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Mycobacterial diseases impact millions in the human and veterinary fields each year. Their diagnosis is long and laborious, often only sensitive in the late stages of disease. This has created an unmet need for new diagnostics that are effective in the earlier stages of infection and are quick and easy to perform. This study details the optimization of LAMP assays for the detection of M. tuberculosis, M. bovis and M. avium subsp. paratuberculosis combined with phage-mediated lysis to meet the needs of a novel diagnostic—termed phage-LAMP. The optimized phage-LAMP assay had a limit of detection of less than 10 mycobacteria per ml and no cross-reaction was seen between assays. The phage-LAMP method was then tested on a small number of clinical blood samples from suspected TB patients and herds suspected of Johne's disease. The phage-LAMP assay could detect viable Mycobacterium tuberculosis and M. avium subsp. paratuberculosis in these samples. [ABSTRACT FROM AUTHOR]

This case report highlights the rare association among a dental procedure, infective endocarditis, and an acute ischemic stroke. A 54-year-old woman who experienced an acute ischemic stroke 5 weeks after a tooth extraction is described. The initial symptoms of this patient included mild to moderate word-finding difficulty and right facial droop. Computed tomographic angiography revealed a left M1 segment middle cerebral artery occlusion (thrombolysis in cerebral infarction scale, 0) with reconstitution of the distal middle cerebral branches through arterial collaterals. After initial administration of tissue plasminogen activator, endovascular thrombectomy was successfully performed with thrombolysis in cerebral infarction scale 3 (complete) recanalization. After the procedure, the patient showed improvement in language and neurologic deficits. Imaging showed multifocal, bilateral, cortical, and deep brain hemorrhages. Blood cultures grew Streptococcus mitis , ultimately leading to the diagnosis of endocarditis. Echocardiographic imaging revealed moderate to severe aortic insufficiency, a mitral valve vegetation, and mild mitral valve regurgitation. After evaluation by the cardiothoracic surgery team, the patient was discharged with intravenous antibiotics and short-term outpatient follow-up with the cardiothoracic surgery team. Dental procedures, although generally safe, can introduce oral bacteria into the bloodstream, leading to bacterial seeding of cardiac valves and subsequent infective endocarditis. Recognizing infective endocarditis subsequent to a dental procedure, including a tooth extraction, as a potential cause of an acute ischemic stroke is vital so that prompt treatment can be initiated. [ABSTRACT FROM AUTHOR]

Eastern collared lizards (Crotaphytus collaris) are growing in popularity as exotic pets in the United States and worldwide. However, clinical biochemistry reference data to support the interpretation of health and disease for this species are lacking. This study evaluated 87 apparently healthy eastern collared lizards (C. collaris). Blood samples were collected from the ventral coccygeal vein and assayed via an Abaxis VetScan VS2 analyzer and avian/reptile profile plus rotor. Although lizard weight and snout–vent length (SVL) were normally distributed, most biochemical analytes, except albumin and total protein, were not. Many analytes were affected, albeit slightly, by lizard age, SVL, body condition score, gravidity and/or recent oviposition, sex, health status, and color and locality. However, except for calcium, phosphorous, and albumin for gravid or immediately postoviposition females, biochemical values remained within the generated reference interval. Limitations of this study included that the VetScan VS2 avian/reptile profile plus rotor was unable to successfully provide values for bile acids for most of these apparently healthy lizards. When compared to biochemistry analyte values of lizards from the suborder Iguania from the western hemisphere, eastern collared lizard biochemistries were similar for some analytes, but a relatively increased plasma glucose and uric acid occurs in this species, which could affect the diagnosis of clinical disease or other health abnormalities. [ABSTRACT FROM AUTHOR]

Background Nearly half of all pediatric musculoskeletal infections (MSKIs) are culture negative. Plasma microbial cell-free DNA (mcfDNA) sequencing is noninvasive and not prone to the barriers of culture. We evaluated the performance of plasma mcfDNA sequencing in identifying a pathogen, and examined the duration of pathogen detection in children with MSKIs. Methods We conducted a prospective study of children, aged 6 months to 18 years, hospitalized from July 2019 to May 2022 with MSKIs, in whom we obtained serial plasma mcfDNA sequencing samples and compared the results with cultures. Results A pathogen was recovered by culture in 23 of 34 (68%) participants, and by initial mcfDNA sequencing in 25 of 31 (81%) participants. Multiple pathogens were detected in the majority (56%) of positive initial samples. Complete concordance with culture (all organisms accounted for by both methods) was 32%, partial concordance (at least one of the same organism(s) identified by both methods) was 36%, and discordance was 32%. mcfDNA sequencing was more likely to show concordance (complete or partial) if obtained prior to a surgical procedure (82%), compared with after (20%), (RR 4.12 [95% CI 1.25, 22.93], p = .02). There was no difference in concordance based on timing of antibiotics (presample antibiotics 60% vs no antibiotics 75%, RR 0.8 [95% CI 0.40, 1.46], p = .65]). mcfDNA sequencing was positive in 67% of culture-negative infections and detected a pathogen for a longer interval than blood culture (median 2 days [IQR 1, 6 days] vs 1 day [1, 1 day], p < .01). Conclusions Plasma mcfDNA sequencing may be useful in culture-negative pediatric MSKIs if the sample is obtained prior to surgery. However, results must be interpreted in the appropriate clinical context as multiple pathogens are frequently detected supporting the need for diagnostic stewardship. [ABSTRACT FROM AUTHOR]

The presence of mycotoxins and their masked forms in chicken feed poses a significant threat to both productivity and health. This review examines the multifaceted impacts of mycotoxins on various aspects of chicken well-being, encompassing feed efficiency, growth, immunity, antioxidants, blood biochemistry, and internal organs. Mycotoxins, toxic substances produced by fungi, can exert detrimental effects even at low levels of contamination. The hidden or masked forms of mycotoxins further complicate the situation, as they are not easily detected by conventional methods but can be converted into their toxic forms during digestion. Consequently, chickens are exposed to mycotoxin-related risks despite apparently low mycotoxin levels. The consequences of mycotoxin exposure in chickens include reduced feed efficiency, compromised growth rates, impaired immune function, altered antioxidant levels, disturbances in blood biochemical parameters, and adverse effects on internal organs. To mitigate these impacts, effective management strategies are essential, such as routine monitoring of feed ingredients and finished feeds, adherence to proper storage practices, and the implementation of feed detoxification methods and mycotoxin binders. Raising awareness of these hidden hazards is crucial for safeguarding chicken productivity and health. [ABSTRACT FROM AUTHOR]

Granzyme B, mostly expressed by cytotoxic T lymphocytes in the fight against cancer and infection, is known to induce cell death based on its active enzymatic activity as a serine protease. Recent studies showed cytotoxicity of a non-enzymatic granzyme B-like peptide (also referred to as granzyme B-associated peptide or GP1 in this report) in tumor cells and presence of binding targets for GP1R (i.e., GP1 conjugated with rhodamine fluorochrome) in tumor cells, bacteria, and circulating platelets/neutrophils of healthy hosts. But there were no data on "sick" hosts to help substantiate any potential GP1 based medical applications. Thus, we adopted similar GP1R binding protocols to further study binding of GP1 in different biological samples (including different blood samples of hosts in sickness and in health, cancer cell lines, and trigeminal ganglia culture of infected hosts treated with and without GP1) and determine if any binding patterns might have any associations with different health conditions. The overall preliminary results appear to show certain GP1R + binding patterns in certain blood components (especially neutrophils) have potential correlations with certain health conditions of hosts at sampling times, indicating potential GP1R applications for diagnostic purposes. Findings of different GP1R binding patterns in different cancer cell lines, whole blood samples and trigeminal ganglia culture of experimental mice infected with HSV-1 virus (might cause neuropathy) within a week post-infection, and blood samples of GP1-treated mouse survivors on day 21 post-infection provided preliminary evidence of potential GP1-led tumor cell-specific cell death and treatment efficacy for greater survival. [ABSTRACT FROM AUTHOR]

Objective There are well-described impacts of biological rhythms on human physiology. With the increasing push for routine blood tests for preventative medical care and clinical and physiological research, optimizing effectiveness is paramount. This study aimed to determine whether it is feasible to assess diurnal variations of peripheral lymphocyte prevalence using finger prick blood in a small sample size. Methods Using polychromatic flow cytometry, the prevalence of lymphocytes was assessed using 25 µL fingertip blood samples at 8 AM and 5 PM from 8 participants. Results TH cells and B cells showed significantly higher percentages in the 5 PM samples, whereas NK cells demonstrated a significantly higher morning percentage. T cells, leukocytes, and cytotoxic T cells showed no significant changes. Conclusion The detection of diurnal variations demonstrates that small blood volumes can be used to detect lymphocyte variations. The lower blood volume required provides a new testing method for clinical and research settings. [ABSTRACT FROM AUTHOR]

Objective This study aimed to evaluate the impact of short-term incubation (STI) protocol on clinical outcomes of bloodstream infection (BSI) patients. Methods A total of 1363 positive blood culture records from January 2019 to December 2021 were included. The main clinical outcomes included pathogen identification turnaround time (TAT), antimicrobial susceptibility testing (AST) TAT, and length of total hospital stay. Results The TAT of pathogen identification and AST significantly decreased after implementing the STI protocol (2.2 vs 1.4 days and 3.4 vs 2.5 days, respectively, with P <.001 for both). Moreover, for patients with Gram-negative bacteria (GNB)–infected BSIs, the length of total hospital stay decreased from 31.9 days to 27.1 days, indicating that these patients could be discharged 5 days earlier after implementing the STI protocol (P <.01). Conclusion The protocol led to a significant reduction in TAT and improved clinical outcomes, particularly for GNB organisms. The findings suggest that the STI protocol can improve patient outcomes and hospital resource utilization in the management of BSIs. [ABSTRACT FROM AUTHOR]

Background: In Australia, a man cannot donate blood if he has had sex with another man within the past 3 months. However, this policy has been criticized as being discriminatory as it does not consider lower risk subgroups, and led to calls for modifications to the policy that more accurately distinguish risk among gay, bisexual, and other men who have sex with men (GBM). Study Design and Methods: We used data from a nationally representative survey to estimate the proportion of GBM aged 18–74 years old who would be eligible to donate under current criteria and other scenarios. Results: Among the 5178 survey participants, 155 (3.0%) were classified as GBM based on survey responses, Among the GBM, 40.2% (95% CI 28.0%–53.7%) were eligible to donate based on current criteria, and 21.0% (95% CI 14.5%–29.5%) were ineligible due to the 3 months deferral alone. Eligibility among GBM, all men, and the population increased as criteria were removed. Under the new Australian plasma donation criteria, 73.6% (95% CI 64.4%–81.1%) of GBM, 68.4% (95% CI 65.5%–71.2%) of all men, and 60.8% (95% CI 58.8%–62.8%) of the full population were estimated to be eligible. Only 16.1% (95% CI 8.6%–28.1%) of GBM knew that the male‐to‐male sex deferral period is 3 months. Discussion: Changing the deferral criteria and sexual risk evaluation would lead to a higher proportion of GBM being eligible to donate blood. Knowledge of the current GBM deferral period is very low. Improved education about the current criteria and any future changes are required to improve blood donation rates. [ABSTRACT FROM AUTHOR]

Background/Aims: The physiological phenotype of individuals can influence and shape reallife phenomena in that it can contribute to the development of specific characteristics that can affect the immune response to specific stimuli. In this study we aimed to understand whether the sphingosine/sphingosine-1-phoshate (S1P) axis can modulate the immunotype of circulating cells. Methods: To pursue this goal, we performed bioinformatic analyses of public datasets. Results: The transcriptomic profile of healthy subjects of GSE192829 dataset identified two clusters with different transcriptional repertoire. Cluster 1 expressed higher levels of enzymes for S1P formation than cluster 0 which was characterized by enzymes that lead to ceramide formation, which represent the opposite metabolic direction. Inference analysis showed that cluster 1 was higher populated by monocytes, CD4+ T and B cells than cluster 0. Of particular interest was the phenotype of the monocytes in cluster 1 which showed an immunosuppressive nature compared to those in cluster 0. The role of S1P signature in healthy PBMCs was confirmed with other dataset analyses, supporting that circulating monocytes positive to the ceramidase, unlike the negative ones, had an immunosuppressive phenotype characterized by hub immunosuppressive markers (i.e. TYROBP, FCER1G, SYK, SIRPA, CSF1R, AIF1, FCGR2A, CLEC7A, LYN, PLCG2, LILRs, HCK, GAB2). This hub genes well discriminated the immunotype of healthy subjects. Conclusion: In conclusion this study highlights that S1P-associated hub markers can be useful to discriminate subjects with pronounced immunosuppression. [ABSTRACT FROM AUTHOR]

Background: Intensive care units have become hotspots for antimicrobial resistance, particularly concerning colistin resistance, posing a threat of untreatable infections. Aim: This study aims to analyze the epidemiological and clinical aspects of patients carrying colistin-resistant organisms. It focuses on identifying risk factors, the microbiological profile, susceptibility patterns, and treatment outcomes. Materials and methods: Isolates with colistin MIC >2 µg/mL, identified via BD PHOENIX, were subjected to colistin broth disc elution testing (as per CLSI guidelines) in our Microbiology Department between January and December 2022. Results: Among the 30 patients, colistin-resistant gram-negative isolates were found predominantly in blood cultures (50%), followed by ET/ TT cultures (23.3%), urine cultures (10%), and other sites (16.7%). Klebsiella pneumoniae was the most common organism (80%), showing the highest sensitivity to Ceftazidime-avibactam + Aztreonam (CAZ-AVI + ATM) (76.7%). Of these patients, 66.7% recovered and were discharged, while 33.3% succumbed during hospitalization despite treatment. Conclusion: The study underscores a notable presence of colistin-resistant gram-negative isolates, predominantly in blood cultures, with K. pneumoniae being predominant. The combination of CAZ-AVI + ATM exhibited the highest sensitivity. However, the mortality rate of 33.3% despite sensitive antibiotic treatment highlights the urgency for ongoing vigilance and research to combat colistin-resistant infections and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Synthetic meat made from animal cells will transform how we eat. It will reduce suffering by eliminating the need to raise and slaughter animals. But it will also have big public health benefits if it becomes widely consumed. In this paper, we discuss how "clean meat" can reduce the risks associated with intensive animal farming, including antibiotic resistance, environmental pollution, and zoonotic viral diseases like influenza and coronavirus. Since the most common objection to clean meat is that some people find it "disgusting" or "unnatural," we explore the psychology of disgust to find possible counter-measures. We argue that the public health benefits of clean meat give us strong moral reasons to promote its development and consumption in a way that the public is likely to support. We end by depicting the change from farmed animals to clean meat as a collective action problem and suggest that social norms rather than coercive laws should be employed to solve the problem. [ABSTRACT FROM AUTHOR]

Impaired angiogenesis is associated with cognitive decline in older adults. While exercise has been broadly associated with increased angiogenesis, the relevant mechanisms in older adults are not clear. Here, we present a systematic review and meta-analysis on the relationship between exercise and specific blood angiogenesis markers in older adults to better understand the relevant mechanisms. MEDLINE, Embase, and Cochrane CENTRAL were searched for original reports of angiogenesis markers' concentrations in blood before and after exercise in older adults (≥50 years). Heterogeneity was investigated using sub-group analyses and meta-regressions. Of the 44 articles included in the review, 38 were included in the meta‐analyses for five markers: vascular endothelial growth factor (VEGF), e-selectin (CD62E), endostatin, fibroblast growth factor 2, and matrix metallopeptidase-9. VEGF levels were higher (SMD[95%CI]= 0.18[0.03, 0.34], and CD62E levels were lower (SMD[95%CI]= −0.72[−1.42, −0.03], p = 0.04) after exercise. No other markers were altered. Although more studies are needed, changes in angiogenesis markers may help explain the beneficial effects of exercise on angiogenesis in older adults. • Meta-analysis on exercise and angiogenesis blood markers in older adults. • Only some angiogenesis markers showed changes with exercise. • Vascular endothelial growth factor (VEGF) levels were higher after aerobic exercise. • E-selectin (CD62E) levels were lower after exercise. [ABSTRACT FROM AUTHOR]

Simple Summary: The growing female calves are the future of the dairy farms and their balanced growth yields benefits in their adult lives. Natural herbal products and their extracts are considered as digestive stimulants, immune enhancers and anti-oxidants. The additions of these phytogenic extracts have proven to be beneficial in animals. This study involved the addition of myrtus leaves and root extract in the milk of the suckling calves and observed its benefits on their health, performance and immune status in the following days. It is concluded that the addition of the myrtus extract results in the improvement in the overall performance, reproduction and health status of the animals. This research aimed to understand the effects of adding myrtle plant extract obtained from its leaves (MPEL) and roots (MPER) to the milk fed to suckling female Holstein calves, focusing on performance, reproduction, selected blood parameters and immune response. The 50 Holstein female calves, one week of age, were divided into five groups: one group received no plant extract (Control), while the others were supplemented with myrtle plant extracts at doses of 25 mL/day leaf extract (MPEL-25), 25 mL/day root extract (MPER-25), 50 mL/day leaf extract (MPEL-50) and 50 mL/day root extract (MPER-50) for each calf in each treatment group. The extracts were given along with the milk to the experimental groups for 60 days, and for an additional 12 days post-weaning. The results reveal that the feed consumption and live weights increased significantly. Significantly higher leukocyte counts were observed in the 50 mL/head × day myrtle groups, and a higher IgG concentration was also noted in the MPER-50 group compared to the other groups. The serum non-esterified fatty acid (NEFA) concentration significantly decreased in the MPEL-50 and MPER-50 groups, whereas the betahyrdoxy butyric acid (BHBA) concentration increased and the serum glucose concentration significantly decreased with myrtle supplementation. In conclusion, it was determined that the performance, immune system and negative energy balance compensation of female Holstein calves were positively affected by administering extracts obtained from the leaves and roots of the Myrtus communis L. plant at dose levels of 25 and 50 mL/head × day for 72 days, without causing any side effects. [ABSTRACT FROM AUTHOR]

Body fluid identification is fundamental in forensic science as it links a specific biological source to a genetic profile, thus providing critical clues for crime scene reconstruction. Blood is one of the most common body fluids found on the crime scene, and several strategies have been developed for its identification in recent decades. Usually, after a preliminary (or presumptive) test to determine the presence of blood (both human and non-human), a confirmatory test is needed to prove that the sample is human blood. Out of the confirmatory tests, immunochromatographic (IC) assays are the most commonly and widely used. This work gives a review of the use of commercial kits specifically developed to detect human hemoglobin or glycophorin A (a surface protein of human red cells) in forensics. Claimed sensitivity varies broadly (ranging from 0.06 to 75 nanoliters of fresh blood), but different values (as low as 0.002 nL) were found during validation procedures. Specificities are high, and the possibility of cross-reaction (with the risk of false-positive results) is so low that it can be considered negligible. False-negative results, however, can be found due to the so-called "hook effect" as well as to the target degradation/modification, which interferes with the Ag-Ab binding. In addition, the chemical compositions of the presumptive test, detergents, and washing can also promote false negative outcomes in peculiar situations. Although IC assays are rapid, inexpensive, specific, and easy to use even on the crime scene, their major limitation is represented by the destructive approach required by this kind of confirmatory test. Since the final goal of the forensic investigation is the genetic typing of a bloodstain, we will describe the strategies developed for IC assays of faint stains as well as the strategies adopted to ensure that exactly the same sample undergoes human blood identification and DNA typing. [ABSTRACT FROM AUTHOR]

Background: Accidental dural puncture (ADP) is the most frequent major complication when performing an epidural procedure in obstetrics. Consequently, loss of pressure in the cerebrospinal fluid (CSF) leads to the development of post‐dural puncture headache (PDPH), which occurs in 16%–86% of cases. To date, the efficacy of epidural fibrin patches (EFP) has not been evaluated in a controlled clinical trial, nor in comparative studies with epidural blood patches (EBP). Methods: The objective of the present study was to compare the efficacy of EFP with respect to EBP for the treatment of refractory accidental PDPH. This prospective, randomized, open‐label, parallel, comparative study included 70 puerperal women who received an EBP or EFP (35 in each group) after failure of the conventional analgesic treatment for accidental PDPH in a hospital. Results: A higher percentage of women with EFP than EBP achieved complete PDPH relief after 2 (97.1% vs. 54.3%) and 12 h (100.0% vs. 65.7%) of the patch injection. The percentage of patients who needed rescue analgesia was significantly lower with EFP after 2 (2.9% vs. 48.6%) and 12 h (0.0% vs. 37.1%). After 24 h, PDPH was resolved in all women who received EFP. The recurrence of PDPH was reported in one woman from the EBP group (2.9%), who subsequently required a second patch. The mean length of hospital stay was significantly lower with EFP (3.9 days) than EBP (5.9 days). Regarding satisfaction, the mean value (Likert scale) was significantly higher with EFP (4.7 vs. 3.0). Conclusions: EFP provided better outcomes than EBP for the treatment of obstetric PDPH in terms of efficacy, safety, and patient satisfaction. [ABSTRACT FROM AUTHOR]

Despite current advances in body fluid identification, there are few studies evaluating the effect of environmental conditions. The present work assessed the detection of body fluids, blood, semen, and saliva, through lateral flow immunochromatographic (LFI) tests, exposed to tropical weather conditions over time, also evaluating the possibility of obtaining STR (short tandem repeat) profiles and identifying mitochondrial DNA (mtDNA) polymorphisms. Blood, semen, saliva samples, and mixtures of these fluids were deposited on polyester clothes and exposed to open‐air tropical weather conditions for 1 month. The test versions from LFI (SERATEC®, Germany) Lab and crime scene (CS) used for the detection – one per each body fluid type – demonstrated that it is possible to identify body fluids and their mixtures up to 14 days after deposition. At 30 days, blood and semen were detected but not saliva. Full STR profiles were obtained from 14‐day‐old blood samples, and partial profiles were obtained from the remaining samples. It was possible to sequence mtDNA in the samples previously analyzed for STR profiling, and haplogroups could be assigned. In conclusion, this study demonstrated for the first time the possibility of body fluid identification and DNA profiling after exposure to tropical weather conditions for 1 month and also demonstrated the value of mtDNA analysis for compromised biological evidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer patients with a specific gene mutation often undergo tissue biopsies to guide treatment. But what if a simple blood test could do the same? This review explores "liquid biopsies", which detect circulating tumor DNA (ctDNA) in the blood, offering several advantages. For early-stage disease, it could help decide on treatment after surgery. In advanced stages, it can identify genetic changes in the tumor that might affect treatment response. Additionally, tracking ctDNA levels can monitor treatment progress and detect resistance early. While tissue biopsies remain standard, liquid biopsies are becoming a recommended alternative. Ongoing research aims to improve test sensitivity for early detection, refine treatment approaches based on ctDNA results, and explore other bodily fluids for even better detection. Making liquid biopsies more accessible and integrated into routine care could significantly improve lung cancer management. Circulating tumor DNA (ctDNA) offers a new paradigm in optimizing treatment strategies for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Its potential spans early-stage disease, influencing adjuvant therapy, to advanced disease, where it aids in identifying genomic markers and resistance mechanisms. This review explores the evolving landscape of utilizing liquid biopsies, specifically circulating tumor DNA (ctDNA), in the management of NSCLC with EGFR mutations. While tissue-based genomic testing remains the cornerstone for clinical decision-making, liquid biopsies offer a well-validated, guideline-recommended alternative approach. Ongoing trials integrating ctDNA for EGFR-mutant NSCLC management are also discussed, shedding light on the potential of ctDNA in early-stage disease, including its applications in prognostication, risk stratification, and minimal residual disease detection post-curative intent treatment. For advanced disease, the role of ctDNA in identifying resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs) is explored, providing insights into disease progression and guiding treatment decisions. This review also addresses the challenges, including the limitations in sensitivity of current assays for disease recurrence detection, and calls for future studies to refine treatment approaches, standardize reporting, and explore alternative biofluids for enhanced sensitivity. A systematic approach is crucial to address barriers to ctDNA deployment, ensuring equitable access, and facilitating its integration into routine clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Blood clots are formed when blood vessels are injured. They help stop bleeding and heal wounds, but can also cause serious problems if they block blood flow or break off and travel to other organs. This study investigates how blood clots differ in people with cancer compared to healthy or non-cancerous individuals. This study found that cancer patients have higher levels of histones in their blood, which make their clots stiffer and resistant to lysis. Further, clots formed in cancer patients have higher viscoelastic properties, and hence are harder to break down. These findings suggest that cancer patients have abnormal clotting properties that may increase their risk of developing thrombosis, and evaluating these properties can be helpful in detecting cancer. Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots' permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Circulating tumor DNA (ctDNA) is emerging as a diagnostic and surveillance tool in cancer and recurrence. The recurrence rates after liver transplant for cancer are significant, highlighting the need for early detection and treatment. We report a cohort of patients who underwent liver transplant for hepatocellular carcinoma, cholangiocarcinoma, or colorectal cancer liver metastasis and received ctDNA testing pre- and/or post-transplant. We aim to show how ctDNA testing can be incorporated into pre-transplant work-up and post-transplant surveillance and discuss the benefits of this testing modality in the identification of genetic targets and surveillance of recurrence. Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. Results: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1–124). The median time from pre-operative testing to surgery was 3 months (IQR: 1–4; range: 0–5), and from surgery to post-operative testing, it was 9 months (IQR: 2–22; range: 0.4–112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6–40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/−). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA−/− (n = 1, 10%), and ctDNA−/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. Conclusions: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns. [ABSTRACT FROM AUTHOR]

Simple Summary: As a tumor grows, DNA fragments from cancer cells shed into the bloodstream. Known as circulating tumor DNA (ctDNA), these fragments can be used to inform on cancer diagnosis, treatment, and prognosis. However, despite the potential for these uninavasive liquid biopsies to revolutionize cancer monitoring and treatment, ctDNA can show poor genetic concordance between blood and the main tumor tissue, hampering its general clinical utility. For liquid biopsy technologies and ctDNA analyses to transform cancer care, from early screening and diagnosis through treatment and long-term follow-up, we need to better understand how to interpret the genetic diversity measured in the blood and how it can be used to describe the true composition of the tumor tissue. In this work we study the evolutionary processes that can lead to genetic discordance between a blood sample and the main tumor tissue and specifically, how tumor spatial heterogeneity shapes these genetic differences. We find that spatial heterogeneity in apoptosis and cellular shedding across different regions of a tumor can significantly bias the mutational composition of ctDNA and emphasize important directions for further theoretical and clinical investigation into the effect of the microenvironment on ctDNA origin and quantification. Circulating tumor DNA (ctDNA) monitoring, while sufficiently advanced to reflect tumor evolution in real time and inform cancer diagnosis, treatment, and prognosis, mainly relies on DNA that originates from cell death via apoptosis or necrosis. In solid tumors, chemotherapy and immune infiltration can induce spatially variable rates of cell death, with the potential to bias and distort the clonal composition of ctDNA. Using a stochastic evolutionary model of boundary-driven growth, we study how elevated cell death on the edge of a tumor can simultaneously impact driver mutation accumulation and the representation of tumor clones and mutation detectability in ctDNA. We describe conditions in which invasive clones are over-represented in ctDNA, clonal diversity can appear elevated in the blood, and spatial bias in shedding can inflate subclonal variant allele frequencies (VAFs). Additionally, we find that tumors that are mostly quiescent can display similar biases but are far less detectable, and the extent of perceptible spatial bias strongly depends on sequence detection limits. Overall, we show that spatially structured shedding might cause liquid biopsies to provide highly biased profiles of tumor state. While this may enable more sensitive detection of expanding clones, it could also increase the risk of targeting a subclonal variant for treatment. Our results indicate that the effects and clinical consequences of spatially variable cell death on ctDNA composition present an important area for future work. [ABSTRACT FROM AUTHOR]

Background: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis. Hypothesis: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers. Animals: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17). Methods: A retrospective case‐control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, mouse, and human genomes. Differentially expressed microRNAs were identified and the potential mechanistic relevance explored using Qiagen Ingenuity Pathway Analysis (IPA). Results: Reads mapping to 196 mature microRNA sequences were detected. Eight circulating microRNAs were significantly differentially expressed in dogs with pancreatitis (≥2‐fold change and false discovery rate <0.05). Four of these mapped to the canine genome (cfa‐miR‐221, cfa‐miR‐222, cfa‐miR‐23a, and cfa‐miR‐205). Three mapped to the murine genome (mmu‐miR‐484, mmu‐miR‐6240, mmu‐miR‐101a‐3p) and 1 to the human genome (hsa‐miR‐1290). Expression in dogs with pancreatitis was higher for 7 microRNAs and lower for mmu‐miR‐101a‐3p. Qiagen IPA demonstrated a number of the differently expressed microRNAs are involved in a common pancreatic inflammatory pathway. Conclusions: The significantly differentially expressed microRNAs represent promising candidates for further validation as diagnostic biomarkers for canine pancreatitis. [ABSTRACT FROM AUTHOR]

The genus Sarcocystis is an abundant group of Apicomplexa parasites found in mammals, birds, and reptiles. These parasites are characterised by the formation of sarcocysts in the muscles of intermediate hosts and the development of sporocysts in the intestines of definitive hosts. The identification of Sarcocystis spp. is usually carried out in carcasses of animals, while there is a lack of studies on the detection of Sarcocystis species in blood samples. In the current study, blood samples of 214 yellow-necked mice (Apodemus flavicollis) and 143 bank voles (Clethrionomys glareolus) from Lithuania were examined for Sarcocystis. The molecular identification of Sarcocystis was carried out using nested PCR of cox1 and 28S rRNA and subsequent sequencing. Sarcocystis spp. were statistically (p < 0.01) more frequently detected in the bank vole (6.3%) than in yellow-necked mice (0.9%). The analysed parasites were observed in four different habitats, such as mature deciduous forest, bog, natural meadow, and arable land. Three species, Sarcocystis funereus, Sarcocystis myodes, and Sarcocystis cf. glareoli were confirmed in the bank vole, whereas only Sarcocystis myodes were found in yellow-necked mice. The obtained results are important in the development of molecular identification of Sarcocystis parasites in live animals. [ABSTRACT FROM AUTHOR]

Adenosine is a multifunctional nucleoside with several roles across various levels in organisms. Beyond its intracellular involvement in cellular metabolism, extracellular adenosine potently influences both physiological and pathological processes. In relation to its blood level, adenosine impacts the cardiovascular system, such as heart beat rate and vasodilation. To exploit the adenosine levels in the blood, we employed the liquid chromatography method coupled with mass spectrometry (LC–MS). Immediately after collection, a blood sample mixed with acetonitrile solution that is either enriched with 13C-labeled adenosine or a newly generated mixture is transferred into the tubes containing the defined amount of 13C-labeled adenosine. The 13C-enriched isotopic adenosine is used as an internal standard, allowing for more accurate quantification of adenosine. This novel protocol for LC–MS-based estimation of adenosine delivers a rapid, highly sensitive, and reproducible means for quantitative estimation of total adenosine in blood. The method also allows for quantification of a few catabolites of adenosine, i.e., inosine, hypoxanthine, and xanthine. Our current setup did not allow for the detection or quantifying of uric acid, which is the final product of adenosine catabolism. This advancement provides an analytical tool that has the potential to enhance our understanding of adenosine's systemic impact and pave the way for further investigations into its intricate regulatory mechanisms. [ABSTRACT FROM AUTHOR]

Background and Objectives: Although screening of donated blood for syphilis is almost universally applied, its cost‐effectiveness is questioned because of the low prevalence of transfusion‐transmitted syphilis and a widespread belief that the syphilis‐causing bacterium Treponema pallidum is very vulnerable to cold storage. Since the latter claim is not yet supported by a systematic review, we investigated whether syphilis can be transmitted via transfusion following prolonged (cold or room temperature) storage of blood products. Materials and Methods: MEDLINE, PMC and NCBI bookshelf (PubMed interface), Cochrane Library, Embase, Web of Science and CINAHL were searched up to 17 January 2023. Results: Nine experimental animal studies and one observational human study were included. Meta‐analysis showed that storing artificially infected human (six studies; risk ratio [RR] = 0.37, 95% confidence interval [CI]: 0.22–0.64, p = 0.0003) or rabbit (two studies; RR = 0.08, 95% CI: 0.01 to 0.55, p = 0.01) blood for more than 72 h before intratesticular injection significantly decreased the number of recipient animals that develop syphilis. Nonetheless, the possibility of syphilis transmission remained for up to 7 days. Differences could not be found for rabbit plasma (p = 0.60) or naturally infected rabbit blood (p = 0.28). There was limited evidence from one study in favour of the storage of artificially infected human platelets for over 72 h at cold temperatures (RR = 0.13, 95% CI: 0.03–0.52, p = 0.004) but not at room temperature (p = 0.12). Conclusion: Even though the infectivity of T. pallidum‐spiked blood may decrease after 72 h of cold storage, the possibility for transfusion‐transmitted syphilis may remain for several days after. The evidence is very uncertain, and conclusions are hindered by a lack of sufficiently powered studies and studies in humans. In addition, T. pallidum concentrations used in animal studies may be unrealistically high. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs have been shown to be involved in a myriad of physiological and pathological pathways. To date, malignant pleural mesothelioma (MPM) is considered an extremely aggressive cancer. One reason for this is the late diagnosis of the disease, which can occur within 30–40 years of asbestos exposure. There is an immense need for the development of new, sensitive, inexpensive and easy methods for the early detection of this disease other than invasive methods such as biopsy. The aim of this study was to determine the expression of circulating lncRNAs in mesothelioma patient plasma to identify potential biomarkers. Ten previously identified lncRNAs that were shown to be aberrantly expressed in mesothelioma tissues were selected as candidates for subsequent validation. The expression of the ten selected candidate lncRNAs was verified via quantitative PCR (qPCR) in human plasma samples from mesothelioma patients versus healthy controls. The expression levels of circulating GAS5, SNHG8 and MALAT1 were significantly greater in plasma samples from patients than in those from controls. The ROC analysis of both MALAT1 and SNHG8 revealed 88.89% sensitivity and 66.67% specificity. The sensitivity of these markers was greater than that of GAS5 (sensitivity 72.22% and specificity 66.67%). The regression model for GAS5 was statistically significant, while that for SNHG8 and MALAT1 was not significant due to the small sample size. The area under the curve (AUC) of the three ROC curves was acceptable and significant: 0.7519 for GAS5, 0.7352 for SNHG8 and 0.7185 for MALAT1. This finding confirmed their ability to be used as markers. The three lncRNAs were not affected by age, sex or smoking status. The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5. [ABSTRACT FROM AUTHOR]

Background: Wistar rats are extensively used as the model for assessing toxicity and efficacy in preclinical research. Hematological and biochemical laboratory data are essential for evaluating specific variations in the physiological and functional profile of a laboratory animal. Establishing hematological and biochemical reference values for Wistar (han) rats at various age intervals was the goal of this work. Male and female Wistar rats (n = 660) of ages 6–8 weeks, 10–14 weeks and > 6 months were used in the experiment. Blood and serum were collected from these rats under fasting conditions. Results: We observed that the majority of hematological and biochemical parameters were significantly influenced by sex and age. Hematological changes were significantly correlated to aging were increased red blood cells, hemoglobin, hematocrit, neutrophils, monocytes and eosinophils in both sexes, as well as decreased platelet, mean corpuscular volume, mean corpuscular hemoglobin and lymphocytes in both sexes. White blood cells of male rats were considerably higher than those of female rats in all age ranges. For biochemistry, increase in glucose, total protein and creatinine were seen in both sexes, along with increases in urea in females and alanine aminotransferase in males. Age was significantly associated with decreased alkaline phosphatase in both sexes. Conclusions: When using Wistar rats as a model, these reference values may be useful in evaluating the results. [ABSTRACT FROM AUTHOR]

BackgroundObjectivesMethodsResultsConclusionClinical Trials RegistrationPatients with fibromyalgia experience chronic, widespread pain. It remains a misunderstood disorder with multimodal treatments providing mixed results.To examine the effects of radial shockwave therapy (RSWT) compared to placebo on pain, pain catastrophizing, psychological indices, blood markers, and neuroimaging. Study-related experiences were also explored qualitatively.Quantitative sensory testing (QST), Visual Analog Scale (VAS), Beighton Scoring Screen (BSS), Pain Catastrophizing Scale (PCS), blood biomarker (Interleukin (IL)-6 and IL-10), and brain fMRI were measured pre- and post-treatment along with a post-treatment survey. The RSWT group received five treatments (one week apart over five-week period) to the three most painful areas (500 shocks at 1.5 bar and 15 Hz, then 1000 shocks at 2 bar and 8 Hz, and finally 500 shocks at 1.5 bar and 15 Hz) versus sham treatment for the placebo group.There were no statistically significant differences in the BSS for hypermobility (p = .21; d = .74), PCS (p = .70; d = .22), VAS (p = .17–.61; d = .20–.83) scores, QST for skin temperature and stimuli (p = .14–.65; d = .25–.88), and for the pressure pain threshold (p = .71–.93; d = .05–.21). The VAS scores had clinically significant changes (MCID greater than 13.90) with improved pain scores in the RSWT group. Neuroimaging scans revealed no cortical thickness changes. Post-treatment surveys revealed pain and symptom improvements and offered hope to individuals.RSWT was implemented safely, without any negative treatment effects reported, and acted as a pain modulator to reduce sensitivity.ClinicalTrials.gov identification number NCT02760212 [ABSTRACT FROM AUTHOR]

Background: Commercial diets are frequently formulated to meet or exceed nutrient levels including those of limiting essential amino acids (AA) covering potential individual variations within the herd. However, the provision of dietary excess of AA, such as Lys, may lead to reduced appetite and growth in pigs. The mechanisms modulating these responses have not been extensively investigated. This study evaluated the effect of Lys dietary excesses on performance and satiety biomarkers in post weaning pigs. Methods: Twenty-four pigs aged 21 d and weighing 6.81 ± 0.12 kg (mean ± SEM) were individually housed and offered 1 of 4 dietary treatments for 3 weeks: a diet containing a standardized ileal digestible Lys reaching 100% (T0), 120% (T1), 150% (T2) or 200% (T3) of the NRC (2012) requirements. At the end of the experiment, blood samples from the cephalic vein of the T0 and T3 groups were obtained for AA analysis. In addition, primary intestinal cultures from T0 pigs were used, following their humane killing, to evaluate the effect of Lys on gut hormone secretion and AA sensors gene expression under ex vivo conditions. Results: Feed intake was linearly reduced (P < 0.001) and the weight gain to feed ratio reduced (P < 0.10) with increased dietary levels of Lys during the third- and first-week post weaning, respectively. Cholecystokinin concentration (P < 0.05) and the metabotropic glutamate receptor 1 and the solute carrier family 7 member 2 (P < 0.10) gene expression was enhanced in proximal jejunum tissues incubated with Lys at 20 mmol/L when compared to the control (Lys 0 mmol/L). Plasma Lys and Glu (P < 0.05) concentration increased in the T3 compared to T0 pigs. In contrast, plasma levels of His, Val, Thr, Leu (P < 0.05) and Gln (P < 0.10) were lower in T3 than T0 pigs. Conclusion: The present results confirm that excess dietary Lys inhibits hunger in pigs. Moreover, the results provide evidence of pre- and post-absorptive mechanisms modulating these responses. Lys dietary excesses should be narrowed, when possible, to avoid negative effects of the AA on appetite in pigs. [ABSTRACT FROM AUTHOR]

Objective. This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients with chronic kidney disease (CKD) stages 3–5. Methods. From December 2021 to January 2023, a total of 108 CKD patients in stages 3–5 were enrolled in this cross-sectional investigation. Demographic information and routine clinical biochemistry test results were gathered. Serum levels of IS and Klotho were quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed to evaluate vascular calcification. The association between serum IS or Klotho levels and abdominal aorta calcification was assessed using univariate analysis and logistic regression analyses. Results. With the progression of CKD stages, serum creatinine, phosphorus, intact parathyroid hormone (iPTH), serum IS, and abdominal aortic calcification exhibited incremental trends, while serum calcium and Klotho protein levels showed a diminishing trend, with statistically significant differences (P < 0. 05). Significant differences were observed in age, blood phosphorus, calcium, total parathyroid hormone, serum IS, and Klotho protein levels between patients with and without aortic calcification (P < 0. 05). Logistic regression analysis demonstrated that advanced age, high IS level, and low Klotho protein level were independent risk factors for abdominal aortic calcification in CKD patients (P < 0. 05). Conclusion. This study indicates elevated serum IS levels and decreased Klotho protein levels in CKD patients. High IS level and low Klotho level were independent risk factors for abdominal aortic calcification. [ABSTRACT FROM AUTHOR]

Cyclic tetrapyrrole derivatives such as porphyrins, chlorins, corrins (compounds with a corrin core), and phthalocyanines are a family of molecules containing four pyrrole rings usually coordinating a metal ion (Mg, Cu, Fe, Zn, etc.). Here, we report the characterization of some representative cyclic tetrapyrrole derivatives by MALDI-ToF/ToF MS analyses, including heme b and c, phthalocyanines, and protoporphyrins after proper matrix selection. Both neutral and acidic matrices were evaluated to assess potential demetallation, adduct formation, and fragmentation. While chlorophylls exhibited magnesium demetallation in acidic matrices, cyclic tetrapyrroles with Fe, Zn, Co, Cu, or Ni remained steadfast against demetallation across all conditions. Phthalocyanines and protoporphyrins were also detectable without a matrix using laser desorption ionization (LDI); however, the incorporation of matrices achieved the highest ionization yield, enhanced sensitivity, and negligible fragmentation. Three standard proteins, i.e., myoglobin, hemoglobin, and cytochrome c, were analyzed either intact or enzymatically digested, yielding heme b and heme c ions along with accompanying peptides. Furthermore, we successfully detected and characterized heme b in real samples, including blood, bovine and cod liver, and mussel. As a result, MALDI MS/MS emerged as a powerful tool for straightforward cyclic tetrapyrrole identification, even in highly complex samples. Our work paves the way for a more comprehensive understanding of cyclic tetrapyrroles in biological and industrial settings, including the geochemical field, as these compounds are a source of significant geological and geochemical information in sediments and crude oils. [ABSTRACT FROM AUTHOR]

Simple Summary: Welfare assessment of horses used in equine disciplines such as 3-barrels must incorporate both invasive and noninvasive methods. Ten Quarter Horses regularly participating in 3TB competitions were evaluated through infrared thermography and blood biomarkers to determine the effects of a short interval between races on their health and well-being. These animals performed two races of 3TB at 2 min intervals, and samples were obtained before and during the recovery period in four moments. The physiological responses observed in experimental horses indicated changes in some parameters within 1 h after races on surface temperatures but with no differences compared to pre-race records. Parameters usually used to assess well-being and health in athletic horses did not change. We conclude that well-conditioned 3TB horses are not harmed by running two races with short intervals between them. Equestrian sports require precise animal welfare and health evaluations. To test the hypothesis that horses maintain their welfare when subjected to two three-barrel (3TB) races with 2 min intervals, an experiment was designed to evaluate their surface temperature using infrared thermography (IRT) in regions of interest (barrel, flank, neck, jaw, corner of the mouth, and ocular caruncle) and also measure blood biomarkers (hemogram, total plasma protein, fibrinogen, urea, creatinine, GGT, CK, cortisol, IL-6, and IL-1β). Ten Quarter Horses were monitored through thermography (pre-race, +1, +4, and +24 h post-race) and blood sampling (pre-race, +1, +4, and +24 h post-race). ANOVA and Tukey test at 5% were used. IRT in six regions of interest (Left/Right—barrel, flank, neck muscles) increased at +, with no differences between values recorded at +1 and +4 when compared to those measured pre-race (p > 0.05). Plasma protein, RBC count, hemoglobin, hematocrit, WBC count, neutrophils, and lymphocytes (p < 0.05) increased immediately after the races, with recovery at +1 h. Other biomarkers did not change, including cortisol, IL-6, and IL-1β (p > 0.05). Results indicate that well-conditioned 3TB horses subjected to two races at short intervals do not show changes that could be related to impaired health or welfare. [ABSTRACT FROM AUTHOR]

Our study employs machine learning to predict serum valproic acid (VPA) concentrations, aiming to contribute to the development of non-invasive assays for therapeutic drug monitoring. Medical records from 2002 to 2019 were obtained from the Taiwan Chang Gung Research Database. Using various machine learning algorithms, we developed predictive models to classify serum VPA concentrations into two categories (1–50 μg/ml or 51–100 μg/ml) and predicted the exact concentration value. The models were trained on 5142 samples and tested on 644 independent samples. Accuracy was the main metric used to evaluate model performance, with a tolerance of 20 μg/ml for continuous variables. Furthermore, we identified important features and developed simplified models with fewer features. The models achieved an average accuracy of 0.80–0.86 for binary outcomes and 0.72–0.88 for continuous outcome. Ten top features associated with higher serum VPA levels included higher VPA last and daily doses, bipolar disorder or schizophrenia spectrum disorder diagnoses, elevated levels of serum albumin, calcium, and creatinine, low platelet count, low percentage of segmented white blood cells, and low red cell distribution width-coefficient of variation. The simplified models had an average accuracy of 0.82–0.86 for binary outcome and 0.70–0.86 for continuous outcome. The study's predictive model lacked external test data from outside the hospital for validation. Machine learning models have the potential to integrate real-world data and predict VPA concentrations, providing a promising tool for reducing the need for frequent monitoring of serum levels in clinical practice. • Use machine learning to predict serum valproic acid concentration from real-world data. • Models achieved 0.72–0.88 accuracy for various binary and continuous outcomes. • Higher serum albumin is one of the key features influencing higher serum valproic acid concentrations. [ABSTRACT FROM AUTHOR]

Background Persistent Staphylococcus aureus bacteremia is associated with metastatic infection and adverse outcomes, whereas gram-negative bacteremia is normally transient and shorter course therapy is increasingly advocated for affected patients. Whether the prolonged detection of pathogen DNA in blood by culture-independent systems could have prognostic value and guide management decisions is unknown. Methods We performed a multicenter, prospective, observational study on 102 patients with bloodstream infection (BSI) to compare time to bloodstream clearance according to T2 magnetic resonance and blood cultures over a 4-day follow-up. We also explored the association between duration of detectable pathogens according to T2 magnetic resonance (magnetic resonance–DNAemia [MR-DNAemia]) and clinical outcomes. Results Time to bloodstream clearance according to T2 magnetic resonance was significantly longer than blood culture clearance (HR,.54; 95% CI,.39–.75) and did not differ according to the causative pathogen (P =.5). Each additional day of MR-DNAemia increased the odds of persistent infection (defined as metastatic infection or delayed source control) both in the overall population (OR, 1.98; 95% CI, 1.45–2.70) and in S. aureus (OR, 1.92; 95% CI, 1.12–3.29) and gram-negative bacteremia (OR, 2.21; 95% CI, 1.35–3.60). MR-DNAemia duration was also associated with no improvement in Sequential Organ Failure Assessment score at day 7 from infection onset (OR, 1.76; 95% CI, 1.21–2.56). Conclusions T2 magnetic resonance may help diagnose BSI in patients on antimicrobials with negative blood cultures as well as to identify patients with metastatic infection, source control failure, or adverse short-term outcome. Future studies may inform its usefulness within the setting of antimicrobial stewardship programs. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) patients have a higher chance of survival if it is diagnosed at an early stage, which is essential for efficient treatment of the condition. The results of an elevated risk of cancer, including BC, previously associated with the ins/del polymorphism rs145204276 in the promoter region of growth arrest-specific 5 (GAS5) are still up for debate. Thus, this study aimed to appraise the frequency of the GAS5 rs145204276 variant with BC risk and demonstrate the potential impact of the sirtuin 1 (SIRT-1), transforming growth factor-beta (TGF-β), and microRNA-182 (miR-182) expression and their diagnostic value in BC. Methods: Blood samples of 155 patients with BC and fibroadenoma and 80 healthy controls were analyzed for GAS5 rs145204276 single nucleotide polymorphism (SNP), SIRT-1, TGF-β, and miRNA-182 expression levels. Results: Ins/ins genotype and ins allele frequencies for GAS5 rs145204276 were considerably higher in BC patients compared with controls. Patients with BC had significantly greater serum levels of TGF-β, miR-182, and SIRT-1 expression. Conclusions: The SIRT-1, TGF-β, and miR-182 genes provide novel, noninvasive diagnostic biomarkers for BC. [ABSTRACT FROM AUTHOR]

The dream of making a conscious humanoid – whether as servant, guard, entertainer, or simply as testament to human creativity – has long captivated the human imagination. However, while past attempts were performed by magicians and mystics, today scientists and engineers are doing the work to turn myth into reality. This essay introduces the fundamental concepts surrounding human consciousness and machine consciousness and offers a theological contribution. Using the biblical association of the soul to blood, it will be shown that the Bible provides evidence of a scientific claim, while at the same time, science provides evidence of a biblical claim. [ABSTRACT FROM AUTHOR]

Introduction: Mindray MC‐80 is an automated system for digital imaging of white blood cells (WBCs) and their pre‐classification. The objective of this work is to analyse its performance comparing it with the CellaVision® DM9600. Methods: A total of 445 samples were used, 194 normal and 251 abnormal: acute leukaemia (100), myelodysplastic syndromes/myeloproliferative neoplasms (33), lymphoid neoplasms (50), plasma cell neoplasms (14), infections (49) and thrombocytopenia (5). WBC pre‐classification values with the MC‐80 and DM9600 were compared with (1) the microscope, (2) Mindray BC‐6800Plus differentials in only normal samples, and (3) confirmed or reclassified images (post‐classification). Pearson's correlation, Lin's concordance, Passing‐Bablok regression, and Bland–Altman plots were used. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for abnormal cells using the MC‐80 were calculated. Results: The PPV and NPV were above 98% and 99%, for normal samples. For immature granulocytes (IG), NPV and PPV were 100% and 74.2%. When comparing the WBC differentials using the MC‐80, the microscope and the BC‐6800Plus, no differences were found except for basophils and IG. Our results showed good agreement between the pre‐ and post‐classification of normal WBC, including IG, quantified by high correlation and concordance values (0.91–1). Sensitivity and specificity for blasts were 0.984 and 0.640. The MC‐80 detected abnormal lymphocytes in 30% of the smears from patients with lymphoid neoplasm. Plasma cell identification was better using the DM9600. The sensitivity and specificity for erythroblast detection were 1 and 0.890. Conclusion: We found that the MC‐80 shows high performance for WBC differentials for both normal samples and patients with haematological diseases. [ABSTRACT FROM AUTHOR]

Introduction: Circulating microparticles (MP) are being described as potential biomarkers for disease activity in a variety of conditions including sickle cell anemia (SCA). However, relatively little is known about the influence of spleen status on MP levels in patients with SCA. Methods: Using a prospective study design we characterize circulating MP in 144 patients with SCA in steady state by assessing their cellular origin and their relationships to spleen status defined by clinical and imaging findings. In addition, MP levels were studied according to demographic characteristics, clinical status, treatment modalities, and other hematological and biochemical parameters. Absolute plasma concentrations of MP were determined by flow cytometry. Results: Patients with SCA displayed a 10‐fold increase in levels of MP derived from red blood cell (RBC) and platelets (PLT) when compared to their healthy counterparts (p < 0.0001). Splenectomized patients with SCA have more pronounced levels of MPRBC and MPPLT, and remained elevated after several weeks of follow‐up. Levels of MP were not significantly associated with spleen removal procedures, age, gender, clinical severity score, hydroxyurea therapy, hemoglobin F, and co‐existence of glucose‐6‐phosphate dehydrogenase deficiency. Conclusion: Collectively, these results suggest that splenectomy affects circulating levels of MP regardless of the known SCA modifiers and correlates. [ABSTRACT FROM AUTHOR]

The article discusses case studies which show bacteremia and/or fungemia after examining peripheral blood smears, especially in critically ill individuals with non-specific symptoms. The patients studied include a 31-year-old woman who was hospitalized for investigation of coma presented with vaginal bleeding, a 27-year-old man with poor limb movement and limb convulsions for two days, and a 53-year-old male patient with progressively reduced consciousness following head, neck and chest trauma.

The present study employed a randomized crossover design to investigate the effect of strength-training exercise at varying intensities on acute changes in plasma brain-derived neurotrophic factor (BDNF) levels. Fourteen trained male subjects (41.0±5.8 years old) were enrolled in the current study. The strength-training protocol included bench press, leg press, and lat pull-down exercises. Participants performed four sets with repetition failure at 60% or 80% of their one-repetition maximum (1RM), with a two-minute rest period. The order of intensity was randomized among volunteers. Blood samples were collected before, immediately after, and one hour after each exercise protocol. A time-point comparison revealed that a single session of strength training at 60% of 1RM increased lactate plasma concentrations from 1.2 to 16 mmol/L (p<0.0001). However, no significant changes were observed in the plasma BDNF concentration. Conversely, the training session at 80% of 1RM increased lactate concentrations from 1.3 to 14 mmol/L (p<0.0001) and BDNF concentrations from 461 to 1730 pg/ml (p=0.035) one hour after the session's conclusion. These findings support the hypothesis that a single strength-training session at 80% 1RM can significantly enhance circulating levels of BDNF. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to review the blood stream infections of major burn patients in a tertiary care burn unit to determine the most prevalent infecting organisms in order to have a better empirical therapy protocol. Methods: This retrospective study analysed the blood stream infection of 155 major burn (>20% Total Body Surface Area [TBSA]) patients in Khoula Hospital, Muscat, Oman between January 2014 to December 2019. Results: The median age was 33 years and 57.42% of patients were male. The median TBSA was 38%, mortality was 25.16% and 50.9% of patients had positive blood cultures. The expired patients had higher TBSAs, Abbreviated Burns Severity Index scores and earlier first positive blood cultures. Candida was commonly grown in all the blood cultures, but the most prevalent organisms were Acinetobacter, Staphylococci, Klebsiella, Enterococcus and Pseudomonas. All Acinetobacter species are multidrug resistant. Of the 17 patients who had Kelbsiella grown in the blood culture, 8 grew multidrug-resistant Klebsiella. Only 4 patients' blood cultures grew methicillin-resistant Staphylococcus aureus. The number of blood culture samples taken ranged between 1-28 (median = 6). The first positive blood culture showed that Staphylococcus epidermidis and Acinetobacter were the most common infecting organisms. Conclusions: Multidrug-resistant Acinetobacter was the most predominant microorganism grown from the blood cultures of major burn patients in a tertiary care burn unit. Empirical therapy should include antibiotics that are effective against this organism to reduce the mortality. [ABSTRACT FROM AUTHOR]

Increasing studies have investigated inflammatory burden of adults with childhood adversity, but less is known about how childhood maltreatment affects the inflammation level of adolescents. Baseline data of a school cohort of physical and mental health status and life experience survey on primary and secondary school students in Anhui Province, China was used. Childhood maltreatment of children and adolescents was assessed by Chinese version of Childhood Trauma Questionnaire-Short Form (CTQ-SF). Urine samples were collected to assess levels of soluble urokinase Plasminogen Activator Receptor (suPAR), C-reactive protein (CRP) and cytokines interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA). Logistic regression was conducted to examine the association between childhood maltreatment exposure and risk of high inflammation burden. A total of 844 students were included with mean age 11.41 ± 1.57 years old. Adolescents with emotional abuse were significantly more likely to have high level of IL-6 (OR = 3.59, 95% CI 1.16–11.14). In addition, adolescents with emotional abuse were more likely to show high IL-6 and high suPAR combination (OR = 33.41, 95% CI 1.69–659.22), and high IL-6 and low CRP combination (OR = 4.34, 95% CI 1.29–14.55). Subgroup analyses showed that emotional abuse was associated with high IL-6 burden among boys or adolescents with depression. Childhood emotional abuse was positively associated with higher burden of IL-6. Early detection and prevention of emotional abuse for children and adolescents, especially for boys or adolescents with depression status, may be helpful for preventing elevated inflammatory burden and related health problems. [ABSTRACT FROM AUTHOR]

Canada has recently invested in the large-scale exploitation of scandium oxide. However, there are no studies available to date to understand its toxicokinetics in the animal or human body, which is necessary to assess exposure and health risks. The aim of this research was to investigate the toxicokinetics of absorbed scandium oxide (Sc 2 O 3) using the rat as an experimental model. Male Sprague-Dawley rats were injected intravenously with 0.3 or 1 mg Sc 2 O 3 /kg body weight (bw). Blood and excreta (urine and feces) were collected sequentially during a 21-day period, and main organs (liver, spleen, lungs, kidneys, brain) were withdrawn at sacrifice on day 21. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for the measurement of Sc element in the different samples. The mean residence time (MRT IV) calculated from the blood profile was 19.7 ± 5.9 h and 43.4 ± 24.6 h at the lower and higher doses, respectively. Highest tissue levels of Sc were found in the lungs and liver; respective lung values of 10.6 ± 6.2% and 3.4 ± 2.3% of the Sc dose were observed at the time of sacrifice while liver levels represented 8.9 ± 6.4% and 4.6 ± 1.1%. Elimination of Sc from the body was not complete after 21 days. Cumulative fecal excretion over the 21-day collection period represented 12.3 ± 1.3% and 5.9 ± 1.0% of the lower and higher Sc doses, respectively, and showed a significant effect of the dose on the excretion; only a small fraction of the Sc dose was recovered in urine (0.025 ± 0.016% and 0.011 ± 0.004% in total, respectively). In addition to an effect of the dose on the toxicokinetics, results highlight the importance of the lung as a site of accumulation and retention of Sc 2 O 3 , which raises the question of the risks of effects related to respiratory exposure in workers. The results also question the relevance of urine as a matrix for biological exposure monitoring. A more in-depth inhalation toxicokinetic study would be necessary. • Intravenously injected scandium oxide accumulates in lungs and liver mainly. • Excretion occurs mainly in feces and little is found in urine. • The dose impacts the toxicokinetics of scandium oxide. • Higher scandium oxide dose resulted in lower cumulative excretion rates. • Lung retention raises the question of risks related to respiratory exposure. [ABSTRACT FROM AUTHOR]

Blood is one of the most commonly found biological fluids at crime scenes, with the detection and identification of blood holding a high degree of evidential value. It can provide not only information about the nature of the crime but can also lead to identification via DNA profiling. Presumptive tests for blood are usually sensitive but not specific, so small amounts of the substrate can be detected, but false-positive results are often encountered, which can be misleading. Novel methods for the detection of red blood cells based on aptamer–target interactions may be able to overcome these issues. Aptamers are single-stranded DNA or RNA sequences capable of undergoing selective antigen association due to three-dimensional structure formation. The use of aptamers as a target-specific moiety poses several advantages and has the potential to replace antibodies within immunoassays. Aptamers are cheaper to produce, display no batch-to-batch variation and can allow for a wide range of chemical modifications. They can help limit cross-reactivity, which is a hindrance to current forensic testing methods. Within this study, a modified Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process was used to generate aptamers against whole red blood cells. Obtained aptamer pools were analysed via massively parallel sequencing to identify viable sequences that demonstrate a high affinity for the target. Using bioinformatics platforms, aptamer candidates were identified via their enrichment profiles. Binding characterisation was also conducted on two selected aptamer candidates via fluorescent microscopy and qPCR to visualise and quantify aptamer binding. The potential for these aptamers is broad as they can be utilised within a range of bioassays for not only forensic applications but also other analytical science and medical applications. Potential future work includes the incorporation of developed aptamers into a biosensing platform that can be used at crime scenes for the real-time detection of human blood. [ABSTRACT FROM AUTHOR]

Background: Tarai buffalo is indigenous buffalo breed of Uttarakhand state, dual purpose, well adapt to hot-humid climatic condition of Tarai area. This study aimed to evaluate the alterations in the hemato-biochemical, endocrine, milk somatic cell count and milk composition in lactating Tarai buffaloes. Methods: Thirty-six healthy Tarai buffaloes were selected from four different Gujjar farms and divided into four groups consisting nine buffaloes in each group as early (60±30 days), mid (120±30 days) and late (180±30 days) lactation stages and dry buffaloes. Both blood and milk samples were collected once from each lactation stage of selected animals. Hematological parameters and milk composition were evaluated by standard procedures and methods. Biochemical and endocrine parameters were evaluated using commercially available kits as per manufacturer's protocol. Milk somatic cell count (SCC) was done by direct microscopic counts using Newman Lampert stain. Result: It observed significantly (p<0.05) higher TLC value but lower plasma glucose, cholesterol, calcium, phosphorus and urea levels during early lactation stage. Significantly (p<0.05) declined in plasma total protein during late lactation stage and triglyceride in dry cows. Plasma hormone significantly (p<0.05) higher in cortisol during early lactation while higher T4 and insulin in late lactation stages. Milk fat, urea and total solids were significantly (p<0.05) decreased during early lactation and again increased during late lactation while milk SCC significantly (p<0.05) higher during early and late lactation stages. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) can lead to higher cellular damage, making cell-free DNA (cfDNA) a potential biomarker for assessing disease severity. The aim of this study is to evaluate survival predictions using cfDNA measurements and assess its correlation with MI. Materials and Methods: A direct fluorescence assay was employed to measure cfDNA content in the blood samples of participants. The inclusion criteria included patients who gave informed consent, suffering from ST-elevation myocardial infraction (STEMI) based on established diagnostic criteria (joint ESC/ACC guidelines), between the age of 18 and 80 years old, and had elevated troponin biomarker levels. The study included 150 patients diagnosed with STEMI and 50 healthy volunteers as controls. Serial monitoring of patients was conducted to track their postdisease status. The rate of change of cfDNA was calculated and daily measurements for 7 days were recorded. Results: Mean levels of cfDNA were found to be 5.93 times higher in patients with STEMI compared to healthy controls, providing clear evidence of a clinical correlation between cfDNA and STEMI. Patients were further categorized based on their survival status within a 90-day period. The study observed a strong predictive relationship between the rate of change of cfDNA during daily measurements and survival outcomes. To assess its predictive capability, a receiver operating characteristics (ROC) curve analysis was performed. The ROC analysis identified an optimal cutoff value of 2.50 for cfDNA, with a sensitivity of 81.5% and specificity of 74.0% in predicting disease outcomes. Conclusion: This study demonstrates a robust association between cfDNA and STEMI, indicating that cfDNA levels can be a valuable early prognostic factor for patients. Serial measurements of cfDNA during early disease onset hold promise as an effective approach for predicting survival outcomes in MI patients. [ABSTRACT FROM AUTHOR]

The article discusses the challenges of diagnosing early-onset sepsis (EOS) in newborns due to nonspecific symptoms, leading to widespread empiric antibiotic use. Topics include the impact of outdated practices, the development and implementation of the NEOS calculator, and the aims and methods of the quality improvement project to decrease EOS evaluations and empiric antibiotic use.

Objective: Although heparin is the current standard anticoagulant during venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO), factors including heparin-induced thrombocytopenia, heparin resistance and drug shortages necessitate alternative anticoagulants such as direct thrombin inhibitors. The aim was to characterize dosing, safety, and efficacy of bivalirudin during ECMO support. Methods: This retrospective single-center study included 24 adults on ECMO support who received ≥6 hours of bivalirudin. The primary endpoint was dose to first therapeutic activated partial thromboplastin time (aPTT). Secondary endpoints included evaluating dosing between ECMO modes, incidence of bleeding and thrombotic events, and time in therapeutic range (TTR). Results: The dose at time of first therapeutic aPTT was bivalirudin 0.05 [0.05-0.1] mg/kg/hour. Bivalirudin dosing requirements were lower in VAECMO compared to VV-ECMO patients and were not impacted by continuous venovenous hemofiltration. Time to therapeutic aPTT was 5.5 [2-13] hours for VA-ECMO and 4.5 [2-8.6] hours for VV-ECMO patients. During any mode of ECMO TTR was 58.3% [39.6-73.1]. Thrombotic events occurred in 3 (13%) patients and major bleeding occurred in 12 (50%) patients. Conclusions: Our findings demonstrated variable bivalirudin dosing requirements based on mode of ECMO and dosing modifications may not be required during CVVH. Factors including mode of ECMO, indication for bivalirudin and concomitant antiplatelet therapy may impact hematologic events. Application of this data can assist with developing a bivalirudin ECMO protocol which provides less variability in initial dosing and TTR. [ABSTRACT FROM AUTHOR]

Background: There is an unmet need in amyotrophic lateral sclerosis (ALS) to provide specific biomarkers for the disease. Due to their easy availability, we aimed to investigate whether routine blood parameters provide useful clues for phenotypic classification and disease prognosis. Methods: We analyzed a large inpatient cohort of 836 ALS patients who underwent deep phenotyping with evaluation of the clinical and neurophysiological burden of upper (UMN) and lower (LMN) motor neuron signs. Disability and progression rate were measured through the revised ALS Functional Rating Scale (ALSFRS-R) and its changes during time. Cox regression analysis was performed to assess survival associations. Results: Creatinine significantly correlated with LMN damage (r = 0.38), active (r = 0.18) and chronic (r = 0.24) denervation and baseline ALSFRS-R (r = 0.33). Creatine kinase (CK), alanine (ALT) and aspartate (AST) transaminases correlated with active (r = 0.35, r = 0.27, r = 0.24) and chronic (r = 0.37, r = 0.20, r = 0.19) denervation, while albumin and C-reactive protein significantly correlated with LMN score (r = 0.20 and r = 0.17). Disease progression rate showed correlations with chloride (r = −0.19) and potassium levels (r = −0.16). After adjustment for known prognostic factors, total protein [HR 0.70 (95% CI 0.57–0.86)], creatinine [HR 0.86 (95% CI 0.81–0.92)], chloride [HR 0.95 (95% CI 0.92–0.99)], lactate dehydrogenase [HR 0.99 (95% CI 0.99–0.99)], and AST [HR 1.02 (95% CI 1.01–1.02)] were independently associated with survival. Conclusions: Creatinine is a reliable biomarker for ALS, associated with clinical features, disability and survival. Markers of nutrition/inflammation may offer additional prognostic information and partially correlate with clinical features. AST and chloride could further assist in predicting progression rate and survival. [ABSTRACT FROM AUTHOR]

The objective of this study was to characterize changes in the serum metabolome and various indicators of oxidative balance in dairy cows starting 2 wk before dry-off and continuing until wk 16 of lactation. Twelve Holstein dairy cows (body weight 745 ± 71 kg, body condition score 3.43 ± 0.66; mean ± SD) were housed in a tiestall barn from 10 wk before to 16 wk after parturition. Cows were dried off 6 wk before the expected calving date (mean dry period length = 42 d). From 8 wk before calving to 16 wk after calving, blood samples were taken weekly to study redox metabolism by determining antioxidant capacity, measured as the ferric-reducing ability of plasma, reactive oxidative metabolites, oxidative stress index, oxidative damage of lipids, measured as thiobarbituric acid reactive substances, and glutathione peroxidase activity. According to these results, dairy cows had the lowest serum antioxidant capacity and greater levels of oxidative stress during the dry-off period and the early postpartum period. For metabolomics, a subset of serum samples including wk −7 (before dry-off), −5 (after dry-off), −1, 1, 5, 10, and 15 relative to calving were used. A targeted metabolomics approach was performed using liquid chromatography and flow injection with electrospray ionization triple quadrupole mass spectrometry using the MxP Quant 500 kit (Biocrates Life Sciences AG). A total of 240 metabolites in serum were used in the final data analysis. Principal component analysis revealed a clear separation by days of sampling, indicating a remarkable shift in metabolic phenotype between the dry period and late and early lactation. Changes in many non-lipid metabolites associated with one-carbon metabolism, the tricarboxylic acid cycle, the urea cycle, and AA catabolism were observed in the study, with changes in AA serum concentrations likely related to factors such as energy and nitrogen balance, digestive efficiency, and changing diets. The study confirmed an extensive remodeling of the serum lipidome in peripartum dairy cows, highlighting the importance of changes in acylcarnitine (acylCN), phosphatidylcholines (PC), and triacylglycerols (TG), as they play a crucial role in lipid metabolism. Results showed that short-chain acylCN increased after dry-off and decreased thereafter, whereas lipid-derived acylCN increased around parturition, suggesting that more fatty acids could enter mitochondria. Phospholipids and sphingolipids in serum showed changes during lactation. In particular, concentrations of sphingomyelins, PC, and lysoPC decreased around calving but increased in mid- and late lactation. In contrast, concentrations of TG remained consistently low after parturition. The serum concentrations of bile acids fluctuated during the dry period and lactation, with glycocholic acid, cholic acid, glycodeoxycholic acid, and taurocholic acid showing the greatest concentrations. These changes are likely due to the interplay of diet, liver function, and the ability of the gut microbiota to convert primary to secondary bile acids. Overall, these descriptive results may aid in hypothesis generation and in the design and interpretation of future metabolite-based studies in dairy cows. Furthermore, they contribute to our understanding of the physiological ranges in serum metabolites relative to the lactation cycle of the dairy cow. [ABSTRACT FROM AUTHOR]