a 20 G needle. Sows were categorized as anemic (Hb &amp;lt; 10 g/dL) or non-anemic (Hb ≥ 10 g/dL) based on their Hb at d 112. Among sows that were evaluated, 25 were classified as non-anemic- and 32 were classified as anemic. Surveillance cameras were employed to record the farrowing process for each sow, accompanied by human observation. The time of birth for each piglet was recorded to calculate average birthing interval. Within 12 h of birth, all piglets were weighed individually. Stillborn piglets were identified using a lung flotation test conducted within 1 h of birth. The correlation between sow Hb, farrowing duration, stillborn piglets, and total piglets born was evaluated using the PROC CORR procedure and Proc Mixed in SAS was used to test the effect of Hb category on farrowing duration with total piglets born as a covariate. A negative correlation was observed between pre-farrow Hb and farrowing duration (r = -0.62, P &amp;lt; 0.0001). No correlation was observed between farrowing duration and total born (r = 0.22, P = 0.11). However, a significant weak correlation was found between farrowing duration and stillborn piglets (r = 0.32, P = 0.01). Anemic sows had prolonged farrowing duration (7.2 h ± 0.92 min, P = 0.0005) compared with non-anemic sows (3.5 h ± 0.88 min, P = 0.0005). There was no difference in litter size (16.41 ± 0.7 vs 16.3 ± 0.7) for anemic and non-anemic sows, respectively. These findings highlight the importance of sow Hb status at farrowing and indicate sows with decreased Hb may experience prolonged farrowing duration. Strategies to identify anemic sows before farrowing may reduce stillborn rate and improve sow resilience after farrowing.