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Objective To obtain the monitoring measurement range of quality indicators of red blood cells, plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province, explore the distribution of monitoring values and the change of monitoring level, so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei. Methods In 2023, the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected, scatter plots were made and the range markers were set, and the "mean±SD" line was taken as the upper limit and lower limit of the measurement range. In 2024, the monitoring values in 2023 were added, and the changes of two measurement ranges were compared to analyze the stability and overall level. Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin, washed erythrocyte-hemoglobin, washed erythrocyte-supernatant protein, cryoprecipitate coagulation factor-FⅧ, fresh frozen plasma-FⅧ, leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993, 6.252 to 6.104, 0.273 to 0.267, 57.506 to 56.276, 0.920 to 0.892, 0.653 to 0.644 and 2.653 to 2.603, respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced dispersion. Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells, hemoglobin content of the wash erythrocyte, protein content of supernatant of the wash erythrocyte, hemolysis rate of the wash erythrocyte, FⅧ content of the cryoprecipitate coagulation factor, plasma protein content of the fresh frozen plasma, FⅧ content of the fresh frozen plasma, platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476, 44.915 to 44.861, 0.280 to 0.283, 0.137 to 0.142, 133.989 to 133.271, 60.262 to 60.208, 1.301 to 1.277 and 3.036 to 3.033, respectively, and was closer to the national standard line, which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023. The long-term qualified rate of coagulation items was low, and no improvement has been observed. The stability of biochemical items has been enhanced but overall deviation has occurred, with the average value close to the national standard line. The possibility of subsequent testing failure has increased. The counting items showed no obvious common characteristics. Conclusion The use of "mean±SD" in the analysis can visually display the distribution of monitoring values of different items in Hebei, forming an indicator measurement range covering the past nine years. It shows the characteristics of each item, and provides reference for subsequent quality control laboratory data analysis of each blood stations to takes active measures to improve the monitoring level.

This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single‐center, open‐label, two‐period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8‐day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat‐to‐epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration–time curve from time 0 up to 16 h at steady state (AUC0‐16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%‐125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0‐τ,ss, the zamicastat plus epoprostenol‐to‐zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0‐τ,ss and the zamicastat plus epoprostenol‐to‐zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0‐τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant. [ABSTRACT FROM AUTHOR]

Yield stress, τy, is a key rheological property of complex materials such as gels, dense suspensions, and dense emulsions. While there is a range of established techniques to measure τy in the order of tens to thousands of pascals, the measurement of low τy, specifically below 1 Pa, remains underexplored. In this article, we present the measurement of low apparent τy using a Hele-Shaw microfluidic extensional flow device (MEFD). Using the MEFD, we observe a gradient in shear stress, τ, such that τ is lower near the center or stagnation point, and higher away from the stagnation point. For a yield stress fluid, we observe that, below a certain flow rate, τ exceeds τy only in the outer region, leading to stagnation or unyielding of the fluid in the inner region. We use scaling analysis based on a Hele-Shaw linear extensional flow to deduce τy by measuring the size of the unyielded region, S. We validate this scaling relationship using Carbopol solutions with concentrations ranging between 0.015 to 0.3%, measuring τy as low as ∼10 mPa to ∼1 Pa, and comparing it with τy measured using a standard rheometer. While the experimental lower limit of our technique is 5 mPa, modifying the geometry or improving the image analysis can reduce this limit to the order of 10-4 Pa. The MEFD facilitates rapid measurement of τy, allowing for its real-time assessment. We further report τy of human blood samples between 30 to 80 mPa with their hematocrit ranging between 14 to 63%. Additionally, we determine τy for a mucus simulant (∼0.7 Pa), and lactic drink (∼7 mPa) to demonstrate the versatility of the MEFD technique. [ABSTRACT FROM AUTHOR]

Background: Effective testing for malaria, including the detection of infections at very low densities, is vital for the successful elimination of the disease. Unfortunately, existing methods are either inexpensive but poorly sensitive or sensitive but costly. Recent studies have shown that mid-infrared spectroscopy coupled with machine learning (MIRs-ML) has potential for rapidly detecting malaria infections but requires further evaluation on diverse samples representative of natural infections in endemic areas. The aim of this study was, therefore, to demonstrate a simple AI-powered, reagent-free, and user-friendly approach that uses mid-infrared spectra from dried blood spots to accurately detect malaria infections across varying parasite densities and anaemic conditions. Methods: Plasmodium falciparum strains NF54 and FCR3 were cultured and mixed with blood from 70 malaria-free individuals to create various malaria parasitaemia and anaemic conditions. Blood dilutions produced three haematocrit ratios (50%, 25%, 12.5%) and five parasitaemia levels (6%, 0.1%, 0.002%, 0.00003%, 0%). Dried blood spots were prepared on Whatman™ filter papers and scanned using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) for machine-learning analysis. Three classifiers were trained on an 80%/20% split of 4655 spectra: (I) high contrast (6% parasitaemia vs. negative), (II) low contrast (0.00003% vs. negative) and (III) all concentrations (all positive levels vs. negative). The classifiers were validated with unseen datasets to detect malaria at various parasitaemia levels and anaemic conditions. Additionally, these classifiers were tested on samples from a population survey in malaria-endemic villages of southeastern Tanzania. Results: The AI classifiers attained over 90% accuracy in detecting malaria infections as low as one parasite per microlitre of blood, a sensitivity unattainable by conventional RDTs and microscopy. These laboratory-developed classifiers seamlessly transitioned to field applicability, achieving over 80% accuracy in predicting natural P. falciparum infections in blood samples collected during the field survey. Crucially, the performance remained unaffected by various levels of anaemia, a common complication in malaria patients. Conclusion: These findings suggest that the AI-driven mid-infrared spectroscopy approach holds promise as a simplified, sensitive and cost-effective method for malaria screening, consistently performing well despite variations in parasite densities and anaemic conditions. The technique simply involves scanning dried blood spots with a desktop mid-infrared scanner and analysing the spectra using pre-trained AI classifiers, making it readily adaptable to field conditions in low-resource settings. In this study, the approach was successfully adapted to field use, effectively predicting natural malaria infections in blood samples from a population-level survey in Tanzania. With additional field trials and validation, this technique could significantly enhance malaria surveillance and contribute to accelerating malaria elimination efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: The metabolic profile implies simultaneous determination of carbohydrate, fat, protein, and mineral metabolism parameters as well as endocrinological parameters in the blood of cows. Blood is exposed to a variety of preanalytical factors during sampling, transport to the laboratory, and laboratory preparation for analysis, which may cause hemolysis of the sample. As hemolysis affects the values of the metabolic profile, the analyzed blood parameters may falsely increase or decrease, and the metabolic status of the cows may be misinterpreted. Preventing hemolysis is important because severe hemolysis requires discarding the sample and resampling, which is very resource-intensive. In this paper, three levels of hemolysis were determined for each blood parameter tested: (a) a hemolysis level that does not affect the values of the parameters and allows the results to be issued without restriction; (b) a hemolysis level that affects the values of the parameters but remains within the acceptable biological variability and permits the results to be issued along with a note in the form of a correction formula; and (c) a hemolysis level at which the obtained values of the parameters or the entire sample must be discarded. The results are presented graphically using interferograms, which can be easily implemented in every laboratory after validation. Hemolysis is a common cause of errors in laboratory tests as it affects blood parameters and leads to a positive or negative bias. This study aims to examine the relationship between the level of hemolysis (expressed as cell-free hemoglobin concentration, g/L) and the variability of metabolic and endocrine parameters and to determine the threshold level of hemolysis that causes an analytically and clinically significant bias for the twenty most frequently examined blood parameters in cows. Paired blood samples of 10 mL each were obtained from 30 cows. One was subjected to mechanical trauma and plasma was extracted directly from the other. Hemolyzed and non-hemolyzed samples from the same animal were mixed to obtain final samples with cell-free hemoglobin concentrations of 0, 1, 2, 4, 6, 8, and 10 g/L. Metabolic and endocrine parameters were measured in the samples and their deviation and the linear equation between the level of hemolysis and the deviation were determined. The following threshold values of hemolysis were determined, which correspond to the acceptable analytical (lower value) and clinical (upper value) levels of parameter variability: BHB 0.96 and 4.81; NEFA 0.39 and 3.31; GLU 0.38 and 3.90; ALB 1.12 and 6.11; TPROT 1.40 and 6.80; UREA 6.62 and 20.1; TBIL 0.75 and 5.65; AST 0.11 and 2.18; GGT 1.71 and 8.90, LDH 0.01 and 0.11, ALP 0.97 and 2.95; TGC 1.56 and 15.5; CHOL 1.29 and 8.56; Ca 5.68 and 25.7; P 0.57 and 8.43; Mg 1.10 and 8.47; INS 1.15 and 3.89; T3 8.19 and 15.6; T4 8.97 and 18.5; and CORT 2.78 and 11.22 g/L cell-free hemoglobin. Three decision levels are available for each metabolic and endocrine parameter: if hemolysis is below the lower (analytical) threshold value, results can be reported without restriction; if hemolysis is between the lower and upper thresholds, the results can be issued with guidance in the form of corrective linear equations; and if hemolysis is above the upper (clinical) threshold, the results and sample must be discarded. This method contributes to an optimal approach to hemolysis interference with metabolic profile parameters in blood samples from cows. [ABSTRACT FROM AUTHOR]

A pre-transfusion crossmatch test is crucial for ensuring safe blood transfusions by identifying the compatibility between donor and recipient blood samples. Conventional tube methods for crossmatching have limitations, including subjectivity in result interpretation and the potential for human error. In this study, we evaluated the diagnostic performance of a new crossmatch test using Microscanner C3, which can overcome these shortcomings. The crossmatch test results using the method were obtained in 323 clinical samples. The sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of the crossmatch test using Microscanner C3 were 98.20%, 100.00%, 100.00%, 98.11%, and 99.07%, respectively. The diagnostic performance of the new system offers a promising alternative to conventional tube methods for pre-transfusion crossmatch testing. Microscanner C3 could also increase the automation, standardization, and accuracy of crossmatch tests. The crossmatch test using Microscanner C3 is thought to increase the efficiency and reliability in identifying blood samples suitable for transfusion, thereby improving patient safety and optimizing the use of blood products in clinical settings. [ABSTRACT FROM AUTHOR]

In the current study, we examined the association between eveningness and testosterone levels in men. Specifically, we differentiated between free and total testosterone fractions, with free testosterone being recognized as the most bioavailable form of this hormone. We collected blood samples from 298 men aged 18–44 to assess total and free testosterone. Additionally, we measured sleep timing variables using the Munich Chronotype Questionnaire. The main result of the current study indicated that evening chronotype was associated with higher levels of free testosterone, but was unrelated to total testosterone. Sleep loss was unrelated to the both testosterone fractions. We expanded prior findings by utilizing a more comprehensive testosterone assay what indicated that evening chronotype is primarily associated with the most bioavailable form of testosterone (i.e. free testosterone) in adult men. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to assess the outcomes of parathyroid gland reimplantation with PR-FaST technique in patients undergoing thyroid surgery, focusing on graft functionality over a 5-year follow-up period. Materials and Methods: We analyzed data from 131 patients who underwent parathyroid reimplantation using the PR-FaST technique during thyroid surgery due to inadvertent parathyroid removal or evident vascular damage. Postoperative evaluations included serum calcium (Ca), magnesium (Mg), and phosphorus (P) analyses on the 1st and 2nd postoperative days, at 10 days, and at 1, 3, 6 months, 1 year, and 5 years of follow-up. Additionally, the mean values of serum intact parathyroid hormone (iPTH) concentration were measured from blood samples collected from both the reimplanted arm (iPTH RA) and non-reimplanted arm (iPTH NRA) within the same period. Results: Among 131 patients, at 10 days post-surgery, only 46 patients (35.1%) out of 131 exhibited graft viability (iPTH ratio >1.5). This percentage increased to 72.8% (94 patients) after 1 month and further to 87.8% (108 patients) after 3 months post-surgery. At 1 year, 84.7% of patients showed good graft functionality. After 5 years, the percentage remained stable, with graft viability observed in 81.3% of patients. Only 91 of the initial 131 patients completed follow-up up to 5 years, with a dropout rate of 30.5 %. Conclusions: Parathyroid reimplantation using the PR-FaST technique is a viable option for patients undergoing thyroidectomy and has been shown to be a reproducible and effective technique in most patients, with sustained graft functionality and parathyroid hormone production over a 5-year follow-up period. [ABSTRACT FROM AUTHOR]

Tacrolimus is immunosuppressive drugs that have a narrow therapeutic range, and a large inter-patient variability in their pharmacokinetics. Serial monitoring of tacrolimus after transplantation is important to ensure the concentration in biological fluids is maintained at the therapeutic range. Blood sampling for therapeutic drug monitoring of tacrolimus is mostly by venipuncture, making it inconvenient and invasive due to repeated sampling. Thus, microsampling has been adopted as an alternative for sample collection as it is less invasive and more convenient for patients. This article aims to review validated bioanalysis methods for tacrolimus to compare the methods using venous sample and microsampling methods. Related studies about tacrolimus analysis method in blood samples were screened from several databases and summarized with PRISMA flow diagram. A total of 12 studies were considered eligible and reviewed in this article. This systematic review provides a narrative of sample quantification of tacrolimus that collected by venipuncture and microsampling method, its bioanalytical method employed to perform the analysis, and clinical validation or application to patients with organ transplants. Studies with microsampling methods have been validated and applied to the patients. Some studies that compared both methods concluded there is no significant difference between tacrolimus concentrations by venipuncture or microsampling methods. Therefore, microsampling can be considered an option for future development of sampling method in tacrolimus routine monitoring. [ABSTRACT FROM AUTHOR]

The study presents the importance of forensic bacteriology, its use in forensic cases, the methods for bacteriological sampling from corpses, the types and species of bacteria isolated from human and pig corpses, which are most commonly used in forensic biology. The microbial changes that occur after death remain unclear. Postmortem microbiology is a relatively new field of research. After death, the failure of the immune system and other physical barriers leads to the proliferation and spread of microbes. In order for bacteriological information to be accepted within the scope of forensic bacteriology, the court must find suspicion to be present about whether the bacteria seen on the body will contribute to solving the case. Experts must be appointed to examine the issue in line with this suspicion, and these experts must prepare and submit their reports to the court at the requested time. When considering the literature studies, forensic bacteriology has been suggested to be a scientific discipline in the developmental stage and to only be able to provide circumstantial evidence in forensic cases as opposed to primary evidence. According to the literature review, most bacterial studies isolated from corpses were conducted in Romania. Although bacterial samples were isolated from various parts of the corpses, bacteria were mostly isolated from their blood samples. According to literature searches from various scientific journal databases, no study has occurred with a list of the bacteria isolated from corpses. This study is thought to be able to fill this important gap. [ABSTRACT FROM AUTHOR]

An unidentified compound in putrefied postmortem blood samples showed identical accurate mass and chromatographic behavior as 3,4-methylenedioxyamphetamine (MDA) and led to false-positive preliminary screening results. The aim of the study was to identify this unknown interference. Postmortem blood samples were analyzed after protein precipitation on a QExactive Focus high-resolution mass spectrometer (Thermo Fisher, Germany) coupled to a RP C18 column (Macherey-Nagel, Germany). Based on the analysis of mass spectrometry (MS) adducts and isotope ratios using fullscan (m/z 134–330) information, the empiric formula of the protonated molecule [M + H]+ of the unknown compound was found to be C10H14O2N (+ 0.6 ppm). Product ion spectra recorded using normalized collision energy 22% showed a base peak of C8H9O1 (+ 1.5 ppm) and a low-abundant water loss to C7H9 (+ 1.9 ppm), neutral losses of C2H2O and NH3 were found. Based on fullscan and MS-MS information and under consideration of the observed order of neutral losses, the compound was presumptively identified as N -acetyltyramine. This assumption was supported by SIRIUS software showing a SIRIUS score of 99.43% for N -acetyltyramine. Finally, the putative structure annotation was confirmed by a reference compound. The described false-positive MDA findings could be attributed to the presence of N -acetyltyramine in putrefied blood samples. Being an isomer of MDA, N -acetyltyramine could not be distinguished by high-resolution data of the protonated molecules. The presented results once again highlight that false-positive findings may occur even in hyphenated high-resolution mass spectrometry (HRMS) when using full-scan information only. [ABSTRACT FROM AUTHOR]

Simple Summary: Early pregnancy diagnosis is of major importance to the economics of dairy herds. The detection of placental proteins, termed pregnancy-associated glycoproteins (PAGs), represents a diagnostic tool to identify both pregnant and non-pregnant cows. However, as milk production correlates negatively with plasma levels of PAGs during early pregnancy, detection of PAGs may be hindered by high milk production. This study evaluates a newly developed commercial PAGs-based pregnancy test using whole blood or plasma samples during early pregnancy (28–55 days of gestation) in high-producing dairy cows. This study evaluated a commercial pregnancy-associated glycoproteins (PAGs)-based pregnancy test using whole blood or plasma samples during early pregnancy (28–55 days of gestation) in high-producing dairy cows. Transrectal ultrasonography was used as the gold standard method. The study population constituted of 284 cows. False positive diagnoses were recorded from Day 60 to 89 and from Day 60 to 99 postpartum in blood and plasma samples, respectively. In early pregnancy screening, correct positive diagnoses were recorded in 75% and 100% of blood and plasma samples, respectively. High milk production was associated with negative results in blood samples and with the lowest test line intensity in plasma samples. False positive or negative diagnoses were recorded in 0% of both types of samples in cows previously diagnosed as pregnant and showing signs of estrus. In conclusion, the use of plasma was more effective than the use of blood in early pregnancy diagnosis. In cows previously diagnosed as pregnant and showing signs of estrus, both types of samples showed the same results. Because of large individual variations, normal single pregnancies could not be differentiated from twin pregnancies, from pregnancies with a recently dead conceptus, or from pregnancies that experienced subsequent pregnancy loss. [ABSTRACT FROM AUTHOR]

Currently, tandem mass spectrometry-based newborn screening (NBS), which examines targeted biomarkers, is the first approach used for the early detection of maple syrup urine disease (MSUD) in newborns, followed by confirmatory genetic mutation tests. However, these diagnostic approaches have limitations, demanding the development of additional tools for the diagnosis/screening of MUSD. Recently, untargeted metabolomics has been used to explore metabolic profiling and discover the potential biomarkers/pathways of inherited metabolic diseases. Thus, we aimed to discover a distinctive metabolic profile and biomarkers/pathways for MSUD newborns using untargeted metabolomics. Herein, untargeted metabolomics was used to analyze dried blood spot (DBS) samples from 22 MSUD and 22 healthy control newborns. Our data identified 210 altered endogenous metabolites in MSUD newborns and new potential MSUD biomarkers, particularly L-alloisoleucine, methionine, and lysoPI. In addition, the most impacted pathways in MSUD newborns were the ascorbate and aldarate pathways and pentose and glucuronate interconversions, suggesting that oxidative and detoxification events may occur in early life. Our approach leads to the identification of new potential biomarkers/pathways that could be used for the early diagnosis/screening of MSUD newborns but require further validation studies. Our untargeted metabolomics findings have undoubtedly added new insights to our understanding of the pathogenicity of MSUD, which helps us select the appropriate early treatments for better health outcomes. [ABSTRACT FROM AUTHOR]

We investigated the pharmacokinetic pathway of berberine and its metabolites in vitro, in Caco-2 cells, and in human participants following the administration of dihydroberberine (DHB) and micellar berberine (LipoMicel®, LMB) formulations. A pilot trial involving nine healthy volunteers was conducted over a 24 h period; blood samples were collected and subjected to Ultra High-Performance Liquid Chromatography–High Resolution Mass Spectrometry (UHPLC-HRMS) analyses to quantify the concentrations of berberine and its metabolites. Pharmacokinetic correlations indicated that berberrubine and thalifendine follow distinct metabolic pathways. Additionally, jatrorrhizine sulfate appeared to undergo metabolism differently compared to the other sulfated metabolites. Moreover, berberrubine glucuronide likely has a unique metabolic pathway distinct from other glucuronides. The human trial revealed significantly higher blood concentrations of berberine metabolites in participants of the DHB treatment group compared to the LMB treatment group—except for berberrubine glucuronide, which was only detected in the LMB treatment group. Similarly, results from in vitro investigations showed significant differences in berberine metabolite profiles between DHB and LMB. Dihydroberberine, dihydroxy-berberrubine/thalifendine and jatrorrhizine sulfate were detected in LMB-treated cells, but not in DHB-treated cells; thalifendine and jatrorrhizine-glucuronide were detected in DHB-treated cells only. While DHB treatment provided higher blood concentrations of berberine and most berberine metabolites, both in vitro (Caco-2 cells) and in vivo human studies showed that treatment with LMB resulted in a higher proportion of unmetabolized berberine compared to DHB. These findings suggest potential clinical implications that merit further investigation in future large-scale trials. [ABSTRACT FROM AUTHOR]

Introduction: this study was designed to measure ethyl alcohol concentrations in blood samples of different matrices (Li-He plasma, K2-EDTA plasma and serum) with the DRI® method on the ILab Taurus analyzer. The aim of the protocol was to compare the values between the matrices K2-EDTA and serum with Li-He plasma. Furthermore, 18 real samples from the emergency room were used to compare the results obtained with the enzymatic method on both Li-He and K2-EDTA plasma in comparison with the GC/HS reference method. Methods: serum, Li-He and K2-EDTA samples were obtained from left-over routine samples to obtain different pools (serum, Li-He plasma and K2-EDTA plasma pools). Samples with different expected concentrations of ethanol (range 0.00-2.22 g/L) were prepared in situ (60 samples for each matrix) by precise additions of a 10% ethanol solution. All these samples were stored at -20°C until use. Results: in the expected concentration range between 0.42 and 0.85 g/L and around 0.8 and 1.5 g/L [which incorporates most of the legally permitted levels of BAC (Blood Alcohol Concentration) in Europe including Italy] the CV% obtained are all <5.0%. The GC/HS correlation with ILab Taurus for both plasma matrices, LI-He and K2-EDTA evaluated in 18 genuine samples was excellent. Discussion: all the obtained results show that for all the matrices evaluated in the study, the analytical performances are highly satisfactory. [ABSTRACT FROM AUTHOR]

Introduction: Early diagnosis of neonatal sepsis is very essential part of newborn care to prevent mortality and decrease morbidity in newborns. Aim: The aim of this study is to correlate an increase in C‑reactive protein (CRP) titre and a decrease in platelet count with an increased incidence of neonatal septicemia, for an effective subtle approach in neonatal septicemia. Materials and Methods: A retrospective study was conducted in the neonatal intensive care unit (NICU) of a tertiary care hospital from Jan 2022 to July 2023. Neonates admitted to the NICU with suspected sepsis were screened for sepsis. Screening was done by taking blood culture samples before administration of antibiotics, serum samples for CRP and blood samples for platelet count. Result: A total of 270 newborns with suspected sepsis were included in the study. Blood culture positivity was seen in 27.7 (27/75) cases. About 32.9% (89/270) of the neonates with suspected sepsis and 61.3% (46/75) neonates with confirmed sepsis had raised CRP; 32.2% (87/270) neonates with suspected sepsis and 64% (48/75) with confirmed sepsis had decreased platelet count. Both an increase in CRP and a decrease in platelets were seen in 61.3% (46/75) of confirmed cases. Conclusion: In our study, both raised CRP and decreased platelet count were seen in around 60% of confirmed cases of sepsis. So, CRP titre and platelet count can be used as early, rapid diagnostic markers for confirmed sepsis. [ABSTRACT FROM AUTHOR]

The current study examined the levels of antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH), and Malondialdehyde (MDA) and reproductive hormones (progesterone, estrogen, and cortisol) in pregnant local breed ewes and after lambing in the Basrah governorate. Twenty ewes were used in this study from several fields in the Basrah governorate. Blood sample collection was done in three different periods, pre-lambing, immediately after lambing, and two weeks after lambing. The result showed a significant decrease (p<0.05) in SOD, CAT, and GSH-px activity before and during lambing compared to after lambing. The results also confirmed a significant increase (p<0.05) in the level of GSH pre and during lambing compared to after lambing. While evaluating, the level of MDA revealed a significant increase (p<0.05) in its level during lambing compared to two weeks after lambing. Hormonal analysis showed a significant increase (p<0.05) in the levels of cortisol and estradiol pre and during lambing compared to after lambing, with a significant decrease (p<0.05) in the levels of progesterone after lambing compared to before lambing. This study concluded that during lambing, ewes were under stress factors, and an internal mechanism represented by enzymatic antioxidants like SOD, CAT, and GSH-Px acted actively during this period to neutralize the side effects of stress. [ABSTRACT FROM AUTHOR]

Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has a long latency phase before clinical onset, creating a need to identify subclinical disease. We hypothesized circulating transthyretin (TTR) and retinol binding protein 4 (RBP4) levels would be associated with TTR carrier status and correlated with possible evidence of subclinical ATTRv-CA. TTR and RBP4 were measured in blood samples from V122I TTR carriers and age-, sex- and race-matched non-carrier controls (1:2 matching) among Dallas Heart Study participants (phases 1 (DHS-1) and 2 (DHS-2)). Multivariable linear regression models determined factors associated with TTR and RBP4. There were 40 V122I TTR carriers in DHS-1 and 54 V122I TTR carriers in DHS-2. In DHS-1 and DHS-2, TTR was lower in V122I TTR carriers (p <.001 for both), and RBP4 in DHS-2 was lower in V122I TTR carriers than non-carriers (p =.002). Among V122I TTR carriers, TTR was negatively correlated with markers of kidney function, and limb lead voltage (p <.05 for both) and TTR and RBP4 were correlated with atrial volume in DHS-2 (p <.05). V122I TTR carrier status is independently associated with lower TTR and RBP4 in comparison with non-carriers. These findings support the hypothesis that TTR and RBP4 may correlate with evidence of subclinical ATTRv-CA. [ABSTRACT FROM AUTHOR]

1. A reduction in crude protein (CP) in feed for broiler chickens necessitates elevated free amino acid (AA) levels to meet the requirement of each AA. This study investigated adaptations following a change to diets with increasing free AA concentrations and possible reasons for the limitation caused by the inclusion of more free AA. 2. Male Ross 308 broiler hatchlings received a starter diet (164 g CP/kg containing 80 g/kg soy protein isolate (SPI)) until d 7. From d 7–22, birds received a diet almost identical to the starter diet or two other diets, where 50% or 100% of digestible AA in SPI were substituted with a free AA mixture. Birds were allocated to metabolism units located in the same barn to determine performance (n = 7 units) and blood traits (n = 14 birds). Total excreta collection was performed on d 7–8, 8–9, 9–10, 11–12, 14–15 and 21–22. Blood samples were collected on d 7, 8, 9, 11, 14 and 21. 3. Average daily weight gain (ADG) and average daily feed intake (ADFI) was unaffected at 50% AA substitution but decreased at 100% AA substitution on d 7–22 (p ≤ 0.001). The 100% substitution led to a decline in ADG and ADFI consistently on all days (p ≤ 0.037) except on d 11–12. A 50% AA substitution resulted in lower ADFI on d 7–8 and 14–15 (p ≤ 0.032). Nitrogen utilisation efficiency (NUE) was on a level of ~ 0.74 and was only affected by treatment up to d 11–12 (p ≤ 0.008). Concentrations of 10, 9, 8, 10 and 4 plasma free AA were affected on d 8, 9, 11, 14 and 21, respectively (p ≤ 0.037). 4. Following a change to diets containing high levels of free AA, NUE and free AA concentrations in the circulation became more balanced within 3 to 7 d. The results suggested that peptide-bound and free AA did not cause different NUE, particularly 3 and 7 d after the diet change. [ABSTRACT FROM AUTHOR]

The hairy-legged vampire bat, Diphylla ecaudata, is a relatively rare, poorly known, and specialized species that feeds primarily on the blood of birds. We studied a large colony of D. ecaudata rosting with the common hematophagous bats Desmodus rotundus, in a brick house in São Paulo, a large metropolis in southeastern Brazil. The colony size varied from 68 individuals in July 2011 to 21 in February 2014, and females were slightly larger than males. This is the first record of a large group of D. ecaudata sheltering in a man-made structure in Brazil and the first largest group of the species recorded in the country. As a rabies control measure, some animals were subjected to fluorescent antibody and mouse inoculation tests. Blood samples were collected from 24 animals, and the sera were tested for the presence of rabies antibodies using a simplified fluorescent inhibition microtest. No bat tested positive for rabies. Using 0.5 IU/ml as the cut-off, the prevalence of rabies antibodies was 58.8% in D. ecaudata and 83.0% in D. rotundus. The expressive levels of rabies antibodies indicate that the rabies virus actively circulates between the two species. El murciélago vampiro patas peludas, Diphylla ecaudata, es una especie especializada, relativamente rara y poco conocida, que se alimenta principalmente de sangre de aves. Estudiamos una gran colonia de D. ecaudata cohabitando con el murciélago vampiro común Desmodus rotundus en una casa de ladrillos en la ciudad de São Paulo, una gran metrópolis en el sureste de Brasil. El tamaño de la colonia varió de 68 individuos en julio de 2011 a 21 en febrero de 2014, y las hembras fueron ligeramente más numerosas que los machos. Este es el primer registro de un grupo grande de D. ecaudata ocupando una estructura artificial en Brasil y el primer registro de un grupo tan grande de la especie en el país. Como medida de control de la rabia, algunos animales fueron sometidos a pruebas de anticuerpos fluorescentes y de inoculación utilizadas en ratones. Se recolectaron muestras de sangre de 24 animales y los sueros se analizaron para detectar la presencia de anticuerpos contra la rabia mediante una microprueba de inhibición fluorescente simplificada. Ningún murciélago dio positivo por rabia. Utilizando 0,5 UI/ml como punto de corte, la prevalencia de anticuerpos contra la rabia fue del 58,8% en D. ecaudata y del 83,0% en D. rotundus. Los niveles de expresión de anticuerpos contra la rabia indican que el virus de la rabia circula activamente entre las dos especies. [ABSTRACT FROM AUTHOR]

This study was designed to determine the prevalence of autoimmune hypothyroidism (Hashimoto's) and its impact on men and women in Thi-Qar Governorat. The current study included (100) people who were in two groups, with (50) people in each group. The first group includes patients with hypothyroidism (Hashimoto's), and the second group includes (Healthy) people who do not suffer from any thyroid disease. Blood samples were collected for the period from (January 1 to March 30/ 2023), for use in measuring the level of thyroid hormones and measuring the level of autoantibodies. The results of the current study showed that female patients had the highest incidence of autoimmune hypothyroidism (Hashimoto’s), at a rate of (68%), while for males, the incidence rate was (32%). As for the age group, the highest incidence rate was for ages over 40 years, and in both cases of the disease The results also showed a relationship between (Sex, Family History, Smoking) and the risk of developing autoimmune hypothyroidism (Hashimoto’s). The results of the current study also showed an increase in the average concentration of thyroid-stimulating hormone (TSH) in patients with hypothyroidism (Hashimoto’s), corresponding to a decrease in the average concentration of each of the hormones (T3, T4, FT4) compared to the healthy group. An increase in the level of autoantibodies (AntiTPOAb, Anti-TgAb) was also observed in patients compared to healthy people. [ABSTRACT FROM AUTHOR]

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Aims: The aim of this study was to identify septicemia in intensive care unit (ICU) patients, determine the antibiotic resistance profiles and minimum inhibitory concentrations (MICs) of all isolates by using the Vitek-2 compact system and study some immunological parameters (IgM, IgG and hs-CRP) in ICU patients, with and without septicemia. Methodology and results: Ninety blood samples from both sexes and different age groups (ranging from 21-90 years) were collected from different hospitals in Mosul city. Twenty-four blood samples were collected from healthy people and used as a control group for the period between July and December of 2022. Samples were subjected to bacterial diagnosis, antibiotic sensitivity test using Vitek2 and measurement of some immunological parameters. The results showed that 24/90 (26.67%) of the blood samples exhibited positive cultures, with Gram-positive bacteria predominating, 14/24 (58.34%), while Gram-negative bacteria represented 10/24 (41.66%) of the positive samples. Antimicrobial susceptibility testing showed that vancomycin, linezolid, imipenem, and rifampicin were mostly effective against most Gram-positive septicemia isolates, whereas meropenem, imipenem and colistin were mostly effective against most Gram-negative bacterial isolates. The ELISA results revealed elevated levels of IgM, IgG and hs-CRP in the serum of septicemia patients compared to the healthy control group, with a significant difference in P-value (0.001). In addition, the mean levels of IgM, IgG and hs-CRP in the serum of non-septicemia patients compared to the healthy control group indicated a highly significant difference in P-value (0.001). Conclusion, significance and impact of study: IgM, IgG and hs-CRP levels were significantly different in sepsis patients infected with Gram-positive and Gram-negative bacteria compared to the healthy control group. [ABSTRACT FROM AUTHOR]

As the beef industry moves towards efficient animal production to improve sustainability in agriculture, new production and management approaches are emerging. Among the many facets of the beef industry, cow–calf operations have the most opportunity for efficiency improvement, including improvements in fertility. This project accounts for measures and methods of (1) twinning reproductive technologies and (2) twin calf perinatal care and pre-weaning rearing. The overall objective was to produce twin calves using two reproductive technologies—embryo transfer and artificial insemination. The subobjectives were to determine accuracy of twin pregnancies embryo/fetal losses using ultrasonography, evaluate parturition and dystocia, and determine the effects of different twin-raising methods on neonatal behavior and growth. A fixed-time artificial insemination (FTAI) protocol was applied to 77 multiparous Angus-cross cows from a commercial beef herd in northcentral South Dakota during the summer of 2019. Cows were assigned to two different treatments groups: only artificially inseminated (AI) or received an embryo transfer following artificial insemination (ET + AI). They were estrous-synchronized, artificially inseminated (AI) with black Angus semen at day 0, and received and embryo transfer (ET) at day 7. Ultrasound examination detected 56% pregnancy risk for both groups, with sensitivity, specificity, and accuracy of 75%, 100%, and 90.5%, respectively, for bilateral twin detection. Calves were born during spring 2020. Twin calves (n = 34) and singleton calves (n = 11) were assigned to one of three raising methods: (1) twin born and twin raised (TT; n = 16), (2) twin born and single raised (TS; n = 18), and (3) single born and single raised (S; n = 11). Neonatal nursing behavior and birth weights were recorded, and adjusted day 200 and day 280 were calculated measures of vitality and growth. Blood samples were collected at age 24 h for colostrum intake measures (total serum protein, IgG1, and IgM). Twin calves were born 20% (p < 0.05) lighter in body weight than singletons; however, weights did not differ at day 280 between TT and S calves. TS calves had the shortest average latency to stand, but immunoglobulin concentrations did not differ among treatments. At weaning, cows that had birthed and raised twins produced more kilograms of live weight per pregnancy than cows birthing and raising singletons. Using ET + AI proved to increase twinning rate, and growth was maintained when raising both twins with their dam. [ABSTRACT FROM AUTHOR]

Kisspeptin is a neuropeptide that governs the reproductive axis upstream to GnRH. Present study was undertaken to compare the effect of different doses of kisspeptin on release of luteinizing hormone (LH) in Murrah buffaloes during pre-pubertal period. Twenty four pre-pubertal buffalo heifers were selected and divided into 4 groups (Control, T1, T2 and T3), having 6 animals in each group. Kisspeptin-10 was administered at the dose of 2 µg/kg body weight, 1.5 µg/ kg body weight, 1µg/kg body weight respectively in T1, T2 and T3 group along with administration of equal volume of NSS in control group. Blood sampling was done at every 20 minutes interval beginning with zero minutes up to 2 hours and analyzed for LH concentration. Results indicated that LH concentration was significantly (p<0.05) higher in T1 group. The peak level of LH was recorded at 20 minutes post administration and falls to basal level at 60 minutes post administration. Although increased LH concentration was observed in other treatment groups but it was lower than T1 group. No LH peak or rise in LH level was observed in control group. The result of this study indicates that during the pre-pubertal period, administration of Kisspeptin causes dose dependent increase in LH concentration and peak level was seen at 2 µg/kg body weight of dose. [ABSTRACT FROM AUTHOR]

Sexual abuse and rape are among the crimes that are increasing day by day in our country. According to 2019 TUIK data, 13.1% of children brought to security units are victimized by sexual crimes. According to data published by the World Population Review website in 2020, 1071 people were raped in Türkiye that year. The provability of crimes is a very important factor for the perpetrator to be punished. The field of forensic sciences tries to serve justice by examining the evidence found at the crime scene. In cases where the possible body fluids of the perpetrator and the victim are mixed, it is very difficult to make an identification because there is no method for the separation of these mixed samples. In this study, we aimed to differentiate mixed body fluids (blood and saliva) by microRNA method. The samples collected from volunteers for this study were prepared as two-donor mixtures in four different groups in five different dilutions. A total of 36 mixtures were prepared from fluids collected from 4 female and 4 male individuals. The miR-451A biomarker was used to indicate the presence of blood and the miR-203A-3p marker was used to indicate the presence of saliva in the mixture samples. The samples were first centrifuged and then RNA isolation was performed using miRNeasy Mini Kit. The concentration and purity of the obtained RNAs were determined by spectrophotometer. Then cDNA (complementary DNA) was synthesized from RNAs with Taqman microRNA Reverse Transcription Kit.U6 gene region was preferred as the reference gene and analyzes were performed by RT-PCR. The presence of blood samples in the mixture was shown in all dilutions, the best level was seen in 1x1 ratio. When all groups were analyzed, it was seen that the mixtures with male donors were expressed at a higher rate than the other mixtures. [ABSTRACT FROM AUTHOR]

Background: Home blood self-collection devices can enable remote monitoring, but their implementation requires validation. Our objectives were to explore (i) the impact of sampling sites and topical analgesia on capillary blood volume and pain perception and (ii) the safety, acceptability, and failure of capillary self-collection among adults and children using the Tasso-SST device. Methods: We conducted a two-phase study. The investigational phase consisted of two on-site cross-sectional studies in healthy adult participants (≥ 12 years) and children (1–17 years) with their accompanying parent. Adults received 4 capillary samplings, where puncture sites and topical analgesia were randomized in a factorial design, and a venipuncture; children (and one parent) had one capillary sampling. The two co-primary outcomes were blood volume and pain. The implementation phase was conducted in two multicentre trials in participants choosing remote visits; blood volume, collection failure, adverse events, and satisfaction were documented. Results: In the investigational phase, 90 participants and 9 children with 7 parents were enrolled; 15 adults and 2 preschoolers participated in the implementation phase. In the adult investigational study, the device collected a median (25%, 75%) of 450 (250, 550) μl of blood with no significant difference between the puncture site, topical analgesia, and its interaction. Using topical analgesia reduced pain perception by 0.61 (95% CI: 0.97, 0.24; P <0.01) points on the 11-point scale; the pain reduction varied by puncture site, with the lower back showing the most significant decrease. Overall, combining all studies and phases, the median volume collected was 425 (250, 500) μl, and the device failure rate was 4.4%; minor adverse effects were reported in 8.9% of the participants, all were willing to use the device again. Conclusion: Capillary blood self-collection, yielding slightly less than 500 μl, proves to be a safe and relatively painless method for adults and children, with high satisfaction and low failure rates. The puncture site and topical analgesia do not affect blood volume, but topical analgesia on the lower back could reduce pain. [ABSTRACT FROM AUTHOR]

Cell-free DNA (cfDNA), a burgeoning class of molecular biomarkers, has been extensively studied across a variety of biomedical fields. As a key component of liquid biopsy, cfDNA testing is gaining prominence in disease detection and management due to the convenience of sample collection and the abundant wealth of genetic information it provides. However, the broader clinical application of cfDNA is currently impeded by a lack of standardization in the preanalytical procedures for cfDNA analysis. A number of fundamental challenges, including the selection of appropriate preanalytical procedures, prevention of short cfDNA fragment loss, and the validation of various cfDNA measurement methods, remain unaddressed. These existing hurdles lead to difficulties in comparing results and ensuring repeatability, thereby undermining the reliability of cfDNA analysis in clinical settings. This review discusses the crucial preanalytical factors that influence cfDNA analysis outcomes, including sample collection, transportation, temporary storage, processing, extraction, quality control, and long-term storage. The review provides clarification on achievable consensus and offers an analysis of the current issues with the goal of standardizing preanalytical procedures for cfDNA analysis. [ABSTRACT FROM AUTHOR]

This study investigates how missing data samples in continuous blood glucose data affect the prediction of postprandial hypoglycemia, which is crucial for diabetes management. We analyzed the impact of missing samples at different times before meals using two datasets: virtual patient data and real patient data. The study uses six commonly used machine learning models under varying conditions of missing samples, including custom and random patterns reflective of device failures and arbitrary data loss, with different levels of data removal before mealtimes. Additionally, the study explored different interpolation techniques to counter the effects of missing data samples. The research shows that missing samples generally reduce the model performance, but random forest is more robust to missing samples. The study concludes that the adverse effects of missing samples can be mitigated by leveraging complementary and informative non-point features. Consequently, our research highlights the importance of strategically handling missing data, selecting appropriate machine learning models, and considering feature types to enhance the performance of postprandial hypoglycemia predictions, thereby improving diabetes management. [ABSTRACT FROM AUTHOR]

Conventional venipuncture is invasive and challenging in low and middle‐income countries. Conversely, point‐of‐care devices paired with fingersticks, although less invasive, suffer from high variability and low blood volume collection. Recently approved microsampling devices address some of these issues but remain cost‐prohibitive for resource‐limited settings. In this work, a cost‐effective microsampling device is described for the collection of liquid blood with minimal invasiveness and sufficient volume retrieval for laboratory analyses or immediate point‐of‐care testing. Inspired by the anatomy of sanguivorous leeches, the single‐use device features a storage compartment for blood collection and a microneedle patch hidden within a suction cup. Finite Element Method simulations, corroborated by mechanical analyses, guide the material selection for device fabrication and design optimization. In piglets, the device successfully collects ≈195 µL of blood with minimal invasiveness. Additionally, a tailor‐made lid and adapter enable safe fluid transportation and integration with commercially available point‐of‐care systems for on‐site analyses, respectively. Taken together, the proposed platform holds significant promise for enhancing healthcare in the pediatric population by improving patient compliance and reducing the risk of needlestick injuries through concealed microneedles. Most importantly, given its cost‐effective fabrication, the open‐source microsampling device may have a meaningful impact in resource‐limited healthcare settings. [ABSTRACT FROM AUTHOR]

Opioid misuse in the United States contributes to >70% of annual overdose deaths. To develop additional therapeutics that may prevent opioid misuse, further studies on the neurobiological consequences of opioid exposure are needed. Here we sought to characterize molecular neuroadaptations involving microRNA (miRNA) pathways in the brain and blood of adult male rats that selfadministered the opioid heroin. miRNAs are -18-24 nucleotide RNAs that regulate protein expression by preventing mRNA translation into proteins. Manipulation of miRNAs and their downstream pathways can critically regulate drug seeking behavior. We performed small-RNA sequencing of miRNAs and proteomics profiling on tissue from the orbitofrontal cortex (OFC), a brain region associated with heroin seeking, following 2 days of forced abstinence from self-administration of 0.03mg/kg/infusion heroin or sucrose. Heroin self-administration resulted in a robust shift of the OFC miRNA profile, regulating 77 miRNAs, while sucrose self-administration only regulated 9 miRNAs that did not overlap with the heroin-induced profile. Conversely, proteomics revealed dual regulation of seven proteins by both heroin and sucrose in the OFC. Pathway analysis determined that heroinassociated miRNA pathways are predicted to target genes associated with the term "prion disease," a termthat was also enriched in the heroin-induced protein expression dataset. Lastly, we confirmed that a subset of heroin-induced miRNA expression changes in the OFC are regulated in peripheral serum and correlate with heroin infusions. These findings demonstrate that peripheral blood samples may have biomarker utility for assessment of drug-induced miRNA pathway alterations that occur in the brain following chronic drug exposure. [ABSTRACT FROM AUTHOR]

Avian haemosporidian parasites are useful model organisms to study the ecology and evolution of parasite-host interactions due to their global distribution and extensive biodiversity. Detection of these parasites has evolved from microscopic examination to PCR-based methods, with the mitochondrial cytochrome b gene serving as barcoding region. However, standard PCR protocols used for screening and identification purposes have limitations in detecting mixed infections and generating phylogenetically informative data due to short amplicon lengths. To address these issues, we developed a novel genusspecific nested PCR protocol targeting avian haemosporidian parasites. The protocol underwent rigorous testing utilizing a large dataset comprising blood samples from Malagasy birds of three distinct Passeriformes families. Furthermore, validation was done by examining smaller datasets in two other laboratories employing divergent master mixes and different bird species. Comparative analyses were conducted between the outcomes of the novel PCR protocol and those obtained through the widely used standard nested PCR method. The novel protocol enables specific identification of Plasmodium, Haemoproteus (Parahaemoproteus), and Leucocytozoon parasites. The analyses demonstrated comparable sensitivity to the standard nested PCR with notable improvements in detecting mixed infections. In addition, phylogenetic resolution is improved by amplification of longer fragments, leading to a better understanding of the haemosporidian biodiversity and evolution. Overall, the novel protocol represents a valuable addition to avian haemosporidian detection methodologies, facilitating comprehensive studies on parasite ecology, epidemiology, and evolution. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation. Methods: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis. Conclusions: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis. [ABSTRACT FROM AUTHOR]

Background: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013–2019) was characterized. Methods: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13—a molecular marker of artemisinin resistance. Result: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. Conclusion: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance. [ABSTRACT FROM AUTHOR]

Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological and behavioral outcomes. This systematic review summarizes the studies investigating the relationship between blood serotonin (5-HT) levels and ASD, comparing diagnostic tools, analytical methods, and clinical outcomes. A literature search on peripheral 5-HT levels and ASD was conducted. In total, 1104 publications were screened, of which 113 entered the present systematic review. Of these, 59 articles reported hyperserotonemia in subjects with ASD, and 26 presented correlations between 5-HT levels and ASD-core clinical outcomes. The 5-HT levels are increased in about half, and correlations between hyperserotonemia and clinical outcomes are detected in a quarter of the studies. The present research highlights a large amount of heterogeneity in this field, ranging from the characterization of ASD and control groups to diagnostic and clinical assessments, from blood sampling procedures to analytical methods, allowing us to delineate critical topics for future studies. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the estrous cycle length of the Algerian Arbia goat in Northern Algeria. For this, eighteen (18) Arbia goats, aged between 2 and 6 years, were used in our work that took place in the experimental farm of the Saad Dahlab University (Blida, Algeria). Blood samples were taken from each goat twice a week (at a 2 or 3-day interval) for 3 months. The serum progesterone concentration was determined by Radio-Immuno-Assay. Smears of the vaginal mucosa were taken at the same time as the blood samples. The predominance of superficial cells on the smear of the vaginal mucosa as well as a serum progesterone level less than 1 ng/mL expressed the return to estrous which was considered the beginning of a new cycle. A negative correlation was observed between the percentage of superficial cells (SC) and serum progesterone (P4) levels in all goats. Our results showed a significant difference (P<0.05) between the means of different cycle lengths obtained among the females. In addition, normal cycles had an average of 20.11±1.85 days (17-25 days) representing 59.6% of cycles. Besides, a large number of short cycles (<17 days) with an average of 14.41±1.51 days were found representing 25.5% of recorded cycles. The number of long cycles (>25 days; with an average of 32.14±5.58 days), represented 14.9% of recorded cycles. Following these results, it can be concluded that the local goat in Northern Algeria had different types of cycles (normal, short, and long) with a large percentage of normal cycles. [ABSTRACT FROM AUTHOR]

The Kerinci duck (Anas platyrhynchos), hailing from Jambi Province, represents one of the local duck breeds of Indonesia. This study aimed to ascertain the matrilineal origin of Kerinci ducks through analysis of the mitochondrial NADH Dehydrogenase subunit 2 (MT-ND2) gene. In this pursuit, forward sequences of the MT-ND2 gene (490 bp) were extracted from unsexed Kerinci ducks, totalling forty-eight (48) sequences, procured from blood samples. The findings demonstrated the identification of fifteen (15) distinct haplotypes within the MTND2 gene, with corresponding haplotype diversity (Hd) and nucleotide diversity (pi) values of 0.74 and 0.003, respectively. The resulting phylogenetic tree unveiled that Kerinci ducks exhibit two matrilineal origins: an Asian and an independent Kerinci lineage. Moreover, most Kerinci ducks were categorised within the H4 group (24 birds) of the Asian lineage. Nevertheless, this study also revealed the existence of an independent Kerinci lineage comprising eight (8) duck haplotypes. In conclusion, the analysis of the MT-ND2 gene underscored the genetic introgression of A. zonorhyncha and A. poecilorhyncha in Kerinci ducks. [ABSTRACT FROM AUTHOR]

Recurrent genetic abnormalities affecting pivotal signaling pathways are the hallmark of childhood acute lymphoblastic leukemia (ALL). The identification of these aberrations remains clinically important. Therefore, we sought to determine the cytogenetic profile and the mutational status of TP53 and RAS genes among Moroccan childhood cases of ALL. In total, 35 patients with childhood ALL were enrolled in the study. The diagnosis and treatment were established in the Pediatric Hematology and Oncology Center at the Children's Hospital of Rabat. Chromosome banding analysis and fluorescence in situ hybridization were used to detect genetic aberrations. Blood samples were screened for TP53 and RAS mutations using Sanger sequencing. Of the 35 cases, 30 were B-lineage ALL (85.7 %). Moreover, a male predominance was observed. Cytogenetic analysis revealed chromosomal anomalies in 27 cases (77.1 %). The most frequent aberrations were high hyperdiploidy and BCR/ABL rearrangement. Interestingly, we found the rare t(15;16) and the t(8;14), which are uncommon translocations in pediatric B-ALL. The mutational analysis revealed Pro72Arg (rs1042522:C > G) and Arg213Arg (rs1800372: A > G) in TP53. In correlation with cytogenetic data, rs1042522:C > G showed a significant association with the occurrence of chromosomal translocations (p = 0.04). However, no variant was detected in NRAS and KRAS genes. Our findings emphasize the significance of detecting chromosomal abnormalities as relevant prognostic markers. We also suggest a low occurrence of genetic variants among Moroccan children with ALL. [ABSTRACT FROM AUTHOR]

Background/aim: The aim of this study was to investigate the effect of phototherapy treatment on serum melatonin levels in term newborn infants. Material and methods: This study was planned as a single-center, prospective, observational, case-control study. Term infants (gestation week ≥37 weeks) who received at least 6 h of phototherapy due to jaundice constitute the phototherapy group, while the term infants without jaundice and who were exclusively breastfed constitute the control group. Melatonin levels were examined by taking blood samples from babies in both groups at 02:00 at night. Melatonin values were compared between groups. The effect of phototherapy on serum melatonin levels was investigated. The relationship between the duration of phototherapy and maximum serum bilirubin values on melatonin values was investigated. Results: Seventy term infants (64.3% girls) were included in the study. Mean gestational week was 38.3 ± 1.1 weeks, mean birth weight was 3295 ± 434 g. There was no statistically significant difference between the phototherapy group and the control group in terms of sex, type of delivery, gestational week, birth weight, height, and head circumference (all p > 0.05). Serum melatonin level was 20.3 ± 5.9 pg/mL (range: 8.7–36.6 pg/mL) in the phototherapy group and 19.9 ± 4.38 pg/mL (range: 9.9–26.3 pg/mL) in the control group. There was no significant difference between the two groups in terms of serum melatonin levels (p = 0.155). The mean total bilirubin value was 17.65 ± 1.48 mg/dL, and the average duration of phototherapy application was 13.94 ± 7.64 h in the babies in the phototherapy group. No correlation was found between the duration of phototherapy application and serum melatonin levels (p = 0.791). Conclusion: It was determined that there was no significant difference in serum melatonin levels in term newborn babies who received phototherapy for at least 6 h due to jaundice. No correlation was found between the duration of phototherapy application and the serum melatonin level of the maximum bilirubin values. [ABSTRACT FROM AUTHOR]

Background: The study of blood trauma, such as hemolysis in blood‐carrying devices, is crucial due to the high incidence of adverse events like alteration of blood function, bleeding, and multi‐organ failure. The extent of flow‐induced hemolysis, predominantly influenced by stress duration and intensity, is described by established model parameters based on the power law approach. In recent years, various parameters were determined using different Couette shearing devices and donor species. However, they have not been validated due to limited experimental data. Methods: This study provides hemolysis measurements in a Couette shearing device and evaluates the suitability of different power law parameters. The revised Couette shearing device generates well‐defined dynamic stress loads that are repeatedly applied to blood samples at a defined temperature. Human blood samples with an adjusted hematocrit of 30%, were tested with varying repetitions (20 to 80 times). The half‐sinusoidal stress loads had amplitudes of 73 to 140 Pa and exposure times of 24 msec per repetition. The parameters of five common power law hemolysis approaches were then compared with the experimental data. Results: The prediction with the power law model parameters C = 3.458 × 10−6, α = 0.2777 and β = 2.0639 showed a good agreement with the experimental results. Conclusion: The effect of multiple short‐time stresses on hemolysis was investigated to validate the power law hemolysis model with the Couette shearing device of this study. [ABSTRACT FROM AUTHOR]

Clopidogrel (CLO), a pro-drug for preventing thrombotic events, undergoes rapid absorption and extensive metabolism, with approximately 85–90% converted to an inactive carboxylic acid metabolite (CLO-CA) and the remaining to an active thiol (CLO-TH). Few pharmacokinetic models for the drug and its metabolites exist, with most focusing on CLO-TH. Although CLO-CA is inactive, its predominant (compared to its parent drug and metabolites) presence in plasma underscores the importance of characterizing its formation and pharmacokinetic profile. This study aimed to characterize the process of the absorption of CLO and its conversion to CLO-CA via developing a population pharmacokinetic model. Individual participants' data from two bioequivalence studies were utilized. Extensive blood samples were collected at predetermined intervals, including 841 concentrations of CLO and 1149 of CLO-CA. A nonlinear, mixed-effects modelling approach using NONMEM® software (v 7.5) was applied. A one-compartment model was chosen for CLO, while a two-compartment proved optimal for CLO-CA. Absorption from the depot compartment was modeled via two transit compartments, incorporating transit rate constants (Ktr). A semi-physiological model explained the first-pass effect of CLO, integrating a liver compartment. The estimated mean transit times (MTTs) for the studies were 0.470 and 0.410 h, respectively. The relative bioavailability for each study's generic medicine compared to the reference were 1.08 and 0.960, respectively. Based on the estimated parameters, the fractions metabolized to inactive metabolites (FiaM_st1 and FiaM_st2) were determined to be 87.27% and 86.87% for the two studies, respectively. The appropriateness of the final model was confirmed. Our model offers a robust framework for elucidating the pharmacokinetic profiles of CLO and CLO-CA. [ABSTRACT FROM AUTHOR]

Expanded CAG repeats in coding regions of different genes are the most common cause of dominantly inherited spinocerebellar ataxias (SCAs). These repeats are unstable through the germline, and larger repeats lead to earlier onset. We measured somatic expansion in blood samples collected from 30 SCA1, 50 SCA2, 74 SCA3, and 30 SCA7 individuals over a mean interval of 8.5 years, along with postmortem tissues and fetal tissues from SCA1, SCA3, and SCA7 individuals to examine somatic expansion at different stages of life. We showed that somatic mosaicism in the blood increases over time. Expansion levels are significantly different among SCAs and correlate with CAG repeat lengths. The level of expansion is greater in individuals with SCA7 who manifest disease compared to that of those who do not yet display symptoms. Brain tissues from SCA individuals have larger expansions compared to the blood. The cerebellum has the lowest mosaicism among the studied brain regions, along with a high expression of ATXN s and DNA repair genes. This was the opposite in cortices, with the highest mosaicism and lower expression of ATXN s and DNA repair genes. Fetal cortices did not show repeat instability. This study shows that CAG repeats are increasingly unstable during life in the blood and the brain of SCA individuals, with gene- and tissue-specific patterns. Large repeated sequences can cause spinocerebellar ataxias (SCAs). They expand in size over time in the blood and the brain, and this instability varies between SCAs and brain regions. This research helps us understand how these genetic changes evolve throughout a person's life, providing insights for future therapeutic strategies. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate and compare the pharmacokinetic parameters of SC ceftazidime administered at 20 and 40 mg/kg to red-eared sliders. ANIMALS 8 adult red-eared sliders (Trachemys scripta elegans). METHODS In a sequential, 2-period study with a 3-week washout period between treatments, ceftazidime was administered SC to turtles at 20 and 40 mg/kg. Blood samples were collected from the subcarapacial sinus at 0, 24, 48, 72, 96, and 120 hours after ceftazidime administration. Plasma ceftazidime concentrations were quantified using reversedphase HPLC. RESULTS Mean plasma half-life after 20- and 40-mg/kg dosing was 39.75 ± 8.0 hours and 33.03 ± 6.56 hours, respectively. Mean maximum plasma concentration after 20- and 40-mg/kg dosing was 71.0 ± 15.93 µg/mL and 120.0 ± 30.62 µg/mL, respectively. Mean plasma ceftazidime concentrations remained ≥ 8 µg/mL, the theoretical MIC for various reptile pathogens for all time points. CLINICAL RELEVANCE Results indicate that ceftazidime dosed at either 20 or 40 mg/kg produces plasma concentrations exceeding the theoretical MIC of various reptile pathogens for at least 120 hours. An ideal dosing interval could not be determined, as all plasma concentrations remained above the threshold of interest for all time points. Follow-up studies should focus on establishing a dosing interval and more rigorous monitoring for potential adverse effects. [ABSTRACT FROM AUTHOR]

Objectives: Disturbed sleep, common during the climacteric, is associated with increased sympathetic activity, a cardiovascular risk factor. We evaluated sleep disturbance effect on autonomic nervous function in climacteric women Methods: Seventeen perimenopausal and 18 postmenopausal women underwent a sleep study protocol: an adaptation night, a reference night, and a sleep disturbance night, with a hand loosely tied to the bed to allow blood sampling. This procedure was repeated after six months of menopausal hormone therapy (MHT) or placebo. Sleep disturbance and MHT effects on overnight heart rate variability (HRV) were analyzed. Results: At baseline, sleep disturbance increased vagal HRV in postmenopausal women, but no changes were seen in perimenopausal women. At six months, sleep disturbance increased total HRV power in the perimenopausal placebo group, and increased nonlinear vagal HRV in the postmenopausal placebo group, but no other changes were seen. MHT did not have any effects on HRV, neither at perimenopause nor at postmenopause. Conclusions: External sleep disturbance had only minor effects on HRV across menopause. MHT had no detectable HRV effects [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the relationship between the atherogenic index of plasma (AIP) and plasma asprosin and metrnl levels in hemodialysis (HD) patients. Methods: Forty-eight patients receiving HD treatment with a diagnosis of end-stage renal disease (ESRD) were included. The control group comprised 34 age-, sex-, and body mass index-matched healthy volunteers without a history of renal disease. ESRD patients were divided into two groups: high-risk (AIP≥0.24) and low-moderate risk (AIP<0.24). Asprosin and metrnl levels in the plasma of blood samples taken just before dialysis were studied by enzyme-linked immunosorbent assay. Results: A significant difference was found between the control group [23.3(19.9-27.7 ng/mL)], the low-moderate risk group [39.3(34.9-40.8 ng/mL)], and the high-risk group [48.1(44.5-49.9 ng/mL)] in terms of asprosin levels (for each p<0.001). Asprosin values of both low-moderate risk and high-risk groups were significantly higher than the controls. In the high-risk group, plasma asprosin levels were higher than in the low-moderate risk group (p=0.012). Metrnl levels of the high-risk group were found to be lower than both the control and low-risk groups (p<0.001 and p=0.003, respectively). AIP showed a positive relation to asprosin and a negative relation to metrnl. Conclusion: Logistic regression analysis has revealed important insights into the independent relationships between metrnl, asprosin, and high AIP values in HD patients. These findings support the anti-atherogenic potential of metrnl and suggest the potential atherogenic effects of asprosin, highlighting the complex interplay between adipokines and cardiovascular risk in this patient population. [ABSTRACT FROM AUTHOR]

Aging is a complex process influenced by genetic, epigenetic, and environmental factors that lead to tissue deterioration and frailty. Epigenetic mechanisms, such as DNA methylation, play a significant role in gene expression regulation and aging. This study presents a new age estimation model developed for the Turkish population using blood samples. Eight CpG sites in loci TOM1L1, ELOVL2, ASPA, FHL2, C1orf132, CCDC102B, cg07082267, and RASSF5 were selected based on their correlation with age. Methylation patterns of these sites were analyzed in blood samples from 100 volunteers, grouped into age categories (20-35, 36–55, and ≥56). Sensitivity analysis indicated a reliable performance with DNA inputs ≥1 ng. Statistical modeling, utilizing Multiple Linear Regression, underscores the reliability of the primary 6-CpG model, excluding cg07082267 and TOM1L1. This model demonstrates strong correlations with chronological age (r= 0.941) and explains 88% of the age variance with low error rates (MAE = 4.07, RMSE = 5.73 years). Validation procedures, including a trainingtest split and fivefold cross-validation, consistently confirm the model's accuracy and consistency. The study indicates minimal variation in error scores across age cohorts and no significant gender differences. The developed model showed strong predictive accuracy, with the ability to estimate age within certain prediction intervals. This study contributes to the age prediction by using DNA methylation patterns, which can have disparate applications, including forensic and clinical assessments. [ABSTRACT FROM AUTHOR]

Objective. Determine chromosomal aberrations such as aneuploidies/polyploidies (ap/pp) of cows with a history of abortion from a municipality in Zacatecas, Mexico. Materials and methods. 107 blood samples were collected from cows with a history of abortion and ages between 3 and 10 years in the municipality of Enrique Estrada Zacatecas Mexico, a chromosomal analysis was performed with the conventional cytogenetic technique, to determine chromosomal aberrations such as aneuploidies/ polyploidies. Results. The ap/pp cows range from those that did not present any aberrations (0%), a median of (2%) and a maximum of (16%) chromosomal aberrations, the recorded age of the cows was a minimum of 3.5 years, a median of 5.8 and a maximum of 7.4. With these results it can be predicted that there is the possibility that with each year a cow will abort and it increases by 31.7%. However, the p of this coefficient is 0.384—not significant. On the other hand, the possibility of a cow aborting increases by 16.5% with each unit percentage increase in the degree of polyploidy, and the p for this coefficient is 0.029, which is significant. Conclusions. Aneuploidies/polyploidies in correlation with the age of the cows are a possible probability of abortion. [ABSTRACT FROM AUTHOR]

Background: Thromboelastogram testing is increasingly being used to manage patients with massive bleeding. An earlier study found that the test results were influenced by the hematocrit (Hct) and platelet (PLT) concentrations. This study sought to determine if these factors confounded the results of a different manufacturer's thromboelastography testing. Methods: Using freshly collected whole blood from volunteers and stored red blood cells (RBC) and plasma, the whole blood was manipulated to achieve different Hct values and PLT concentrations. Each reconstituted whole blood sample was tested in triplicate on the ROTEM Delta device and the ExTEM results were recorded. Results: Many of the ExTEM results varied according to the Hct and PLT concentration. In particular, the ExTEM clot formation time (CFT) was abnormally long when the Hct was 45% and the PLT concentration was ≤75 × 109/L, normalizing only when the PLT count was ≥100 × 109/L. CFT samples with Hct 25% and 35% were also abnormal with low PLT concentrations but normalized at lower PLT concentrations compared to the Hct 45% samples. The ExTEM angle also demonstrated abnormal results when the Hct was 45% and the PLT concentration was ≤50 × 109/L. The ExTEM A10 and maximum clot firmness (MCF) tests tended to also be abnormal when the Hct was between 25% and 45% and the platelet concentrations were below 75 × 109/L. Conclusion: While thromboelastogram testing is gaining popularity for managing bleeding patients, clinicians should be aware of these confounding factors when making transfusion decisions based on their results. [ABSTRACT FROM AUTHOR]