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The larval excretions/secretions (ES) of blowflies contain proteolytic enzymes and bacteria that assist with tissue breakdown. Decomposition fluid (DF) contains organic and inorganic waste products from cell death. This study investigated if human DNA recovery from blood was impacted by exposure to ES and DF over time. Lucilia sericata ES were collected daily from 50 larvae, and all available DF was collected from two fetal piglets left to decompose for 2 weeks. Daily for 3–5 days, 28 μL‐30 μL of ES, DF, or a 1:1 mixture of the fluids was added to 30 μL of blood on cotton. Three bloodstains per treatment were sampled every 12 h up to 3 days and at 1 and 2 weeks after initial addition of fluid. No PCR inhibition was detected, but DNA degradation increased over time, primarily in samples exposed to ES and ES/DF mixtures. The amount of DNA recovered decreased over time, but generally more DNA was recovered from DF samples than other samples. Full profiles, or partial profiles suitable for routine database searching (14–39 alleles), were generated from all DF and ES samples and at least one mixture sample at all timepoints. Partial profiles of between 1 and 13 alleles were obtained from all other mixture samples, except one mixture sample which generated no profile. These findings indicate bloodstain evidence recovered from maggot‐infested and/or decomposing bodies may generate forensically useful DNA evidence and should be analyzed as quickly as possible after collection or stored appropriately to prevent further degradation. [ABSTRACT FROM AUTHOR]

Background Methods and Results Conclusions Allogeneic hematopoietic cell transplantation remains limited when stem cell registrants cannot be contacted, are not medically fit, are unavailable, or unwilling to proceed. In a recent report, registrants who were prior blood donors were more likely to be available for donation. In this study, we analyzed extent to which recruiting blood donors to the Canadian Blood Services Stem Cell Registry (CBS SCR) can meet targets for ethnic diversity, age, and proximity to collection facilities.We analyzed 124,496 active blood donors on July 1, 2023 regarding the criteria for recruitment to the CBS SCR. A total of 40,518 (32%) were younger than 36 years of age and 49% were first‐time donors (potential new recruits year over year). The ethnicity of blood donors younger than 36 years aligns more closely with the 2021 Canadian census compared to stem cell donors who were also previous blood donors, and to the current total inventory of all registrants on the CBS SCR. Of the blood donors, certain ethnic groups, including Black, Chinese, and First Nations/Indigenous, remain underrepresented. A greater proportion of active whole blood donors live within 400 km of a stem cell collection center (91%) compared to stem cell donors who donated during the past 10 years (80%).Recruitment of blood donors offers an opportunity to improve the ethnic diversity of the CBS SCR and increase proximity of registrants to stem cell collection centers. The potential improved availability of registrants when matched to patients requires confirmation. [ABSTRACT FROM AUTHOR]

Sinusoidal obstruction syndrome/veno‐occlusive disease (SOS/VOD) is a life‐threatening complication which can develop after haemopoietic stem cell transplantation (HSCT) and some antibody–drug conjugates. Several SOS/VOD diagnostic and management guidelines exist, with the most recent and refined being the European Society for Blood and Marrow Transplantation adult and paediatric guidelines. Timely diagnosis and effective management (including the availability of therapeutic options) significantly contribute to improved patient outcomes. In Australia and New Zealand, there is variability in clinical practice and access to SOS/VOD therapies. This review aims to summarise the current evidence for SOS/VOD diagnosis, prevention and treatment and to provide recommendations for SOS/VOD in the context of contemporary Australasian HSCT clinical practice. [ABSTRACT FROM AUTHOR]

Background: Pauci‐immune glomerulonephritis (GN) due to antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a common cause of crescentic GN. Despite advances in treatment, rates of mortality and progression to end‐stage kidney disease remain high. Renal involvement is diagnosed by histological examination of kidney tissue. Serum ANCAs play a significant role in AAV; however, the value of serum ANCA quantification to predict renal involvement is not well‐established. Aim: We aimed to evaluate the diagnostic accuracy of serum ANCA titres in diagnosing AAV with renal involvement. Methods: We conducted a retrospective study of consecutive native kidney biopsies reported at our centre from 2016 to 2021. We included all adults who had both a kidney biopsy and ANCA serology. ANCA serology was tested using indirect immunofluorescence with reporting of titres. Antibodies to proteinase 3 and myeloperoxidase were measured using a chemiluminescent immunoassay. Results: Eight hundred and forty‐eight native kidney biopsies were reported during the study period. Five hundred and seven cases were included. The biopsy prevalence of pauci‐immune GN in paired samples was 41/507 (8.1%). Most of the cohort had haematuria (66.6%), proteinuria (93.4%) and/or acute kidney injury (65.0%). A positive ANCA at any titre demonstrated a sensitivity of 97.6% and a specificity of 71.2% for a diagnosis of pauci‐immune GN. The area under the curve for the receiver operator characteristic was 0.93 (95% confidence interval [CI]: 0.89–0.97). A cutoff ANCA titre of 1:160 provided the optimum balance between a sensitivity of 75.6% (95% CI: 59.7%–87.6%) and a specificity of 94.0% (95% CI: 91.6%–96.0%). Conclusions: ANCA titres are highly predictive of pauci‐immune GN in the appropriate context. While serum ANCA quantitation may not replace renal biopsy, reporting will assist in the decision to start treatment early for patients with organ or life‐threatening disease. [ABSTRACT FROM AUTHOR]

This research aims to examine the impact of programmed cell death 4 (PDCD4), microRNA‐21 (miR‐21) and microRNA‐208a (miR‐208a) transcripts, and protein levels on oral epithelial dysplasia (OED) development in oral squamous cell carcinoma (OSCC). Methods: The research investigation involved the collection of saliva, blood, and tissue samples from a total of 20 patients diagnosed with OSCC, 15 patients diagnosed with OED, and 15 healthy individuals. PDCD4, miR‐21, and miR‐208a expression was performed by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). PDCD4 protein levels were assessed using enzyme‐linked immunosorbent assay (ELISA) in both saliva and blood samples. For statistical analysis, the Kruskal–Wallis test and the Spearmen rank test were utilised. Results: PDCD4 expression levels were considerably lower in patients with OSCC and OED (p < 0.05) in three biological samples. In contrast, miR‐21 expression was higher in OED and OSCC patients. Patients with low PDCD4 mRNA levels and strong miR‐21 expression had a significant connection (p < 0.05) with tumor size and depth. Conclusions: Examining PDCD4 and miR‐21 transcript levels may help detect the transition from OED to OSCC. This work suggests that PDCD4 and miR‐21 expression levels in liquid biopsies may be biomarkers for OED monitoring in the future. [ABSTRACT FROM AUTHOR]

Background: Persistent inflammation is associated with adverse health outcomes, but its impact on mortality has not been investigated previously among hip fracture patients. This article aims to investigate the influence of changes in levels of cytokines in the 2 months after a hip fracture repair on 5‐year mortality. Methods: This is a prospective cohort study from the Baltimore Hip Studies (BHS) with 191 community‐dwelling older men and women (≥65 years) who had recently undergone surgical repair of an acute hip fracture, with recruitment from May 2006 to June 2011. Plasma interleukin‐6 (IL‐6), soluble tumor necrosis factor alpha receptor1 (sTNFα‐R1), and interleukin‐1 receptor agonist (IL‐1RA) were obtained within 22 days of admission and at 2 months. All‐cause mortality over 5 years was determined. Logistic regression analysis tested the associations between the cytokines' trajectories and mortality over 5 years, adjusted for covariates (age, sex, education, body mass index, lower extremity physical activities of daily living, and Charlson comorbidity index). Results: High levels of IL‐6 and sTNFα‐R1 at baseline with small or no decline at 2 months were associated with higher odds of 5‐year mortality compared with those with lower levels at baseline and greater decline at 2 months after adjustment for age, and other potential confounders (OR = 4.71, p = 0.01 for IL‐6; OR = 15.03, p = 0.002 for sTNFα‐R1). Similar results that failed to reach significance were found for IL‐1RA (OR = 2.40, p = 0.18). Those with higher levels of cytokines at baseline with greater decline did not have significantly greater mortality than the reference group, those with lower levels at baseline and greater decline. Conclusion: Persistent elevation of plasma IL‐6 and sTNFα‐R1 levels within the first 2 months after hospital admission in patients with hip fracture is associated with higher 5‐year mortality. These patients may benefit from enhanced care and earlier intensive interventions to reduce the risk of death. [ABSTRACT FROM AUTHOR]

Summary: Objective: Children with overweight/obesity (OW/OB) exhibit poor cardiometabolic health, yet mechanisms influencing brain health remain unclear. We examined the differences in neurological‐related circulating proteins in plasma among children with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) and the association with metabolic syndrome markers. Methods: In this cross‐sectional study, we included 84 Caucasian children (39% girls), aged 10.1 ± 1.1 years, from the ActiveBrains project (NCT02295072). A ninety‐two‐protein targeted approach using Olink's® technology was used. Results: We identified distinct concentrations of CD38, LAIR2, MANF and NRP2 proteins in MHO compared with MUO. Moreover, individual metabolic syndrome (MS) markers were linked to nine proteins (CD38, CPM, EDA2R, IL12, JAMB, KYNU, LAYN, MSR1 and SMOC2) in children with OW/OB. These proteins play crucial roles in diverse biological processes (e.g., angiogenesis, cholesterol transport, nicotinamide adenine dinucleotide (NAD+) catalysis and maintenance of blood–brain barrier) related to brain health. Conclusion: Our proteomics study suggests that cardiometabolic health (represented by MHO/MUO or individual MS markers) is associated with the concentration in plasma of several proteins involved in brain health. Larger‐scale studies are needed to contrast/confirm these findings, with CD38 standing out as a particularly noteworthy and robust discovery. [ABSTRACT FROM AUTHOR]

Background: The distribution and elimination of infused crystalloid fluid is known to be affected by general anesthesia, but it is unclear whether changes differ depending on whether the patient is operated in the flat recumbent position, the Trendelenburg ("legs up") position, or the reverse Trendelenburg ("head up") position. Methods: Retrospective data on hemodilution and urine output obtained during and after infusion of 1–2 L of Ringer's solution over 30–60 min were collected from 61 patients undergoing surgery under general anesthesia and 106 volunteers matched with respect to the infusion volume and infusion time. Parameters describing fluid distribution in the anesthetized and awake subjects were compared by population volume kinetic analysis. Results: General anesthesia decreased the rate constant for urine output by 79% (flat recumbent), 91% (legs up) and 91% (head up), suggesting that laparoscopic surgery per se intensified the already strong anesthesia‐induced fluid retention. General anesthesia also decreased the rate constant governing the return of the distributed fluid to the plasma by 32%, 15%, and 70%, respectively. These results agree with laboratory data showing a depressive effect of anesthetic drugs on lymphatic pumping, and further suggest that the "legs up" position facilitates lymphatic flow, whereas the "head up" position slows this flow. Both Trendelenburg positions increased swelling of the "third fluid space". Conclusions: General anesthesia caused retention of infused fluid with preferential distribution to the extravascular space. Both Trendelenburg positions had a modifying influence on the kinetic adaptations that agreed with the gravitational forces inflicted by tilting to body. [ABSTRACT FROM AUTHOR]

Background: The Sysmex XN‐V is derived from the new Sysmex XN series of human hematology analyzers. The main changes from the previously validated XT‐2000iV analyzer include an optic‐fluorescent analysis for platelets and a nucleated red blood cell (NRBC) count. Objective: We aimed to validate the Sysmex XN‐V for feline blood following the American College for Veterinary Clinical Pathology and International Council for Standardization in Hematology recommendations. Methods: Feline EDTA blood specimens were analyzed on the Sysmex XN‐V to evaluate repeatability, linearity, comparison with the XT‐2000iV analyzer and manual methods, stability, and to verify the previously established Sysmex XT‐2000iV RIs. Results: Repeatability was excellent for most variables. Visually determined linearity was excellent or good for most variables except eosinophils and platelet variables. The correlation between the XN‐V and XT‐2000iV analyzers was good (≥0.82) for all variables except reticulocyte indices. Correlations between the Sysmex XN‐V and manual differential counts were good to excellent for most variables, acceptable for neutrophils, and fair for monocytes and NRBC. The previously established Sysmex XT‐2000iV RIs can be used to interpret results from the Sysmex XN‐V analyzer for most variables except red cell distribution width and reticulocyte variables. The RI for platelet variables could not be evaluated because of platelet clumps. Changes in the Sysmex XN‐V measurements after storage at 4 and 24°C were similar to those described for the Sysmex XT‐2000iV analyzer. Conclusions: The performance of the Sysmex XN‐V analyzer was good and compared favorably with the Sysmex XT‐2000iV analyzer. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of asthma and chronic obstructive pulmonary disease (COPD) becomes difficult in a primary healthcare center due to ambiguous interpretation of spirometry and lack of facility to access established biomarkers. While routine hematological indices are easily available and accessible. The study aimed to evaluate the role of different hemogram indexes in males in COPD, asthma, and healthy smokers. Materials and Methods: Lung function tests and complete blood count (CBC) were done for 50 male subjects each from asthma, COPD, and healthy smokers. Multivariate analysis (MVA) was performed on blood indices data set. Receiver operating characteristic (ROC) curve was plotted to observe the performance of indexes. Pearson correlation was used to establish association between the lung function and blood indices. Results: Most of the indices were elevated in COPD. Whereas, asthma patients showed a significant increase in eosinophil basophil ratio (EBR), lymphocyte‐monocyte ratio (LMR), and mean platelet volume‐platelet count ratio (MPR). Orthogonal (O)‐ Partial Least‐Squares Discriminant Analysis (PLSDA) and variable importance in projection (VIP) score established EBR, neutrophil‐lymphocyte ratio (NLR) and LMR, as discriminants for asthma. Whereas, Systemic Inflammatory Response Index (SIRI), NLR and EBR were the key variables for COPD. NLR (r = −0.73, p < 0.001) and SIRI (r = −0.71, p < 0.001) were found to be negatively correlated with forced expiratory volume in 1 s (FEV1) percentage of the predicted value (%pred) in asthma and COPD, respectively. EBR showed the sensitivity and specificity of 96% and 86% respectively in asthma. NLR was having sensitivity of 82% and 90% specificity in COPD. Conclusion: Our study in males shows routine hematological indices as being cost‐effective, feasible, and seem to have tremendous potential as screening markers among chronic respiratory diseases in a primary healthcare center. [ABSTRACT FROM AUTHOR]

Purpose: The primary aims of this study were to examine the effects of 9 weeks of aerobic training, comprising three 30‐min sessions per week, on V̇O2max, inhibitory control, and plasma brain‐derived neurotrophic factor (BDNF) levels among adolescents aged 16–19 years. Methods: One hundred twenty‐one untrained or recreationally active adolescents from a Danish high school were enrolled in the study, with 58 females (17.8 ± 0.8 years) and 27 males (18.0 ± 0.9 years) completing it. Participants were randomly divided into three groups performing aerobic training at either moderate‐intensity (MIT: 60%–70% heart rate reserve [HRR]) or high‐intensity (HIT: 80%–100% HRR) or a passive control group (CON) continuing their habitual lifestyle. Both the training groups exercised for 3×30 min per week for 9 weeks using a combination of cycling and running. Before and after the intervention period maximal oxygen uptake (V̇O2max) and the primary outcomes (inhibitory control measured by a modified flanker task, and resting plasma levels of BDNF) were evaluated. Results: After the intervention period, the HIT group demonstrated a larger increase in V̇O2max compared to both the CON and MIT groups, while no significant effects were observed on inhibitory control or plasma BDNF levels in any training group. However, compared to the CON group, the HIT group exhibited a tendency for greater improvement in the flanker interference score (accuracy), attributable to enhanced accuracy on the incongruent stimuli from pre to post. Conclusion: Aerobic training in adolescents increased cardiorespiratory fitness in an intensity‐dependent manner, but no clear effects were observed on neither inhibitory control nor resting plasma BDNF levels. Clinical Trial Registration: ClinicalTrials.gov: NCT02075944. [ABSTRACT FROM AUTHOR]

Combat sports athletes often undergo rapid body mass loss (BML), which presents health risks. Hydration testing has been proposed as a possible solution to reduce or eliminate rapid BML. However, combat sports athletes may exhibit distinct physiological characteristics due to repeated exposure to BML. Thus, traditional and emerging hydration biomarkers should be investigated to determine their potential suitability for field use in this cohort. This study examined whether BML can explain changes in serum and urine osmolality (SosmΔ, UosmΔ), tear osmolarity (TosmΔ), hematocrit (HctΔ), and urine‐specific gravity (USGΔ) after mild–moderate passive dehydration. Biomarker reliability was also assessed across two trials. Fifteen male and female combat sports athletes (age: 26.3 ± 5.3 years, body mass: 67.7 ± 9.9 kg) underwent a sauna protocol twice (5–28 days apart) aiming for 4% BML. The average BML in Trials 1 and 2 was 3.0 ± 0.7%. Regression analysis revealed that BML explained HctΔ (R2 = 0.22, p = 0.009) but not SosmΔ (R2 = 0.11, p = 0.079) or other biomarkers. Intraclass correlation coefficients (ICCs) were significant for all biomarkers except TosmΔ (ICC = 0.06, p = 0.37) and post‐Tosm (ICC = 0.04, p = 0.42); post‐Hct performed best (ICC = 0.82, p < 0.001). Contingency tables with post‐Sosm (295 mOsm/kg) and post‐USG (1.020) cutoffs revealed an 80% true negative rate (TNR) and a 62% true positive rate (TPR). Increasing the Sosm cutoff to 301 mOsm/kg decreased the TNR to 52% but increased the TPR to 83%. Although blood parameters were most sensitive to BML, they could only explain 11%–22% of biomarker variation. The typical USG cutoff misclassified 42% of athletes postdehydration, and reliability was generally poor‐moderate. Alternative strategies should be pursued to manage rapid BML in combat sports. [ABSTRACT FROM AUTHOR]

Gefapixant (MK‐7264, RO4926219, AF‐219) is a first‐in‐class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single‐ and multiple‐dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single‐dose administration of 10‐450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter‐subject variability and a dose‐proportional exposure. Following administration of multiple doses twice daily, the plasma exposures were dose‐proportional at doses ranging from 7.5 to 50 mg and less than dose‐proportional at doses ranging from 100 to 1800 mg. The time to mean peak drug concentration ranged from 2 to 3 h post‐dose, and steady state was achieved by 7 days after dosing, with an accumulation ratio of approximately 2, comparing data from day 1 to steady state. The mean apparent terminal half‐life ranged from 8.2 to 9.6 h. Gefapixant was primarily excreted unmodified in urine. Gefapixant was well tolerated following single‐dose administration up to 1800 mg and multiple doses up to 1800 mg twice daily; there were no serious adverse events (AEs) reported. The most common AE reported was dysgeusia. The PK profile supports a twice‐daily dosing regimen. [ABSTRACT FROM AUTHOR]

The steroid module of the Athlete Biological Passport (ABP) is based on the analysis of six endogenous steroids in urine samples and a Bayesian statistical approach. However, the urinary steroid concentrations may be affected by confounders like microbial degradation, possible co‐administration of diuretics as masking agents, insufficient conjugate hydrolysis or UGT2B17 gene polymorphisms affecting glucuronidation. Therefore, it can be helpful to use other matrices (ABP blood and serum samples) to quantify steroids and thereby support noticeable deviations in the Athlete Biological Passport, for example, abnormally increased urinary testosterone/epitestosterone (T/E) ratios. Aim of the study was to investigate the feasibility to re‐use plasma obtained from athlete ABP blood samples for measuring a steroid profile. Therefore, testosterone, androstenedione, cortisol and cortisone were quantified in 36 intra‐individual matching ABP blood and serum samples. The steroid levels measured in both matrices showed a high agreement indicating a good stability uninfluenced by storage temperature and duration. Our results pointed out the possibility to expand the athlete ABP blood analysis for steroid profiling. [ABSTRACT FROM AUTHOR]

Benzodiazepines are essential screening targets for common sleeping and sedative drugs used in forensic toxicology. Direct analysis in real‐time tandem mass spectrometry was used to rapidly identify 10 benzodiazepines and related metabolites in the blood and urine. The related direct analysis in real‐time tandem mass spectrometry parameters were optimized. A liquid–liquid extraction method using ethyl acetate as the extraction solvent was used for sample preparation. The established method was validated and tested on case specimens. The limits of detection of this method ranged from 0.2 to 20 ng/mL and the limits of quantification from 1 to 50 ng/mL. The recoveries ranged from 78.8% to 114%, and the matrix effects were in the range of −21.2% to 17.9%. The precision and repeatability at high and medium concentrations did not exceed 14.6%, and the limit of quantification did not exceed 18.2%, indicating a desirable linear relationship. The established method was used to determine blood and urine specimens from authentic cases, and promising results were obtained. [ABSTRACT FROM AUTHOR]

Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case–control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non‐DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real‐time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the levels of serum, gingival crevicular fluid (GCF), and salivary adipokines and their possible relationship with periodontitis and obesity. An electronic search was conducted in the following databases: PubMed/ Medline, Scopus, and EBSCOhost through February 2023. Two independent reviewers screened the titles, abstracts, and full text of all the studies. Studies comparing the levels of adipokines in GCF, serum, and/or saliva in subjects with obesity and periodontitis (group 1), subjects with normal weight and periodontitis (group 2), and subjects with obesity and gingival health (group 3) were included. Meta‐analyses and meta‐regression were performed on the data from included studies. Seventeen studies with study participants ranging from 30 to 120 were included with subjects in each group ranging from 10 to 40. There was a significant increase in levels of serum TNF‐α, leptin, IL‐6, and CRP between groups 1 and 2 (p <.05). In GCF, TNF‐α and resistin levels were significantly higher (p <.05) in Group 1 vs. 2. Serum level of leptin was higher for group 1 vs. 3 (p <.05). Meta‐regression analysis revealed that the obesity definition (body mass index (BMI) cut‐off value >25 or >30) was significant for serum resistin (p <.05) and GCF resistin (p <.05) between group 1 and 2. The current analysis indicates that both periodontitis and obesity can modulate the pro‐inflammatory cytokines at systemic and local levels. This bidirectional interaction of periodontitis and obesity via the inflammation pathway seems likely plausible. Further studies are required to elucidate this mechanism in more detail. [ABSTRACT FROM AUTHOR]

Objectives: The inner mechanism of how diabetes affects dental pulp of patients with periodontitis has seldom been reported. We collected clinical samples and explored the influence of diabetes and periodontitis on the pathological change of dental pulp. Methods: Dental pulp from healthy individuals and patients with periodontitis with or without diabetes were collected based on strict inclusion and exclusion criteria. Dental pulp was morphologically observed; advanced glycation end products (AGEs) and lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX1) were examined. Oxidative stress (OS), inflammatory indices, and apoptotic levels were assessed. Results: Morphologically, fibrous structure in the dental pulp of patients with diabetic periodontitis (DP) group was sparse and disordered, and the blood vessel wall was thickened. Diabetes related indexes as AGEs and LOX1 were upregulated. Superoxide dismutase 2 expression was decreased, and OS level was increased. Matrix metalloproteinase 3 and other relevant proinflammatory cytokines levels were increased. The elevated OS and inflammation contributed to upregulation of apoptotic levels in DP group. Conclusions: Diabetes aggravates the pathological changes in the dental pulp of periodontitis patients possibly due to upregulated AGEs and LOX1. Our results highlight the importance of early oral intervention in patients with DP. [ABSTRACT FROM AUTHOR]

This technical note reviews the plethora of concentration units used to report blood‐alcohol concentration (BAC) and breath‐alcohol concentrations (BrAC) for legal purposes in different countries. The choice of units sometimes causes confusion when scientific papers originating from a certain country might be introduced into evidence via expert testimony, such as when alcohol‐related crimes are prosecuted. The concentration units are also important to consider when blood/breath ratios (BBRs) of alcohol are calculated and compared between countries. Statutory BAC limits for driving in most nations are reported in mass/volume (m/v) units, such as g/100 mL (g%) in the United States, mg/100 mL (mg%) in the United Kingdom and Republic of Ireland, or g/L (mg/mL) in many EU nations. By contrast, Germany and the Nordic countries report BAC as mass/mass (m/m) units, hence g/kg or mg/g, which are ~5.5% lower than m/v units, because whole blood has an average density of 1.055 g/mL. There are historical reasons for reporting BAC in mass/mass units because the aliquots of blood analyzed were measured by weight rather than volume. The difference between m/m and m/v is also important in postmortem toxicology, such as when distribution ratios of ethanol between blood and other biological specimens, such as urine, vitreous humor, and cerebrospinal fluid, are reported. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Brain‐derived extracellular vesicles (BEVs) in blood allows for minimally‐invasive investigations of central nervous system (CNS) ‐specific markers of age‐related neurodegenerative diseases (NDDs). Polymer‐based EV‐ and immunoprecipitation (IP)‐based BEV‐enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS‐specificity of proteins associated with these protocols. METHODS: NDD articles investigating BEVs in blood using polymer‐based and/or IP‐based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV‐enrichment and/or post‐enrichment were assessed for CNS‐ and brain‐cell‐type‐specificity, extracellular domains (ECD+), and presence in EV‐databases. RESULTS: A total of 82.1% of studies used polymer‐based (ExoQuick) EV‐enrichment, and 92.3% used L1CAM for IP‐based BEV‐enrichment. Centrifugation times differed across studies. A total of 26.8% of 82 proteins systematically identified were CNS‐specific: 50% ECD+, 77.3% were listed in EV‐databases. CONCLUSIONS: We identified protocol steps requiring standardization, and recommend additional CNS‐specific proteins that can be used for BEV‐enrichment or as BEV‐biomarkers. Highlights: Across NDDs, we identified protocols commonly used for EV/BEV enrichment from blood.We identified protocol steps showing variability that require harmonization.We assessed CNS‐specificity of proteins used for BEV‐enrichment or found in BEV cargo.CNS‐specific EV proteins with ECD+ or without were identified.We recommend evaluation of blood‐BEV enrichment using these additional ECD+ proteins. [ABSTRACT FROM AUTHOR]

Synucleinopathies such as Parkinson's disease (PD) are defined by the accumulation and aggregation of the α-synuclein protein in neurons, glia and other tissues. We have previously shown that destabilization of α-synuclein tetramers is associated with familial PD due to SNCA mutations and demonstrated brain-region specific alterations of α-synuclein multimers in sporadic PD patients following the classical Braak spreading theory. In this study, we assessed relative levels of disordered and higher-ordered multimeric forms of cytosolic α-synuclein in blood from familial PD with G51D mutations and sporadic PD patients. We used an adapted in vitro-cross-linking protocol for human EDTA-whole blood. The relative levels of higher-ordered α-synuclein tetramers were diminished in blood from familial PD and sporadic PD patients compared to controls. Interestingly, the relative amount of α-synuclein tetramers was already decreased in asymptomatic G51D carriers, supporting the hypothesis that α-synuclein multimer destabilization precedes the development of clinical PD. Our data, therefore suggest that measuring α-synuclein tetramers in blood may have potential as a facile biomarker assay for early detection and quantitative tracking of PD progression. Synopsis: The α-synuclein protein exists in different structural forms primarily as monomers, dimers, and tetramers in different human tissues. In the brain, α-synuclein tetramer to monomer ratios are observed to be altered in sporadic Parkinson's disease (sPD) and dementia with Lewy bodies (DLB). Chemical cross-linking using disuccinimidyl glutarate (DSG) and glutaraldehyde (GA), is used to stabilize α-synuclein tetramers in blood. The α-synuclein tetramer to monomer ratio is analyzed via SDS-Page and Western blotting. The α-synuclein tetramer to monomer ratios are altered in blood from sPD patients and patients with G51D α-synuclein mutations. This alteration is characterized by a reduction in tetramer to monomer ratios, indicating a disruption in the regular levels between these two physiological forms of α-synuclein. The α-synuclein protein exists in different structural forms primarily as monomers, dimers, and tetramers in different human tissues. In the brain and blood, α-synuclein tetramer to monomer ratios are observed to be altered in sporadic and familial Parkinson's disease (sPD), and dementia with Lewy bodies (DLB). [ABSTRACT FROM AUTHOR]

Aim: The serum creatinine/cystatin C ratio (CCR) or sarcopenia index is considered a useful marker of muscle mass. However, its usefulness in late‐stage older adults remains unclear. We aimed to determine the usefulness of CCR as an indicator of sarcopenia in community‐dwelling Japanese adults aged >75 years. Methods: Our study recruited participants aged 70, 80, and 90 ± 1 years during the baseline years, and included a 3‐year follow‐up in the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians study. From 2015 to 2018, 955 participants were eligible: 367 in their 70s, 304 in their 80s, and 284 in their 90s. The diagnostic components of sarcopenia, including "low muscle mass, plus low muscle strength, and/or low physical performance," were evaluated using the bioelectrical impedance analysis‐measured skeletal muscle mass index (SMI), handgrip strength, and short physical performance battery (SPPB) score, respectively, in accordance with the Asia Working Group for Sarcopenia 2019 criteria. Separate analyses were performed between each component and CCR, adjusting for sex, body mass index, and other blood biomarkers in each group. Results: The relationship between CCR and sarcopenia components was significant for handgrip strength (β = 0.21, 0.13, 0.19, and P < 0.0001, =0.0088, <0.0001, for the 70s, 80s, and 90s age groups, respectively); however, it was limited for SMI (β = 0.14; P = 0.0022, only for the 90s) and not significant for the SPPB score. Conclusion: CCR is a limited indicator of sarcopenia in late‐stage older adults. Although its association with muscle strength was significant, its relationship with muscle mass and physical performance was less pronounced. Geriatr Gerontol Int 2024; 24: 529–536. [ABSTRACT FROM AUTHOR]

A 6-year-old spayed female Scottish Fold cat presented with lethargy and anorexia. A complete blood cell count indicated severe anemia and mild thrombocytopenia. Examination of peripheral blood smears revealed marked changes in the erythroid lineage, including the presence of basophilic stippling and Howell-Jolly bodies as well as an increase in nucleated erythrocytes, polychromatophils, ovalocytes, and schistocytes. Additionally, some erythrocytes contained a ring or figure-eight shaped structure known as a Cabot ring, which were especially observed in polychromatophilic erythrocytes. Hemolytic diseases (Mycoplasma infection and IMHA) were diagnostically excluded, and the cat was treated through prednisolone administration, whole blood transfusion, and administration of vitamins (K2 and B12); however, the anemia progressively worsened. Cabot rings were observed until Day 22 and subsequently disappeared as the number of nucleated RBCs increased, and the erythrocyte lineage shifted to immature population. On Day 42, peripheral blood examination revealed further left shifting and appearance of many rubriblasts. The patient died at home on Day 43. Necropsy revealed neoplastic cells infiltrating the bone marrow and other organs, which were immunopositive to CD71 which is an erythroid lineage marker. In humans, Cabot rings have been observed in megaloblastic anemia, lead poisoning, myelodysplastic syndrome, and myelofibrosis; further, they are thought to be related to stressed bone marrow and dyserythropoiesis. This is the first case report of a cat with Cabot rings, which are suggestive of defects in erythroid lineage production. [ABSTRACT FROM AUTHOR]

Background: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin‐related protein (SMRP) and cancer antigen 125 (CA‐125) are established blood‐based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD). Methods: Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post‐operation, and (3) recurrence. Results: Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow‐up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA‐125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease‐free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA‐125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA‐125 across the study timepoints (p = 0.47). Conclusions: Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA‐125 could be helpful in recognizing abdominal recurrences. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess whether circulating histone‐specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE). Methods: Seroprevalence of autoantibodies and HLA‐DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA–peptide autoepitope couples for ex vivo detection of antigen‐specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA‐DRB1*03:01 and/or HLA‐DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission. Results: Histone‐specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti‐DNA antibodies, 77% had detectable histone‐specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone‐specific regulatory and effector T helper (Th) 1‐, Th2‐, and atypical Th1/Th17 (Th1*)‐polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1‐, Th2‐, and Th1*‐polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone‐specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone‐specific naive T (TN) and terminally differentiated T cells. Conclusion: Histone‐specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy. [ABSTRACT FROM AUTHOR]

There are two FDA‐approved bisphosphonate products, clodronate (Osphos®) and tiludronate (Tildren®), for use in horses. It is hypothesized that bisphosphonates can produce analgesic effects and prevent proper healing of microcracks in bone. Therefore, bisphosphonate use is banned in racehorses. However, bisphosphonates have a short detection window in the blood before sequestration in the skeleton, making the reliability of current drug tests questionable. Seven exercising Thoroughbred horses were administered clodronate (1.8 mg/kg i.m.), and four were administered saline. RNA was isolated from peripheral blood mononuclear cells (PBMCs) collected immediately before a single dose of clodronate or saline and then on Days 1, 6, 28, 56 and 182 post‐dose. mRNA was sequenced and analysed for differentially expressed transcripts. While no single transcripts were differentially expressed, pathway analysis revealed that p38 MAPK (p =.04) and Ras (p =.04) pathways were upregulated, and cadherin signalling (p =.02) was downregulated on Day 1. Previously investigated biomarkers, cathepsin K (CTSK) and type 5 acid phosphatase (ACP5), were analysed with RT‐qPCR in a targeted gene approach, with no significant difference observed. A significant effect of time on gene expression for ACP5 (p =.03) and CTSK (p <.0001) was observed. Thus, these genes warrant further investigation for detecting clodronate use over time. [ABSTRACT FROM AUTHOR]

Background: Today, with wars raging in Ukraine and the Middle East, the demand for blood is high. Despite this, few companies produce the necessary equipment to draw, store, and transfuse whole blood. This study evaluated the safety and performance of a 3D printed bottle cap in conjunction with a water bottle and some available consumables to draw and store fresh whole blood. Study Design and Methods: Bags of saline, and freshly donated whole blood, was transferred to the water bottle through a 3D printed bottle cap and stored for 72 h. An identical setup, transferring saline to a Terumo blood collection bag was used as control. Performance and safety were evaluated by calculating infusion rate and observing for backflow, respectively. The blood was also tested for hemolysis and bacterial growth at four sampling points. Results: The cap‐and‐bottle setup was faster than control in terms of flow rate when transferring saline (1.53 vs. 1.81 mL/s, p <.001), and non‐inferior to saline control when transfusing blood (1.53 vs. 1.49 mL/s, p =.641). We did not observe any risks of causing the donor iatrogenic harm, and there was no evidence of increased hemolysis. However, there were traces of bacterial contamination in three of six bottles. Conclusion: This study indicates that drawing blood is both feasible and safe, utilizing a 3D printed cap and bottle setup. Flow rate was faster than control, and mechanical properties of the blood were not affected. We were unable to determine the source of bacterial contamination in the blood. [ABSTRACT FROM AUTHOR]

Introduction: The use of low titer O whole blood (LTOWB) has expanded although it remains unclear how many civilian trauma centers are using LTOWB. Methods: We analyzed data on civilian LTOWB recipients in the American College of Surgeons Trauma Quality Improvement Program (TQIP) database 2020–2021. Unique facility keys were used to determine the number of centers that used LTOWB in that period. Results: A total of 16,603 patients received LTOWB in the TQIP database between 2020 and 2021; 6600 in 2020, and 10,003 in 2021. The total number of facilities that reported LTOWB use went from 287/779 (37%) in 2020 to 302/795 (38%) in 2021. Between 2020 and 2021, among all level 1–3 designated trauma facilities that report to TQIP LTOWB use increased at level‐1 centers (118 to 129), and level‐2 centers (81 to 86), but decreased in level‐3 facilities (9 to 4). Among pediatric and dual pediatric‐adult designated hospitals there was a decrease in the number of pediatric level‐1 centers (29 to 28) capable of administering LTOWB. Among centers with either single or dual level‐1 trauma center designation with adult centers, the number that administered LTOWB to injured pediatric patients also decreased from 17 to 10, respectively. Conclusions: There was an increase in the number of facilities transfusing LTOWB between 2020 and 2021. The use of LTOWB is underutilized in children at centers that have it available. These findings inform the expansion of LTOWB use in trauma. [ABSTRACT FROM AUTHOR]

Background: The Role 2 setting represents the most far‐forward military treatment facility with limited surgical and holding capabilities. There are limited data to guide recommendations on blood product utilization at the Role 2. We describe the consumption of blood products in this setting. Study Design and Methods: We analyzed data from 2007 to 2023 from the Department of Defense Trauma Registry (DODTR) that received care at a Role 2. We used descriptive and inferential statistics to characterize the volumes of blood products consumed in this setting. We also performed a secondary analysis of US military, Coalition, and US contractor personnel. Results: Within our initial cohort analysis of 15,581 encounters, 17% (2636) received at least one unit of PRBCs or whole blood, of which 11% received a submassive transfusion, 4% received a massive transfusion, and 1% received a supermassive transfusion. There were 6402 encounters that met inclusion for our secondary analysis. With this group, 5% received a submassive transfusion, 2% received a massive transfusion, and 1% received a supermassive transfusion. Conclusions: We described volumes of blood products consumed at the Role 2 during recent conflicts. The maximum number of units consumed among survivors exceeds currently recommended available blood supply. Our findings suggest that rapid resupply and cold‐stored chain demands may be higher than anticipated in future conflicts. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA‐based MRD detection to predict recurrence in a real‐world cohort of primarily early‐stage non‐small cell lung cancer (NSCLC) patients treated with curative intent. Methods: Longitudinal plasma samples were collected post curative‐intent treatment from 36 patients with stage I–IV NSCLC. A personalized, tumor‐informed assay was used to detect and quantify ctDNA in plasma samples. Results: Of the 24 patients with plasma samples available during the MRD window (within 6 months of curative surgery and before adjuvant therapy), ctDNA was detectable in two patients. Patients with ctDNA‐positivity during the MRD window were 15 times more likely to recur compared to ctDNA‐negative patients (HR: 15.0, 95% CI: 1.0–253.0, p = 0.010). At any time post‐curative intent treatment, ctDNA‐positivity was associated with significantly poorer recurrence‐free survival compared to persistently ctDNA‐negative patients (p < 0.0001). Conclusion: Our real‐world data indicate that longitudinal, personalized, tumor‐informed ctDNA monitoring is a valuable tool in patients with NSCLC receiving curative treatment to identify patients at high risk for recurrence. [ABSTRACT FROM AUTHOR]

This study investigated the concentrations of heavy metals in the water sources of the upstream region of the Huangpu River, the Yangtze River Estuary, and various areas in Shanghai, as well as the heavy metal concentrations in the blood of Shanghai residents. It aimed to analyze the heavy metal elements absorbed by the human body and the resulting pathological effects. The results revealed that surface water primarily contains five heavy metals: copper (Cu), lead (Pb), zinc (Zn), arsenic (As), and mercury (Hg), while water sediments primarily contain seven heavy metals: Cu, cadmium (Cd), Pb, chromium (Cr), Zn, As, and Hg. The main heavy metals present in the human body are Pb, Hg, As, and Cd. By reviewing previous articles, it was found that heavy metal concentrations in human blood are higher than those in surface water, suggesting uncertainties in the heavy metal content of surface water and its tendency to settle at the bottom. Furthermore, a comparison of heavy metal content in sediments revealed that Hg is the most readily absorbed heavy metal by the human body and is also a toxic environmental pollutant. Within the cell, Hg is highly toxic to mitochondria and may cause oxidative stress and neurodegenerative disease. This study concludes that water sediments serve as the major source of pollution in the human body and pose significant health risks, thereby necessitating the implementation of effective preventive measures. [ABSTRACT FROM AUTHOR]

As first‐line antimalarials used in the artemisinin combination therapy, artemisinin drugs exert their action inside red blood cells. However, the blood pharmacokinetic characteristics of artemisinin drugs have not been fully revealed owing to their built‐in chemical instability initiated by Fe2+ released from hemoglobin, with limited information on their metabolites. In this study, liquid chromatography tandem high‐resolution mass spectrometric (LC–HRMS) methods were developed for the quantification of two representative artemisinin drugs (artemisinin, ART; dihydroartemisinin, DHA) and their respective metabolite (deoxyartemisinin, D‐ART; dihydroartemisinin glucuronide, DHA‐Glu) in rat blood/plasma. The blood samples were pretreated with the stabilizer (0.4 m potassium dichromate and 3% EDTA‐2Na). The methods displayed excellent specificity, linearity, accuracy and precision for ART (17.7–709.2 nm) and its metabolite D‐ART (18.8–751.9 nm), and the linear range was 40.0–4,000.0 nm for both DHA and DHA‐Glu. The methods were successfully applied to the pharmacokinetic studies of ART and DHA in rats. The blood‐to‐plasma ratio was 0.8–1.5 for ART, 1.0–1.5 for D‐ART, 1.2–2.2 for DHA and 0.9–1.3 for DHA‐Glu, which was time dependent. The results indicated that artemisinin drugs and their metabolites showed a high but different blood‐to‐plasma ratio, which should be considered when optimizating their dosing regimens or evaluating their clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To define the utility of the Triage Revised Trauma Score (TRTS), GCS/Age/arterial Pressure (GAP) score, and shock index (SI) in predicting the need for in‐flight blood product administration in civilian trauma patients transported by an aeromedical platform.A retrospective chart review of 3582 aeromedical trauma cases was conducted. An initial TRTS, GAP score and SI were calculated for each patient, and the administration of in‐flight blood products was also recorded. Receiver operating characteristic (ROC) curves were used to quantify the predictive discrimination of the TRTS, GAP score and SI on the need for in‐flight blood product administration.The SI showed a superior predictive value compared to the TRTS and GAP score. The SI showed an area under the curve on the ROC curve of 0.85 in both primary and inter‐hospital transfer cases, indicating reasonable predictive value.The SI demonstrates favourable test characteristics for predicting the need for in‐flight blood product administration. Prospective validation of these results is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Myelomonocytic Leukemia (CMML) and Myelodysplastic Syndromes (MDS) are increasingly represented in the general population. We propose a screening strategy based on algorithms calculated from quantitative and analytical data from the XN analyser. Materials and Methods: We tested the performance of previously published MDS and CMML scores on an evaluation cohort of 749 individual eligible patients over 50 years of age. These patients were classified into 3 groups as follows: 713 patients without MDS or CMML, 18 patients with MDS, and finally 18 patients with CMML. In a second step, a routine cohort of 37 828 samples was studied to evaluate the impact of this approach. Results: The concordance rate between cytology and the two scores is 92.1%. The sensitivity and specificity of the CMML score are 100% and 96.2%, respectively. For the MDS score, they are 83.3% and 89.6% respectively. The ratio of platelets measured by fluorescence on board (PLT‐F) as reflex tests generated is 1.5% after 6 months. The additional smear ratio for suspected MDS is calculated at 0.6%. Conclusion: We propose a flowchart using embedded artificial intelligence to help the cytologist in an optimized smear review and thus improve guidance to the clinician and the patients in the diagnosis process. This strategy permits a more comprehensive approach to MDS and CMML detection fitting with the new definition of CMML according to the recommendations of the World Health Organization (WHO) published in 2022. [ABSTRACT FROM AUTHOR]

Objective: To benchmark blood culture (BC) quality in an Australian ED, explore groups at risk of suboptimal BC collection, and identify potential areas for improvement. Methods: This retrospective observational study was undertaken to benchmark quality of BCs in a tertiary adult ED in terms of number of BC sets per patient and proportion of patients with false positive (contaminated) BC results. Results: A single BC set was taken for 55% of patients, with lower acuity patients being more likely to have a single BC set taken. BC false positives occurred in 3.4% of presentations, with higher frequency in some critically unwell patient groups. The true positive BC rate was 10.9%, with pathogens most frequently isolated in older patients, those with a haematological condition or genitourinary source, and those admitted to inpatient wards. Hospital length of stay did not differ between patients with negative and patients with false positive BCs. Conclusions: BC quality standards in the ED such as false positive rate <3% and single culture rate <20% are required to facilitate benchmarking and prospective quality improvement. The sensitivity and specificity of this common and critical test can be improved. Patient subgroups associated with poor‐quality BC collection can be identified and should be a focus of future work. [ABSTRACT FROM AUTHOR]

Animal flesh foods are rich in bioavailable iron but infrequently consumed by young children. We aimed to determine whether flesh food intake was associated with iron and anaemia status among 585 Malawian infants enroled in a 6‐month egg‐feeding trial. The percentage of days of small fish, large fish and meat consumption were assessed through weekly 7‐day animal‐source food screeners. Grams of intake were assessed through 24‐h recalls conducted at 6–9, 9–12 and 12–15 months of age. Plasma ferritin, soluble transferrin receptor (sTfR) and haemoglobin concentrations were measured at 6–9 and 12–15 months of age. Iron biomarkers were adjusted for inflammation during analysis. At enrolment, each flesh food category was consumed by <5% of children in the past 24 h. Over the next 6 months, small fish, large fish and meat were consumed on 25%, 8% and 6% of days, respectively, with mean usual intakes of <5 g/day. More frequent small fish consumption was associated with lower sTfR (geometric mean ratio [95% CI]: 0.98 mg/L [0.96, 1.00] per 10 percentage point difference) but not ferritin (1.03 µg/L [0.98, 1.07]) or haemoglobin (1.01 g/dL [1.00, 1.01]). Large fish consumption was associated with higher anaemia (prevalence ratio [95% CI]: 1.09 [1.01, 1.19]) and lower iron deficiency (0.96 [0.93, 1.00]) prevalence. Gram intakes of flesh food categories were not associated with any iron or anaemia indicators. Small fish were a primary contributor to flesh food intake in this cohort of Malawian children, although usual portions were small. Fish was associated with modest improvements to iron status, but meat was too infrequent to be associated with anaemia and iron deficiency. Key messages: Small fish was the most frequently consumed flesh food among young children: 4% at enrolment and 40% at the 6‐month follow‐up. On average, children consumed small fish once every 4 days.Despite small usual portions of about 5 g/day, frequent consumption of small fish was associated with moderate improvements in iron status.Large fish consumption was associated with lower iron deficiency but not with mean plasma ferritin or sTfR. Meat was infrequently consumed and not associated with any iron or anaemia measures.Reducing the burden of iron deficiency among young Malawian children may require provision of supplemental dietary iron, improved complementary feeding practices, addressing underlying barriers to flesh food consumption and controlling inflammation and infectious diseases. [ABSTRACT FROM AUTHOR]

Background and Objectives: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion‐transmitted infections. This project reviewed NAT for screening blood donations globally. Materials and Methods: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion‐transmitted Infectious Diseases (ISBT WP‐TTID), was distributed through ISBT WP‐TTID members. Data were analysed using descriptive statistics. Results: Forty‐three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT‐positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT‐positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT‐positivity rate was higher in first‐time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). Conclusion: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT. [ABSTRACT FROM AUTHOR]

Studies on the bioaccumulation and toxicity of contaminants in Crocodylians are scarce. We evaluated alterations in concentrations of the nondestructive biomarkers butyrylcholinesterase (BChE), glutathione‐S‐transferase (GST), superoxide dismutase (SOD), and reduced glutathione (GSH), together with bioaccumulation of the metals iron (Fe), copper (Cu), zinc (Zn), manganese (Mn), chronium (Cr), aluminium (Al), and lead (Pb) in Caiman latirostris captured in Tapacurá Reservoir (TR; São Lourenço da Mata, Pernambuco, Brasil), in urbanized areas of Pernambuco State (UA; Brasil) and from the AME Brasil caiman farm (AF; Marechal Deodoro, Alagoas, Brasil); the latter was used as a potential reference with low levels of contamination. For metal analysis, 500 µL of blood was digested in 65% HNO3 and 30% H2O2. The samples were analyzed by inductively coupled plasma–optical emission spectrometry. For analysis of biomarkers, an aliquot of blood was centrifuged to obtain plasma in which biochemical assays were performed. Blood concentrations of metals analyzed in animals from AF were lower compared with TR and UA, confirming that animals from the caiman farm could be used as references with low levels of contamination. Iron, Cu, Mn, Al, and Pb exceeded toxic levels for other vertebrates in animals from TR and UA. Butyrylcholinesterase activity showed significant reduction in adults from UA and TR compared with AF. An increase in the activity of GST and GSH, in adults of TR and UA in relation to AF, was verified. Superoxide dismutase activity showed a significant reduction in adults of TR in relation to AF, and the concentrations of Cu and Mn were negatively correlated with SOD activity. Animals from UA and TR showed greater concentrations of the analyzed metals compared with reference animals, and changes in biomarkers were seen, confirming the potential of these nondestructive chemical and biological parameters in blood of C. latirostris for biomonitoring of pollution. Environ Toxicol Chem 2024;43:878–895. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) contain a plethora of biomolecules, including nucleic acids, with diverse diagnostic and therapeutic application potential. Although reverse transcription‐quantitative PCR (RT‐qPCR) is the most widely applied laboratory technique to evaluate gene expression, its applicability in EV research is challenged by the lack of universal and stably present reference genes (RGs). In this study, we identify, validate and establish SNRPG, OST4, TOMM7 and NOP10 as RGs for the normalization of EV‐associated genes by RT‐qPCR. We show the stable presence of SNRPG, OST4, TOMM7 and NOP10 in multiple cell lines and their secreted EVs (n = 12) under different (patho)physiological conditions as well as in human‐derived biofluids (n = 3). Enzymatic treatments confirm the presence of SNRPG, OST4, TOMM7 and NOP10 inside EVs. In addition, the four EV‐associated RGs are stably detected in a size‐range of EV subpopulations. RefFinder analysis reveals that SNRPG, OST4, TOMM7 and NOP10 are more stable compared to RGs established specifically for cultured cells or tissues such as HMBS, YWHAZ, SDHA and GAPDH. In summary, we present four universal and stably present EV‐associated RGs to enable normalization and thus steer the implementation of RT‐qPCR for the analysis of EV‐associated RNA cargo for research or clinical applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPSvenous) for the diagnosis and monitoring of neurodegenerative diseases in remote settings. METHODS: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (Aβ) 40, Aβ42; and phosphorylated tau (p‐tau181 and p‐tau217) were measured in paired DPSvenous and ethylenediaminetetraacetic acid plasma samples with single‐molecule array. In the validation cohort, a subset of participants (n = 99) had cerebrospinal fluid (CSF) biomarkers. RESULTS: All DPSvenous and plasma analytes correlated significantly, except for Aβ42. In the validation cohort, DPSvenous GFAP, NfL, p‐tau181, and p‐tau217 differed between CSF Aβ‐positive and ‐negative individuals and were associated with worsening cognition. DISCUSSION: Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPSvenous extends the utility of blood‐based biomarkers to remote settings with simplified sampling conditions, storage, and logistics. Highlights: A wide array of biomarkers related to Alzheimer's disease (AD) and neurodegeneration were detectable in dried plasma spots (DPSvenous).DPSvenous biomarkers correlated with standard procedures and cognitive status.DPSvenous biomarkers had a good diagnostic accuracy discriminating amyloid status.Our findings show the potential interchangeability of DPSvenous and plasma sampling.DPSvenous may facilitate remote and temperature‐independent sampling for AD biomarker measurement.Innovative tools for blood biomarker sampling may help recognizing the earliest changes of AD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Blood protein biomarkers demonstrate potential for Alzheimer's disease (AD) diagnosis. Limited studies examine the molecular changes in AD blood cells. METHODS: Bulk RNA‐sequencing of blood cells was performed on AD patients of Chinese descent (n = 214 and 26 in the discovery and validation cohorts, respectively) with normal controls (n = 208 and 38 in the discovery and validation cohorts, respectively). Weighted gene co‐expression network analysis (WGCNA) and deconvolution analysis identified AD‐associated gene modules and blood cell types. Regression and unsupervised clustering analysis identified AD‐associated genes, gene modules, cell types, and established AD classification models. RESULTS: WGCNA on differentially expressed genes revealed 15 gene modules, with 6 accurately classifying AD (areas under the receiver operating characteristics curve [auROCs] > 0.90). These modules stratified AD patients into subgroups with distinct disease states. Cell‐type deconvolution analysis identified specific blood cell types potentially associated with AD pathogenesis. DISCUSSION: This study highlights the potential of blood transcriptome for AD diagnosis, patient stratification, and mechanistic studies. Highlights: We comprehensively analyze the blood transcriptomes of a well‐characterized Alzheimer's disease cohort to identify genes, gene modules, pathways, and specific blood cells associated with the disease.Blood transcriptome analysis accurately classifies and stratifies patients with Alzheimer's disease, with some gene modules achieving classification accuracy comparable to that of the plasma ATN biomarkers.Immune‐associated pathways and immune cells, such as neutrophils, have potential roles in the pathogenesis and progression of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Despite prevention efforts, many cases of mushroom poisoning are reported around the world every year. Among the different toxins implicated in these poisonings, muscarine may induce parasympathetic neurological damage. Muscarine poisonings are poorly reported in the current literature, implying a lack of available data on muscarine concentrations in human matrices. A validated liquid chromatography with high‐resolution mass spectrometry detection (Orbitrap technology) method was developed to determine muscarine concentrations in human urine, plasma, and whole blood samples. Muscarine was determined using 100 μL of biological fluids, and precipitation was used for sample preparation. Liquid chromatography‐mass spectrometry was performed using an Accucore Phenyl‐X analytical column with the electrospray source in positive ion mode. Muscarine was quantitated in parallel reaction monitoring (PRM) mode with D9‐muscarine as the internal standard. The method was validated successfully over the concentration range 0.1–100 μg/L for plasma and whole blood and 1–100 μg/L for urine, with acceptable precision and accuracy (<13.5%), including the lower limit of quantification. Ten real cases of suspected muscarine poisoning were successfully confirmed with this validated method. Muscarine concentrations in these cases ranged from 0.12 to 14 μg/L in whole blood,

The article focuses on the impact of pre-hematopoietic cell transplantation (HCT) dental clearance on the incidence of bacteremia caused by bacteria predominantly found in the oral cavity. It examines whether dental clearance before HCT reduces the risk of bacteremia during the pre-engraftment phase and explores various factors related to dental health and their correlation with bacteremia outcomes.

A recent study published in The New England Journal of Medicine investigated the effectiveness of a new blood-based test called Shield for screening colon cancer. The test is meant for average-risk individuals with no family or personal history of colon cancer or advanced polyps. The study found that the Shield test was as effective as stool-based tests for detecting colon cancer, particularly early-stage cancers. However, it was less sensitive for detecting advanced precancerous lesions. The researchers believe that this blood test could improve screening rates and potentially reduce colon cancer deaths. [Extracted from the article]

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]

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]

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]

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]

The dynamics of blood conveying gold nanoparticles (GNPs) are helpful to the health workers while air conveying dust particles over rockets is helpful to space scientists during the testing phase. However, little is known on the significance of thermal diffusivity in these aforementioned cases. In this report, the partial differential equation suitable to unravel the implication of increasing partial slip and viscous dissipation on the dynamics of the mixture of (i) blood and nano size of GNPs (ii) air and dust particles on an object with an increasing diameter (uhspr) is investigated. The density, zero shear rate viscosity, heat capacity, and thermal conductivity treated in this study vary with volume fraction nanoparticles. In the second case, the interaction between the solid particles and air is incorporated into the momentum equation using the Stokes drag. Transformation and parametrization of the two‐dimensional nonlinear partial differential equations were obtained with the aid of suitable similarity variables. Thereafter, the numerical solutions of the corresponding boundary valued problems were obtained using the classical Runge–Kutta integration scheme together with shooting techniques and Matlab bvp5c package. Enhancement in the rate of viscous dissipation is a major factor suitable to increase the velocities of both fluids, boost temperature distribution across both fluids, and local skin friction coefficients. There exist a significant difference between the effect of partial slip on the dynamics of blood‐gold nanofluid and dusty fluid. [ABSTRACT FROM AUTHOR]