Low Blood Concentrations Research Articles

Are there differences in the adaptive profile of hair sheep and their crosses with wool breeds?

This study aimed to evaluate and compare the physiological performance of different genetic groups of sheep, by physiological variables and serum hormone levels, in a hot weather environment. Thirty sheep from five genetic groups were used: Santa Inês (SI), ½ Dorper + ½ Santa Inês (DO), ½ Ilê de France + ½ Santa Inês (IF), ½ Suffolk + ½ Santa Inês (SK), and ½ Texel + ½ Santa Inês (TX). The readings and records of physiological parameters (respiratory rate (RR), rectal temperature (RT), auricular cavity temperature (ACT), and surface temperature (ST)) were carried out at 7:00 am, 1:00pm, and 7:00pm, in 12 non-consecutive days. The collections of blood samples for hormone analysis (triiodothyronine (T3), thyroxine (T4), and cortisol (CORT)) is in four consecutive days. The environmental conditions of the experimental period caused a thermal discomfort in the sheep, but not a state of thermal stress. The thermolysis mechanisms, sensitive (ST and ACT) and latent (RR) processes, were enough to maintain their homeostasis (RT). The results showed that crossbred breeds presented a higher metabolism and were more efficient at dissipating heat through thermolysis than the SI breed. The crossbred breeds were efficient at dissipating heat through the elevation of body surface temperature and respiratory rate, mainly SK and TX, i.e., crossbred breeds, despite the wool cover, used thermoregulatory mechanisms that promoted lower variation of RT. The analysis of variance showed significant effects (P < 0.05) to the time factor in the responses of T4 and T3, and to the breed factor in the responses of CORT, T4, and T3. We did not observe interaction between the factors to any of the hormonal variables. Therefore, we can state that the effect of time was independent of breed and vice versa. Thyroid hormones presented lower blood concentration in the mornings (4.03 ± 0.82, T4; 65.08 ± 10.6, T3), increasing their concentration in the afternoon (4.60 ± 1.03, T4; 70.16 ± 14.17, T3). The thyroid hormones presented a normal circadian rhythm, with the exception of SK. Air temperature (AT) showed greater correlation with physiological variables than enthalpy (H) did, in the experimental conditions. However, H showed correlation with T4 and T3. The adaptive profile of the genetic groups under study are different, but the IF genetic group showed better performance under environmental conditions.

The Effects of Omega-3 Fatty Acid Supplementation on the Lipid Profile and Cardiovascular Markers Following Downhill Running in Long-Distance Runners.

Exercise-induced injury may intensify inflammatory response and reduce the cardiovascular protection mechanisms of omega 3 polyunsaturated fatty acids (ω 3 PUFA). Therefore, this study aimed to determine the erythrocyte content of fatty acids (ω 3 and ω 6), the levels of cardiac damage markers (CKMB, hsTnT, H - FABP), the concentration of inflammation mediators (IL-6, TNF α) in long distance runners supplemented with ω 3 PUFA. Twenty-four male long distance runners, who were randomly assigned to a placebo group (GrP) or a group supplemented (GrSuppl) with a daily dose of 3,000 mg of ω 3 PUFA for three weeks, participated in the study. Participants performed a downhill running exercise test. Blood samples were collected at rest and after the exercise protocol to analyse the levels of cardiac markers and inflammatory cytokines. The erythrocyte membrane content of EPA and DHA in the GrSuppl at the 3rd week of supplementation was significantly higher than at the baseline (p < 0.001). The erythrocyte membrane content of ω 3 PUFA in the GrSuppl was significantly higher at the completion of supplementation (p < 0.001). Supplementation with ω 3 PUFA improved blood lipid profiles and reduced the concentration of inflammation mediators measured after the eccentric exercise tests. The increased ω 3 PUFA content in the erythrocyte membrane and lower blood concentrations of cardiac damage markers and inflammation mediators in distance runners supplemented for three weeks with ω 3 PUFA suggest that the cardiovascular function has been improved.

Cord Blood Metabolite Profiles and Their Association with Autistic Traits in Childhood.

Autism Spectrum Disorder (ASD) is a diverse neurodevelopmental condition. Gene-environmental interactions in early stages of life might alter metabolic pathways, possibly contributing to ASD pathophysiology. Metabolomics may serve as a tool to identify underlying metabolic mechanisms contributing to ASD phenotype and could help to unravel its complex etiology. In a population-based, prospective cohort study among 783 mother-child pairs, cord blood serum concentrations of amino acids, non-esterified fatty acids, phospholipids, and carnitines were obtained using liquid chromatography coupled with tandem mass spectrometry. Autistic traits were measured at the children's ages of 6 (n = 716) and 13 (n = 648) years using the parent-reported Social Responsiveness Scale. Lower cord blood concentrations of SM.C.39.2 and NEFA16:1/16:0 were associated with higher autistic traits among 6-year-old children, adjusted for sex and age at outcome. After more stringent adjustment for confounders, no significant associations of cord blood metabolites and autistic traits at ages 6 and 13 were detected. Differences in lipid metabolism (SM and NEFA) might be involved in ASD-related pathways and are worth further investigation.

Association of human leukocyte antigen-G and -F with recurrent miscarriage and implantation failure: A systematic review and meta-analysis.

The immune system plays an essential role in embryonic implantation and pregnancy, but the molecular details remain controversial. In the past four decades, human leukocyte antigen (HLA)-G and -F have garnered significant attention. MEDLINE, EMBASE, Web of Science, and the Cochrane Trials Registry were searched from their inception dates until December 2022. Studies were selected following PRISMA guidelines. Meta-analyses were used to assess the relationship of soluble HLA-G (sHLA-G) and HLA-G 3'-untranslated region polymorphisms with recurrent miscarriage (RM) and recurrent implantation failure (RIF). Narrative synthesis was conducted to determine the association of RM with other single nucleotide polymorphisms (SNPs) and HLA-G protein in tissues and of RIF with HLA-F. Risk-of-bias was assessed using ROBINS-I. Publication bias was assessed using Egger's and Begg's tests. Finally, 42 articles were eligible for inclusion in the systematic review (32 in the meta-analysis; 13 in narrative synthesis). We found a significant association between the 14-bp ins/del HLA-G polymorphism and RM risk, but no definitive association with RIF risk. Women with RM had lower blood concentrations of sHLA-G during pregnancy and non-pregnancy than did controls. For women in the RIF group, no significant difference was found. HLA-G protein and gene expression levels may be closely related to RM. The relevance of HLA-G to RIF is still being determined. A narrative synthesis of current studies has shown that HLA-F is likely associated with RIF.

B-031 Digital Elisatotal 25-Hydroxyvitamin D

Abstract Evaluation of digital ELISA using a high-resolution computational optical system for measurement of total 25-hydroxyvitamin D Background Biomarkers such as vitamin D occur at very low concentrations in blood, and sensitive detection methods are required in order to measure them. It is difficult to accurately measure low-concentration biomarkers using conventional enzyme-linked immunosorbent assays (ELISA) with fluorescence staining. By developing a digital ELISA (DELISA, Small Machines, Seoul, Korea) platform, a low concentration substance was realized by analyzing the digitalized signal through a high-resolution computational optical system in a microfluidic chip. We evaluated DELISA for measurement of total 25-hydroxyvitamin D (25OHD) in a fluidic chip. Methods The sample with monoclonal antibody bead conjugates mixture was incubated for 20 min at 37°C, then 30 uL sample mixture was applied to inlet of the chip. After additional incubation for 2 min at room temperature and 2 min after sample application, 120 uL of washing buffer was applied onto the washing hole and the chip was incubated for 10 min. 25OHD molecules in the sample bond to magnetic beads coupled with anti-25OHD at the end of the membrane. Chips were inserted into DELISA, and 25OHD results were derived by analysis of the computational method of microscopic imaging, proportional to the concentration of 25OHD. Assay performance characteristics of the limit of detection (LoD), precision and analytical measurement interval (AMI) using Vitamin D Depleted, Low and High Serum (Molecular Depot, San Diego, CA) were determined according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. 87 Samples for method comparison studies were obtained from routine clinical samples submitted for 2 OHD determination or from apparently healthy normal volunteers. The study was approved by the Institutional Review Board of Dongguk University Ilsan Hospital (202207024). Results LoD was 10.3 ng/mL and within-laboratory precision was 11, 12, and 10% coefficient of variation at 14.1, 56.6, and 113.2 ng/mL, respectively. The best fit polynomial was a cubic equation from 14.1 to 113.2 ng/mL and the difference between the third-order equation and the first-order equation at Level 3 and 4 concentrations was outside the non-linearity limit. Comparison with chemiluminescent assay (Elecsys Vitamin D total II, Roche Diagnostics, Mannheim, Germany) yielded a 0.904 of correlation coefficient and 0.921 slope in the range from 7.0 to 57.9 ng/mL. Conclusions The DELISA 25OHD assay has a suitable LoD and precision, however, it is necessary to improve the AMI at high concentration values and correlation with the automated analyzer.

Relación entre el perfil oxidativo y el índice de diversidad de la dieta en adultos mayores de una zona urbano-marginal de Costa Rica

Background and objectiveThe older we get, the greater the production of reactive oxygen species and therefore the greater the oxidative stress, which is related to the deterioration of the health of older adults. This study analyzed the relationship between the oxidative profile and the dietary diversity index in an urban-marginal population of older adults in Costa Rica. MethodsEighty-eight older adults were studied and various markers of oxidative stress, serum glucose levels, lipid profile, and some micronutrients were determined. In addition, the body mass index (BMI) was calculated and the dietary diversity index (DDI) was determined. ResultsLipid peroxidation and DNA oxidation, a mean plasma antioxidant capacity percentage of 39.54±10.67%, which decreased with age, were evidenced. 67% of the participants had alterations in glycemia, 73% had one or more alterations in blood lipid levels, 55% had insufficient vitamin D levels, and 68.6% were overweight. The average IDD was 4.91 points, indicating that the diet was not very diverse. No relationship was found between IDD and nutritional status, between nutritional status and oxidative stress, nor between biochemical variables and oxidative stress. ConclusionThe adults studied presented high oxidative stress, a high percentage of overweight, and a low IDD. A higher IDD was associated with a lower blood concentration of MDA and a higher % PAC.

The Nobel Prize in Physiology 1977: A literature review of the Radioimmunoassay Technique

The first study about radioimmunoassay was published in 1960 by 2 scientists, who created this new method to quantify human insulin, at a time when studies on diabetes and its pathophysiology were beginning to stand out. Years later, due to its strong relevance to the scientific world, such work was awarded the Nobel Prize in Physiology in 1977. Thus, the present study aims to expose the historical context of the discovery, the initial studies on diseases whose immunological origin was still unknown, the beginning of radioimmunoassay techniques and their potential benefits and effects for science. Therefore, a narrative review of the literature was carried out using the PubMed, Scielo and Google Scholar databases in order to find the theoretical bases that underlie the objective of the present study. The study revealed that through the use of radioisotopes for insulin labeling and the use of antibodies from animals, it was possible to quantify hormones at low blood concentrations, based on the graphic of the proportion between free marked insulin and insulin combined with antibodies. Such discovery was important to understand the pathophysiology of many diseases, although on the other hand it presents its risks because it involves radioactive material and because it is now in disuse due to the creation of methods such as ELISA. It is concluded that due to the historical and scientific importance of the RIA, this method proved to be worthy of the most renowned scientific award in the world.

Physical activity attenuates the association between blood cadmium exposure and cardiovascular disease: findings from the National Health and Nutrition Examination Survey 2007-2018.

Existing studies could not separate the effects of heavy metal exposure on cardiovascular disease (CVD) risk from those caused by physical activity (PA). The possible interactive effect of heavy metal exposure and PA on the risk of CVD remains still unknown. We enrolled a total of 12,280 participants in 2007-2018 cycles of the U.S. National Health and Nutrition Examination Survey (NHANES) and discovered that both low blood concentrations of Cd and Pb were positively correlated with increased prevalence of CVD and subtypes, with a stronger association for blood Cd than Pb. Negative dose-response relationships between PA and the prevalence of CVD and subtypes were identified. Participants with inactive and active PA had lower risk of CVD than those having no PA, with multivariate adjusted ORs 0.8 (95% CI: 0.69, 0.94) and 0.76 (95% CI: 0.68, 0.85), respectively. The only evidence for negative interaction between regular PA and blood Cd concentrations was found with regard to the prevalence of CVD and subtypes, indicating that regular PA could well modify the adverse effect of blood Cd on CVD risk. We demonstrate for the first time to date that PA may have a beneficial effect against the hazardous impact of Cd exposure on elevated CVD risk, emphasizing the necessity to promote a healthy lifestyle with active PA.

Pharmacogenetics of Lethal Opioid Overdose: Review of Current Evidence and Preliminary Results from a Pilot Study.

There has been a worldwide substantial increase in accidental opioid-overdose deaths. The aim of this review, along with preliminary results from our pilot study, is to highlight the use of pharmacogenetics as a tool to predict causes of accidental opioid-overdose death. For this review, a systematic literature search of PubMed® between the time period of January 2000 to March 2023 was carried out. We included study cohorts, case-controls, or case reports that investigated the frequency of genetic variants in opioid-related post-mortem samples and the association between these variants and opioid plasma concentrations. A total of 18 studies were included in our systematic review. The systematic review provides evidence of the use of CYP2D6, and to a lower extent, CYP2B6 and CYP3A4/5 genotyping in identifying unexpectedly high or low opioid and metabolite blood concentrations from post-mortem samples. Our own pilot study provides support for an enrichment of the CYP2B6*4-allele in our methadone-overdose sample (n = 41) compared to the anticipated frequency in the general population. The results from our systematic review and the pilot study highlight the potential of pharmacogenetics in determining vulnerability to overdose of opioids.

EVALUATION OF THYROID FUNCTION MARKERS IN TYPE 2 DIABETIC PATIENTS IN RELATION TO INSULIN RESISTANCE

Diabetes mellitus (DM) and thyroid disorders are both caused by endocrine abnormalities, and both have been shown to have a reciprocal influence and frequently coexist. Hence, the current study aims to detect the thyroid functions markers among patients with Type 2 diabetes (T2DM). In this research study, 90 enrolled participants aged 40 to 60 years were taken as samples for the study. There were 66 with T2DM and 24 who were non diabetic healthy individual. All individuals were investigated in terms of age, gender, diabetes duration, glycemic control (HbA1c), fasting blood glucose (FBG), diabetic complications, Body mass index (BMI), waist circumference (WC), and family history of DM. Samples were to assess serum thyroid hormones (TSH, FT3 and FT4), HbA1c, FBG, and insulin levels. The study's findings showed higher glucose incidence, hyperinsulinemia and higher insulin resistance (IR) in diabetic patients. Additionally, it has been noted that T2DM patients have low TSH concentrations and elevated blood concentrations of FT4 and FT3 than controls. Moreover, there was a highly significant correlation between serum FT4 and FT3 with values of FBG, insulin and IR. Also, a significant association between WC with insulin and Homa – Ir was noted. In conclusion, the diabetic patients showed significant relations with thyroid functions status.

Personalization of Anticoagulant Therapy with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease Based on Pharmacogenetic Testing

Background. Polymorphic variants of the genes encoding these isoenzymes and carrier proteins involved in the pharmacokinetics of direct oral anticoagulants (DOAC) may alter their function and, therefore, hypothetically may increase the risk of bleeding associated with the use of DOAC. Aims to study the possible relationship between the presence of polymorphic variants of ABCB1 (rs2032582, rs1045642, rs1128503), CYP3A5 (rs776746) and CYP3A4 (rs35599367) genes on the residual equilibrium concentration (Cmin,ss /D) of apixaban, CYP3A isoenzyme activity and bleeding development in patients with AF and CKD C3C4 stages. Methods. The study included 142 patients with AF combined with chronic CKD stages C3 and C4, receiving apixaban therapy, aged 58 to 99 years (median age 84 years). Pharmacogenetic, pharmacokinetic testing and assessment of CYP3A isoenzyme group activity were performed. Results. Plasma concentration of apixaban depended on the stage of CKD: a higher level of Cmin,ss /D was observed in patients with CKD stage C4 compared to patients with CKD stage C3a and with CKD stage C3b. When studying the effect of rs1045642 (C3435T) polymorphism of ABCB1 gene on apixaban pharmacokinetics, it was found that carriers of homozygous TT genotype had lower median apixaban concentration in blood compared to carriers of CC and TC genotypes (p = 0.027 and 0.034 respectively). For rs2032582 polymorphism of ABCB1 gene, we recorded that patients with GG genotype had higher Cmin,ss /D level of apixaban compared to GT genotype carriers (p = 0.037). CYP3A metabolic activity was statistically significantly lower (p = 0.036) in the group with a history of bleeding compared with that in patients in the group without a history of bleeding (0.8 (0.5; 1.3) and 1.2 (0.7; 2.1); p = 0.036). CYP3A metabolic activity did not differ between patients with different CYP3A5 (rs776746) and CYP3A4 (rs35599367) polymorphism genotypes. For the rs1045642 polymorphic variant, there were fewer carriers of the heterozygous TC genotype (16 (45.7%) patients) among patients with bleeding during the follow-up period compared to patients with no bleeding (43 (53.1%) patients; p = 0.024). Conclusions. The results of the study indicate the presence of an association between genome-wide changes (polymorphic variants of the ABCB1 (rs1045642) and CYP3A5 (rs776746) gene and the presence of apixaban-associated bleeding in patients with AF and CKD stages 34. Mechanisms of such an association require further study.

Intestines-erythrocytes-mediated bio-disposition deciphers the hypolipidemic effect of berberine from Rhizoma Coptidis: A neglected insight

Ethnopharmacological relevanceRhizoma Coptidis (RC), the dried rhizome of Coptis Chinensis Franch., can dispel dampness and heat within the body and has been traditionally used for the treatment of cardiovascular disease (CVD)-associated problems including hyperlipidemia in China. Berberine (BBR) is the main active component of RC, which has been shown to possess significant therapeutic potential. However, only 0.14% of BBR is metabolized in the liver, and the extremely low bioavailability (<1%) and blood concentration of BBR in experimental and clinical settings is insufficient to achieve the effects as observed under in vitro conditions, which imposes challenges to explain its excellent pharmacological actions. Intense efforts are currently being devoted to defining its specific pharmacological molecular targets, while the exploration from the perspective of its pharmacokinetic disposition has rarely been reported to date, which could hardly make a comprehensive understanding of its hypolipidemic enigma. Aim of the studyThis study made a pioneering endeavor to unveil the hypolipidemic mechanism of BBR from RC focusing on its unique intestines-erythrocytes-mediated bio-disposition. Materials and methodsThe fate of BBR in intestines and erythrocytes was probed by a rapid and sensitive LC/MS-IT-TOF method. To analyze the disposition of BBR, a reliable HPLC method was subsequently developed and validated for simultaneous determination of BBR and its key active metabolite oxyberberine (OBB) in whole blood, tissues, and excreta. Meanwhile, the enterohepatic circulation (BDC) of BBR and OBB was verified by bile duct catheterization rats. Finally, lipid overloading models of L02 and HepG2 cells were employed to probe the lipid-lowering activity of BBR and OBB at in vivo concentration. ResultsThe results showed that BBR underwent biotransformation in both intestines and erythrocytes, and converted into the major metabolite oxyberberine (OBB). The AUC0-t ratio of total BBR to OBB was approximately 2:1 after oral administration. Besides, the AUC0-t ratio of bound BBR to its unbound counterpart was 4.6:1, and this ratio of OBB was 2.5:1, indicative of abundant binding-type form in the blood. Liver dominated over other organs in tissue distribution. BBR was excreted in bile, while the excretion of OBB in feces was significantly higher than that in bile. Furthermore, the bimodal phenomenon of both BBR and OBB disappeared in BDC rats and the AUC0-t was significantly lower than that in the sham-operated control rats. Interestingly, OBB significantly decreased triglycerides and cholesterol levels in lipid overloading models of L02 and HepG2 cells at in vivo-like concentration, which was superior to the prodrug BBR. ConclusionsCumulatively, BBR underwent unique extrahepatic metabolism and disposition into OBB by virtue of intestines and erythrocytes. BBR and OBB were mainly presented and transported in the protein-bound form within the circulating erythrocytes, potentially resulting in hepatocyte targeting accompanied by obvious enterohepatic circulation. The unique extrahepatic disposition of BBR via intestines and erythrocytes conceivably contributed enormously to its hypolipidemic effect. OBB was the important material basis for the hypolipidemic effect of BBR and RC.

Synergistic Effects of a Probiotic Culture Extract and Antimicrobial Combinations against Multidrug-Resistant Acinetobacter baumannii.

Background and Objectives: Developing effective treatment outcomes for multidrug-resistant Acinetobacter baumannii (MRAB) infections, with colistin and tigecycline the current frontline therapies, is challenging, because of the risk of renal toxicity and low blood concentrations of active ingredients when administered intravenously. This study aimed to identify the effect of combination therapy using conventional antimicrobial agents that are used for treating drug-resistant bacteria and the additional synergistic effect of four probiotic culture extracts isolated from the human body and Lactobacillus preparations. Materials and Methods: The antimicrobial combination and synergistic effect of adding Lactobacillus extract against 33 strains of A. baumannii isolated from pus, urine, and other specimens submitted to the Department of Laboratory Medicine of a university hospital, located in Gyeonggi-do, Korea, was investigated over a 3-year period between January 2017 and December 2019. Results: Antimicrobial susceptibility tests on bacteria isolated in clinical practice demonstrated that 26 strains (79%) were MRAB, while multi-locus sequence typing indicated that ST191 was the predominant type (45%; n = 15). Checkerboard test results demonstrated that combination therapy using meropenem and colistin had the highest synergistic effect (fractional inhibitory concentration index = 0.5), while the time-kill assay test using Lactobacillus spp. culture extract exhibited an inhibitory effect within 1 h and complete inhibition of MRAB within 3 h. Lactobacillus paracasei exhibited the fastest antimicrobial reactivity and longest sustained antimicrobial activity. Conclusion: These findings provide useful foundational data for an appropriate combination of colistin with other antimicrobial agents for treating MRAB infection in clinical settings, and the use of various probiotic culture extracts to reduce the required dosage, and therefore toxicity of colistin.

A Quencher-Based Blood Autofluorescence-SuppressionStrategy Enables the Quantification of Trace Analyte in Whole Blood.

Precise quantification of trace components in whole blood via fluorescence is of great significance. However, the applicability of current fluorescent probes in whole blood is largely hindered by the strong blood autofluorescence. Here, we proposed a blood autofluorescence-suppressed sensing strategy to develop an activable fluorescent probe for quantification of trace analyte in whole blood.Based on inner filter effect, by screening fluorophores whose absorption overlapped with the emission of blood, a redshift BODIPYquencher with an absorption wavelength ranging from 600-700 nm was selected for its superior quenching efficiencyand high brightness. Two 7-nitrobenzo[c] [1,2,5] oxadiazole ether groups were introduced onto the BODIPY skeleton for quenching its fluorescence and the response of H2S, a gas signal molecule that can hardly be quantified because of its low concentration in whole blood. Such detection system shows a pretty low background signal and high signal-to-back ratio, the probe thus achieved the accurate quantification of endogenous H2S in 20-fold dilution of whole blood samples, which is the first attempt of quantifying endogenous H2S in whole blood. Moreover, this autofluorescence-suppressed sensing strategy could be expanded to other trace analytes detection in whole blood, which may accelerate the application of fluorescent probes in clinical blood test.

A Quencher‐Based Blood‐Autofluorescence‐Suppression Strategy Enables the Quantification of Trace Analytes in Whole Blood

AbstractPrecise quantification of trace components in whole blood via fluorescence is of great significance. However, the applicability of current fluorescent probes in whole blood is largely hindered by the strong blood autofluorescence. Here, we proposed a blood autofluorescence‐suppressed sensing strategy to develop an activable fluorescent probe for quantification of trace analyte in whole blood. Based on inner filter effect, by screening fluorophores whose absorption overlapped with the emission of blood, a redshift BODIPY quencher with an absorption wavelength ranging from 600–700 nm was selected for its superior quenching efficiency and high brightness. Two 7‐nitrobenzo[c] [1,2,5] oxadiazole ether groups were introduced onto the BODIPY skeleton for quenching its fluorescence and the response of H2S, a gas signal molecule that can hardly be quantified because of its low concentration in whole blood. Such detection system shows a pretty low background signal and high signal‐to‐back ratio, the probe thus achieved the accurate quantification of endogenous H2S in 20‐fold dilution of whole blood samples, which is the first attempt of quantifying endogenous H2S in whole blood. Moreover, this autofluorescence‐suppressed sensing strategy could be expanded to other trace analytes detection in whole blood, which may accelerate the application of fluorescent probes in clinical blood test.

35 Effects of melatonin on inflammatory marker serum amyloid A in horses after exercise

Performance horses are regularly exposed to various stressors, such as training and exercise, that negatively impact their performance which may lead to increased oxidative stress (OS) and inflammation. Although important for the adaptive response, prolonged and unresolved OS and inflammation may decrease athletic performance or cause unnecessary cellular damage. Dietary supplements, such as antioxidants, have been shown to mitigate the negative effects of OS and inflammation and therefore may enhance performance. One such antioxidant that has been of interest is melatonin. The objectives of this study were to evaluate the potential of melatonin to reduce Serum Amyloid A (SAA), a sensitive inflammatory marker, in horses after exercise. Horses (n = 6) were randomly assigned to 2 groups (CON; n = 3, no supplement or MEL; n = 3, 20 g melatonin). Horses received diet based on BW (1% BW Nutrena Impact 12% Pellets and 2% BW bermudagrass hay/d). A switchback design was used, with 2 experimental trial periods lasting 14-d with a 30-d washout period in-between. Supplementation was given orally on exercise days during each trial period. Horses underwent 1.5hr of moderate-intensity exercise (avg >90 BPM), at 0700 3 d/wk. Blood was drawn before exercise (PRE), and at 30- and 90-min post-exercise. On exercise days (ED), horses received supplementation after PRE blood draw and before exercise (0630).After the washout period, the treatment groups were swapped, and the study was repeated, resulting in 12 ED total. Blood was collected via jugular venipuncture, immediately processed to separate plasma, and stored for analysis. SAA ELISA kits (Thermo Fisher Scientific Inc., Massachusetts) were used to determine blood SAA concentration. The first and last ED of each trial period were analyzed (ED1/ED6/ED7/ED12), and interactions of treatment, time, and day were analyzed with significance set at (P ≤ 0.05). PRE ED1 and 7 were set as baseline values, with no significant differences in baseline levels between treatments (P > 0.1862). There was a significant difference between treatments at 30- (P ≤ 0.01) and 90-min (P ≤ 0.01) post-exercise on ED1, 7, and 12, with average plasma SAA concentrations being lower for MEL group at all time points. There was also a treatment*day interaction for ED1 (P = 0.0005), ED7 (P = 0.0218), and ED12 (P = 0.0001), with MEL having lower SAA blood concentrations as compared with CON. Lower concentrations of SAA in MEL horses suggest melatonin supplementation may reduce inflammatory blood markers and, in turn, may suggest lower levels of inflammation in horses after exercise.

Analysis of the correlation between clinical efficacy and blood concentration of olanzapine in schizophrenia patients.

To analyze the relationship between olanzapine blood concentration and clinical efficacy in schizophrenia patients, which has been expected to provide a scientific reference basis for improving the treatment effect of olanzapine in schizophrenia patients. Four hundred eighty-six psychiatric inpatients were randomly selected from October 31, 2019, to October 31, 2020, and all enrolled patients were given olanzapine treatment, and the treatment effect of schizophrenia patients was assessed according to the Positive and Negative Symptom Scale subtraction rate, and divided into treatment effective and ineffective groups at 1, 2, and 3 weeks of treatment, respectively. The olanzapine blood concentration in the body was monitored at 1, 2, and 3 weeks of treatment, and the relationship between olanzapine blood concentration and treatment effect at different time points was analyzed. Patients in the ineffective group had lower olanzapine blood concentrations than the effective group in treatment 1, 2, and 3 weeks and lower Positive and Negative Symptom Scale score reduction rates than the effective group (P < .05); the differences in other baseline information between the groups were not statistically significant (P > .05). Logistic regression analysis showed that olanzapine blood concentration at different times of treatment was related to the treatment effect (odds ratio > 1, P < .05); the results of the bivariate Spearman linear correlation test showed that olanzapine blood concentration at different times of treatment was positively related to the treatment effect of schizophrenia patients (R > 0, P < .05). In schizophrenia patients treated with olanzapine, the higher the olanzapine blood concentration in patients, the better the clinical treatment effect. Accordingly, the clinical can develop individualized medication regimens based on the results of blood concentration testing in the body under the premise of ensuring safety, aiming to ensure maximum efficacy.

Higher Maternal Protein Intake during Pregnancy Is Associated with Lower Cord Blood Concentrations of Insulin-like Growth Factor (IGF)-II, IGF Binding Protein 3, and Insulin, but Not IGF-I, in a Cohort of Women with High Protein Intake

Higher Maternal Protein Intake during Pregnancy Is Associated with Lower Cord Blood Concentrations of Insulin-like Growth Factor (IGF)-II, IGF Binding Protein 3, and Insulin, but Not IGF-I, in a Cohort of Women with High Protein Intake

"I know why I am taking this pill": Young women navigation of disclosure and support for PrEP uptake and adherence in Eastern Cape Province, South Africa.

There is limited understanding of the dynamic interplay between adolescent girl's and young women's (AGYW) disclosure and social support for using oral pre-exposure prophylaxis (PrEP) and adherence. Towards this, we conducted interviews with 42 AGYW enrolled in The Community PrEP Study who exhibited either high or low blood concentrations of tenofovir-diphosphate (TFV-DP) in dried blood spots. Guided by Theories of Practice, interviews and analysis focused on AGYW perspectives and experiences with PrEP disclosure, support and adherence. AGYW with high TFV-DP blood concentrations described larger social support networks and disclosure events. In contrast, those with low TFV-DP blood concentrations described disclosing to fewer people, resulting in limited social support. Participants discussed partner support, however, this support was not described as consequential to adherence, irrespective of TFV-DP levels. Those with high levels of TFV-DP in their blood described the ability to navigate social scrutiny and changes in social support, while those with low levels of TFV-DP in their blood were more likely to question their own continued use of PrEP. To facilitate AGYW's prevention-effective use of PrEP, expanded skill-building for disclosure and resiliency against changes to social support should be examined as part of PrEP services.

Pharmacological Mechanisms and Clinical Applications of Curcumin: Update.

Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. However, the disadvantages of low bioavailability, short half-life in plasma, low drug concentration in blood, and poor oral absorption severely limited the clinical application of curcumin. Pharmaceutical researchers have carried out plenty of dosage form transformations to improve the druggability of curcumin and have achieved remarkable results. Therefore, the objective of this review summarizes the pharmacological research progress, problems in clinical application and the improvement methods of curcumin's druggability. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects. The deficiencies of lower bioavailability of curcumin could be improved by dosage form transformation. However, curcumin in the clinical application still requires further study regarding the underlying mechanism and clinical trial verification.