Blood Levels Research Articles

Maternal and Cord Blood Levels of Metals and Fetal Liver Function

Exposure to metals during pregnancy has been associated with adverse birth outcomes, but its impact on fetal liver function remains poorly understood. This study for the first time aimed to investigate the association between maternal and umbilical cord blood Metals levels and umbilical liver enzymes. A comprehensive analysis was conducted on 450 mother-newborn pairs in 2022, measuring 13 Metals in serum samples from pregnant women during the third trimester and umbilical cord blood samples. Regression analyses were utilized to examine the relationship between levels of maternal and umbilical cord blood Metals and the levels of gamma-glutamyl transferase (GGT), umbilical alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). G-comp analyses evaluated the combined effect of metals exposure on umbilical liver enzymes. Elevated levels of certain Metals in cord blood and maternal samples were positively linked with increased umbilical GGT, ALP, ALT, and AST levels. Notably, zinc (Zn) levels in cord blood exhibited an inverse correlation with umbilical liver enzyme levels. Furthermore, g-comp analyses revealed significant positive associations between exposure to metals mixtures and umbilical liver enzyme levels. An increase of one quartile in the mixture of maternal and umbilical Metals was linked with 99.45 U/L (95% CI:37.72, 161.19, p < 0.01), 2.79 (95% CI: 0.92, 4.65, p < 0.01), and 87.17 (95% CI: 53.96, 120.38, p < 0.01) increase in ALP, ALT and GGT levels. Further examination of the weight of Metals revealed As, Cd, Ni, Pb, Hg and Cr with the highest positive effects and Zn with the highest negative effect in the mixture effect on the umbilical liver enzyme. In summary, our results underscore the potential influence of prenatal heavy metal exposure on fetal liver function.

The Association of Nasal and Blood Eosinophils with Serum IgE Level in Allergic Rhinitis and Asthma: A Case-Control Study.

Allergic rhinitis and asthma are two common respiratory diseases with allergic etiology in the world's population. Eosinophils and serum IgE levels have been known as inflammatory allergy markers for many years. This study aimed to evaluate the correlation of nasal and blood eosinophils with serum IgE levels in allergic rhinitis and asthma patients. This prospective study was done on patients (n = 78) diagnosed with asthma (n = 20), allergic rhinitis (n = 49), and chronic rhinosinusitis with nasal polyposis (CRSwNP) (n = 9) at our hospital in Ahvaz City, Iran. The age of participants in our study ranged from 3 to 73 years, and all of them were subjected to a complete blood count (CBC) test, nasal smear, and determination of serum IgE levels after their consent. There was no correlation between serum IgE level and nasal eosinophil count (p = 0.728) or between serum IgE level and blood eosinophil count (p = 0.657); however, a positive correlation was detected between blood and nasal eosinophil levels (p = 0.003). There is no significant relationship between serum IgE level and eosinophil count in the blood and nasal secretions. Serum IgE level and blood or nasal eosinophil count are both useful biomarkers for monitoring allergic rhinitis and asthma individually, but no diagnostic conclusion can be drawn from their correlation.

Interactions between blood lead (Pb) concentration, oxidative stress, cellular immune response and reproductive status in livestock from a mining area

Chronic exposure to lead (Pb) in livestock grazing in abandoned mining areas affects animal welfare and productivity, as well as represents a significant food safety risk. Here, we evaluate the physiological effects of Pb exposure in goats maintained under extensive farming conditions in a non-remediated mining area. We monitored blood, fecal, and milk Pb levels in two groups of goats, pregnant (n=17) and lactating (n=24), kept in different enclosures with high soil Pb concentrations (geometric means of 270 and 143 μg/g, respectively) in Sierra Madrona mining district (Spain). We also studied the influence of Pb exposure on the ability to mount a cellular immune response, and on oxidative stress and biochemical biomarkers measured in blood. Blood Pb concentration was higher in pregnant than in lactating goats, but this difference was not observed in fecal Pb concentration. Pb levels in feces and milk concentrations were correlated with those measured in blood, with 11% of milk samples showing Pb concentrations above the maximum level (ML) for Pb in raw milk established by the EU (0.02 μg/g wet weight). Animals with increased blood Pb levels showed reduced concentrations of retinol in plasma, but these Pb levels did not affect the cellular immune response. The stimulation of the cellular immune response in lactating goats was associated with an increase in blood Pb and calcium (Ca) levels. The reproductive status and age of goats significantly affected several oxidative stress, antioxidants and plasma biochemistry variables. Goats grazing on soils contaminated by past Pb mining activities may be susceptible to detrimental health effects mediated by retinol deficiency. In view of the detected transfer of Pb through milk, special attention should be paid to the food safety of derived products (i.e. cheese).

Interferon-gamma driven elevation of CXCL9: a new sepsis endotype independently associated with mortality

Endotype classification becomes the cornerstone of understanding sepsis pathogenesis. Macrophage activation-like syndrome (MALS) and immunoparalysis are the best recognized major endotypes, so far. Interferon-gamma (IFNγ) action on tissue macrophages stimulates the release of the cytotoxic chemokine CXCL9. It was investigated if this mechanism may be an independent sepsis endotype. In this cohort study, 14 patient cohorts from Greece, Germany and Italy were studied. The cohorts were 2:1 randomly split into discovery and validation sets. Sepsis was defined by the Sepsis-3 definitions and blood was sampled the first 24h from meeting the Sepsis-3 definitions. Concentrations of IFNγ, CXCL9, IP-10 (IFNγ induced protein-10), soluble CD163 and ferritin were measured. The endotype of IFNγ-driven sepsis (IDS) was defined in the discovery set as the combination of a) blood IFNγ above a specified cut-off associated with the minimal risk for immunoparalysis (defined as ≥8000 HLA-DR receptors on CD45/CD14-monoytes); and b) increase of CXCL9. Results were compared to the validation set. 5503 patients were studied; 3670 in the discovery set and 1833 in the validation set. IDS was defined as IFNγ more than 3pg/ml and CXCL9 more than 2200pg/ml. The frequency of IDS in the discovery set was 19.9% (732 patients; 95% confidence intervals-CIs 18.7-21.3%) and in the validation set 20.0% (366 patients; 95% CIs 18.2-21.9%). Soluble CD163, a marker of macrophage activation, was greater in IDS and IDS had features distinct from MALS. The mortality in IDS patients was 43.0% (315 patients; 95% CIs 39.5-46.6%) in the discovery set and 40.4% in the validation set (148 patients; 95% CIs 35.5-45.5%) (p=0.44 compared to patients of the discovery set). IDS was an independent risk factor for death in the presence of other endotypes, severity scores and organ dysfunctions of the multivariate model [hazard ratio 1.71 (95% CIs 1.45-2.01) in the discovery set and 1.70 (95% CIs 1.34-2.16) in the validation set]. Decreases of IFNγ and CXCL9 blood levels within the first 72h were associated with better outcome. IDS is a new sepsis endotype independently associated with unfavorable outcome. Hellenic Institute for the Study of Sepsis; Horizon 2020 project ImmunoSep; Swedish Orphan BioVitrum AB (publ) and German Federal Ministry of Education and Research.

Cyclosporine's immunosuppressive effects, entwined toxicity, and clinical modulations of an organ transplant drug.

The discovery and use of cyclosporine since its inception into the clinics in the '70s and up have played a crucial role in the advancement of transplant therapy and containment of immune-based rejections. The drug had improved rates of acute rejections, and supported early graft survival. However, the long-term survival of renal allografts is still less prevalent, and an in-depth analysis and reported findings led us to believe that there is a chronic irreversible component to the drug that is tackled through its metabolites, and causes toxicity, which led to new therapies, including monoclonal antibody based medications. A recap of the immunosuppressive effects and entwined toxicity of the drug, now relegated to solid transplants, overviews the past protocols used to minimize and avoid, or use in combination with this calcineurin inhibitor class drug with other drugs. The current review circumvents the cyclosporine's mechanism of action, pathophysiology, cytochrome roles, and other factors associated with acute and chronic toxicity. It also attempts to find conclusive strategies reported in recent studies to avoid its toxic side effects and develop a safe-use strategy for the drug. Gastrointestinal decontamination, supporting the airway, monitoring for signs of respiratory insufficiency, monitoring for severe reactions such as seizures, administration of oxygen, and avoiding the administration of drugs that increase the blood levels of cyclosporine are beneficial interventions when encountering cyclosporine toxicity cases. The constrained therapeutic outcome has also led to redesign, and combine formulation to review the pharmacokinetics of the drug.

Primary hyperparathyroidism with intrathyroidal location of parathyroid adenoma

Primary hyperparathyroidism is a common endocrine disease with high morbidity and mortality from all causes. The disease can be asymptomatic and for a long time remain undiagnosed, which leads to untimely surgical treatment, increases the risks of development and progression of severe disabling complications and worsens patients prognosis. In clinical practice there are certain difficulties in diagnosing this pathology. One of the urgent problems is the search for the source of parathyroid hormone hyperproduction, especially in case of atypical location of paraаdenoma. The most common atypical locations of altered parathyroid glands are thymus, retroor paraesophageal space, retropharyngeal space, mediastinum and thyroid gland. The frequency of intrathyroidal masses of parathyroid glands, in the thyroid parenchyma or under its capsule, ranges on average from 2 to 3%, but according to some authors can reach 18–22%. With such localization of paraadenomas there is a need for their differential diagnosis, first of all, with nodular formations of the thyroid gland. In addition, the absence of additional laboratory studies parathormone and calcium blood levels does not allow timely suspicion of the disease, and cytologic examination of the material obtained by fine-needle aspiration puncture biopsy does not allow reliable differentiation of the altered parathyroid gland. This article presents a clinical case of a patient with primary hyperparathyroidism with intrathyroidally located parathyroid adenoma, for a long time long identified as a “nodular goiter,” and provides a brief review of the methods that identify an intrathyroidally located parathyroma. Despite the abundance of diagnostic methods in visualization of intrathyroidal parathyroid glands, today the most appropriate seems to be expert ultrasound examination with assessment of the parathyroid hormone level in a washout after fine-needle aspiration, supplemented, if necessary, by scintigraphy and single-photon emission computed tomography combined with computed tomography or multispiral computed tomography.

Associations of mixed metals exposure with cognitive impairment risk: a cross-sectional study in Chinese adults.

Associations between exposure to single metals and cognitive impairment or related outcomes have been reported in many previous studies. However, co-exposure to more than one metal is common situation. In recent years, studies on the effects of exposure to multiple metals on cognitive impairment or related outcomes have increased, but remain very limited, with a focus on populations with occupational exposure to metals, children, and adolescents. The potential relationships between exposure to metal mixtures and risk of cognitive impairment in adults remain to be clarified. To determine the associations between blood metal mixtures and cognitive impairment risk. Inductively coupled plasma mass spectrometry (ICP-MS) was utilized to detect the blood levels of lead (Pb), iron (Fe), copper (Cu), calcium (Ca), magnesium (Mg), and zinc (Zn). Multivariable logistic regression and Bayesian kernel machine regression (BKMR) models were employed to assess the relationships of exposure to these blood metal mixtures with the risk of cognitive impairment. It was found that four metals (Pb, Fe, Cu, and Mg) were positively correlated with cognitive impairment in each single metal model. The association of Pb and Cu remained significant after adjusting for these six metals, with the odds ratios (95% confidence intervals) in the highest quartiles of 9.51 (4.41-20.54, p-trend <0.01) and 4.87 (2.17-10.95, p-trend <0.01), respectively. The BKMR models indicated that co-exposure levels of Ca, Cu, Fe, Mg, Pb, and Zn were related to increased risk of cognitive impairment at ≥25th percentile compared with median, and Pb and Cu mainly contributed to the joint effect. In addition, the interaction effects of Mg and Pb/Pb and Cu on the risk of cognitive impairment were observed. Co-exposure of six metals (Pb, Fe, Cu, Ca, Mg, and Zn) increased the risk of cognitive impairment in Chinese adults, with Pb and Cu likely to have greater impact. Potential interaction effects of Mg and Pb, Pb and Cu on the risk of cognitive impairment may exist.

Studies of Lipid Profiles Among Infants with Respiratory Distress Syndrome

Background: Respiratory distress syndrome (RDS) is known as hyaline membrane disease (HMD). It is the major cause of neonatal respiratory distress, especially in preterm infants Infants with RDS present with tachapnea, cyanosis, grunting, subcostal and intercostal retractions and nasal flaring. Oliguria with mild generalized edema may be present. Oxygen requirement may increase rapidly and is typically higher than that seen in infant with transient tachapnea of the newborn (TTN). Objective: to evaluate the relationship between the maternal and cord blood lipid profiles in preterm babies with respiratory distress syndrome. Methods: This is a case control study which was conducted on 50 preterm neonates admitted to the neonatal intensive care unit of Shebin El-Kom teaching hospital between January 2020 and October 2021. Results: the mean of total cholesterol was significantly higher in infants whose mothers had received antenatal steroid for lung maturity than those whose mothers had not (P&lt;0.05). But there was no significant difference in the mean of levels of TG, HDL-cholesterol, LDL-cholesterol and VLDL cholesterol between both groups. Also, There is a positive correlation between weight gain during pregnancy and neonatal cord blood levels of (Total cholesterol, TG, HDL-C, LDL-C and VLDL-C), There is a positive correlation between maternal blood levels of (total cholesterol, TG, LDL-C and VLDL-C) and their neonatal cord blood levels of (total cholesterol, TG, HDL-C, LDL-C and VLDL-C), There is a positive correlation between the maternal blood level of HDL-C and their neonatal cord blood levels of (total cholesterol and HDL-C).also, the cutoff values of cord blood (total Cholesterol, HDL-C, and LDL-C) below which RDS can be predicted are 80, 45.5 and 23.2 mg/dl respectively with a sensitivity of 83.3%, 86.7% and86.7% and with specificity of 95%, 80% and 70% respectively. Conclusion: RDS is accompanied with lipid alteration in the infants and their mothers. The results of this study point to the importance of measuring maternal serum and cord blood lipid profile as a predictor for the occurrence of RDS.

Depression in childhood to early adulthood and respiratory health in early adulthood.

Both depression and respiratory disease are common today in young populations. However, little is known about the relationship between them. This study aims to explore the association between depression in childhood to early adulthood and respiratory health outcomes in early adulthood, and the potential underlying mechanisms. A prospective study was conducted based on the Swedish BAMSE (Barn, Allergi, Miljö, Stockholm, Epidemiologi [Children, Allergy, Milieu, Stockholm, Epidemiology]) birth cohort (n = 4089). We identified clinically diagnosed depression through the dispensation of antidepressants, using national register data confirmed by self-reported diagnosis. At the 24-year follow-up, respiratory health was assessed via questionnaires and clinical evaluation. Metabolic and inflammatory profiles were analysed to explore potential mechanisms. Among the 2994 participants who provided study data, 403 (13.5%) had depression at any time point from around age 10 to 25 years. Depression was associated with higher risks of any chronic bronchitis symptoms (odds ratio = 1.58, 95% CI 1.21-2.06) and respiratory symptoms (odds ratio = 1.41, 95% CI 1.11-1.80) in early adulthood, independent of body mass index (BMI) and smoking status. Compared to individuals without depression, those with depression had a higher fat mass index (FMI (β = 0.48, 95% CI 0.22-0.74)) and increased blood levels of fibroblast growth factor 21 and Interleukin-6 in early adulthood. These markers together with FMI were found to partly mediate the association between depression and respiratory symptoms (total mediation proportion: 19.8 and 15.4%, respectively, P < 0.01). Depression in childhood to early adulthood was associated with an increased risk of respiratory ill-health in early adulthood, independently of smoking. Metabolic and inflammatory dysregulations may underlie this link.

Early high-dose cryoprecipitate to reduce mortality in adult patients with traumatic haemorrhage: the CRYOSTAT-2 RCT with cost-effectiveness analysis.

Traumatic haemorrhage is common after severe injury, leading to disability and death. Cryoprecipitate, a source of fibrinogen, may improve outcomes for patients with traumatic haemorrhage. To investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units, approximately 6g of fibrinogen) of cryoprecipitate on 28-day mortality. A randomised, parallel-group, unblinded, multicentre, international trial and economic evaluation. Patients were randomised to either the intervention (early cryoprecipitate) or the comparator (standard major haemorrhage protocol) arm via opaque, sealed envelopes in the emergency department or the transfusion laboratory/blood bank. All analyses were performed on an intention-to-treat basis. A cost-effectiveness analysis was undertaken. Twenty-five major trauma centres in the UK and one level 1 trauma centre in the USA. Adults who had traumatic haemorrhage following severe injury requiring activation of the major haemorrhage protocol and had received a blood transfusion. Early cryoprecipitate - 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g of fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of arrival at hospital in addition to standard major haemorrhage protocol or standard major haemorrhage protocol only. The primary outcome was all-cause mortality at 28 days. The secondary outcomes were all-cause mortality at 6 hours, 24 hours, 6 months and 12 months from admission; death from bleeding at 6 hours and 24 hours; transfusion requirements at 24 hours from admission; destination of participant at discharge; quality-of-life measurements (EuroQol-5 Dimensions, five-level version and Glasgow Outcome Scale) at discharge/day 28 and 6 months after injury; and hospital resource use up to discharge or day 28 (including ventilator-days, hours spent in critical care and inpatient stays). Eight hundred and five patients were randomised to receive the standard major haemorrhage protocol (control arm). Seven hundred and ninety-nine patients were randomised to receive an additional three pools of cryoprecipitate in addition to standard care (intervention arm). Baseline characteristics appeared well matched. Patients had a median age of 39 (interquartile range 26-55) years, and the majority (79%) were male. All-cause 28-day mortality (n=1531 patients; intention to treat) was 25.3% in the intervention arm compared with 26.1% in the control arm (odds ratio 0.96; p=0.74). There was variability in the timing of cryoprecipitate administration, with overlap between the treatment arms, limiting the degree of intervention separation. There was no evidence that early empiric administration of high-dose cryoprecipitate reduced the risk of death in unselected patients with traumatic haemorrhage. There was also no difference in adverse events. The cost-effectiveness of the intervention was similar to that of standard care. Research to evaluate if fibrinogen replacement is more beneficial for selected patients, for example those with low fibrinogen blood levels, is needed, as is further exploration of whether there is a difference in outcome according to mechanism of injury. This trial is registered as ISRCTN14998314. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/57/02) and is published in full in Health Technology Assessment; Vol. 28, No. 76. See the NIHR Funding and Awards website for further award information.

Effect of stimbiotic on growth performance, nutrient digestibility, oocyst shedding, blood profiles, and intestinal microbiota in necrotic enteritis-challenged broiler

This experiment was conducted to investigate the effect of stimbiotic (STB) in broilers with necrotic enteritis (NE). A total of 180 one-day-old Arbor Acres (initial body weight of 34.81 ± 1.04 g) were used in this experiment for 32 days. All broilers were randomly allocated into six treatments, and each experimental group had 10 replicate cages with three broilers per cage. The experiment was conducted in a 2 × 3 factorial design consisting of two levels of challenge (challenge and non-challenge) and three levels of STB (0, 0.05, and 0.1%). The NE challenge significantly decreased (P < 0.05) growth performance, heterophil levels in blood, and intestinal lesion scores compared to the non-challenge group. Supplementation of 0.05% STB significantly decreased (P < 0.05) feed conversion ratio and the number of oocysts per gram of feces compared to the supplementation of 0 and 0.1% STB. At the genus level, the supplementation of 0.05% STB significantly decreased (P < 0.05) the abundance of Enterobacterales compared to the other groups on d 32. In conclusion, supplementation with 0.05% STB in a diet could positively regulate the fecal microflora and alleviate the decline in growth performance and nutrient digestibility caused by NE.

Interleukin-6, C-Reactive Protein, and Recurrence After Stroke: A Time-Course Analysis of Individual-Participant Data.

Inflammation promotes atherogenesis. Randomized controlled trials of anti-inflammatory therapies for prevention after stroke have not yet demonstrated clear benefit. IL-6 (interleukin-6) and hsCRP (high-sensitivity C-reactive protein) are independently associated with major adverse cardiovascular events poststroke and may guide patient selection in future randomized controlled trials. Optimal timing of hsCRP/IL-6 measurement poststroke is unknown, as early blood levels may be confounded by the inflammatory response to brain infarction. Using individual-participant data from a systematic review, we performed a time-course analysis to investigate the association between hsCRP/IL-6 and recurrent events stratified by timing of sampling. The prespecified coprimary end points after sample measurement were: (1) recurrent major adverse cardiovascular events (first major coronary event, recurrent stroke, or vascular death) and (2) recurrent stroke (ischemic, hemorrhagic, or unspecified). The poststroke dynamics of IL-6/hsCRP were analyzed by plotting their median (interquartile interval) concentrations within each tenth of the sampling timeframe. Acute/postacute phases were defined for each biomarker according to the shape of this relationship. There were data for 9798 patients from 11 studies (19 891 person-years follow-up, 10 observational cohorts, and 1 randomized trial). Each marker was measured once. IL-6 was markedly elevated <24 hours poststroke compared with postacute levels (≥24 hours; 11.6 versus 3.02 pg/mL; P<0.001). HsCRP was elevated for 10 days. IL-6 was associated with recurrent major adverse cardiovascular events in the postacute phase (≥24 hours; risk ratio, 1.30 [CI, 1.19-1.41], per unit logeIL-6), but not in the acute phase (<24 hours; risk ratio, 1.10 [CI, 0.98-1.25]; Pinteraction=0.03). After adjustment for risk factors/medication, the association remained for postacute IL-6 when analyzed per logeunit (risk ratio, 1.16 [CI, 1.05-1.66]) and per quarter increase (risk ratio, 1.55 [CI, 1.19-2.02]; Q4 versus Q1), but not if measured acutely. Similar findings were observed for recurrent stroke. There was no evidence of time-dependent interaction with hsCRP. Timing of sample measurement after stroke modifies the association with recurrent major adverse cardiovascular events for IL-6 but not hsCRP. These data inform future randomized controlled trial designs incorporating biomarker-based selection of patients for anti-inflammatory therapies.

Gut Microbiota Composition Positively Correlates with Sports Performance in Competitive Non-Professional Female and Male Runners

There is still a pressing need for further investigation to bridge the gap in understanding the differences in gut microbiota composition between female runners and their male counterparts. We aimed to determine the gut microbiota composition in competitive non-professional female and male runners and to correlate the gut bacteria to performance. Our study included 40 subjects, of which 22 were runners (13 males and 9 females) and 18 control subjects (9 males and 9 females, representing the general population who perform light physical activity with a weekly running volume of ≤5 km per week). Fecal specimens were collected and analyzed for taxonomic profiling to compare species’ relative abundances between males and females based on the results of 16SrRNA analysis. Bacterial alpha and beta diversity were assessed to determine the differences in microbial composition between runners and controls, and between sexes. Each participant underwent a maximal oxygen consumption test and a time-to-exhaustion test at 85% of the measured VO2max. Blood lactate was collected every 5 min during the tests. Bacterial alpha diversity showed a significant difference (p = 0.04) between runners and controls. Taxonomic analysis of gut microbiota composition showed a lower Enterobacteriaceae abundance and a higher Methanosphaera abundance in runners compared with the control group. Ten different bacteria (Methanosphaera, Mitsuokella, Prevotellaceae, Megamonas, Rothia, Oscillospira, Bacteroides, Odoribacter, Blautia massiliensis, Butyricicoccus_pullicaecorum) were positively correlated with exercise (VO2max, lactate blood levels, time to exhaustion, and weekly training volume). We found no significant differences in the gut microbiota composition between male and female runners. Gut microbiota composition positively correlates with sports performance in competitive non-professional female and male runners, and female runners show similar gut microbiome diversity to male runners.

The participation of monoamines in the realization of vasopressin analgesic effects during electrical stimulation of paws in rats

BACKGROUND: Arginine vasopressin has been implicated in the modulation of stress and pain. The influence of a synthetic analogue of arginine vasopressin, 1-deamino-8-D-arginine-vasopressin, оn pain sensitivity, stress reactivity, levels of monoamines and brain neurotrophic factor in a model of paw electrical stimulation in rats has not been studied. AIM: The aim was to evaluate the effect of a synthetic vasopressin analog, 1-deamino-8-D-arginine-vasopressin, on pain sensitivity and the content of norepinephrine, serotonin, dopamine, brain neurotrophic factor in the parietal cortex and spinal cord in electrocutaneous paw stimulation test in rats. MATERIALS AND METHODS: The study was conducted on male Wistar rats who were injected with 1-deamino-8-D-arginine-vasopressin intranasally once a day for 5 days in small (single 20 ng, course 100 ng) and large doses (single 2 ug, course 10 ug). The content of brain neurotrophic factor in the parietal cortex and spinal cord, and corticosterone in blood serum were determined using enzyme immunoassay. The levels of norepinephrine, serotonin, dopamine and their metabolites in the brain were evaluated using high-performance liquid chromatography. RESULTS: 1-Deamino-8-D-arginine-vasopressin in different doses reduced pain sensitivity in rats, more pronounced when administered in large doses. The peptide in small doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid, a metabolite of serotonin; in the spinal cord, it reduced the content of 5-hydroxyindolacetic acid. 1-Deamino-8-D-arginine-vasopressin in high doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid; in the spinal cord ― reduced the content of serotonin and 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine; increased the levels of norepinephrine and homovanilic acid, a metabolite of dopamine. The peptide had no effect on corticosterone levels in the blood and brain neurotrophic factor levels in the brain in rats. CONCLUSIONS: The analgesic effects of 1-deamino-8-D-arginine-vasopressin were revealed with intranasal administration in different subendocrine doses. Regardless of the administered doses, dopamine and serotonin at the supraspinal level were involved in peptide-induced anesthesia; serotonin at the spinal cord level. More pronounced analgesia with the administration of 1-deamino-8-D-arginine-vasopressin in high doses was due to the additional involvement of dopamine and norepinephrine at the spinal cord level.

Dietary creatine and carcinogenic biomarkers in adult population.

Background: Several reports suggest potential cytotoxic effects of creatine, possibly due to its role in facilitating the formation of food-borne chemical carcinogenic compounds. Aim: This cross-sectional study aims to investigate the relationship between creatine consumption and various carcinogenic biomarkers in blood and urine among individuals aged 18 years and older, utilizing data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Methods: Daily creatine intake was assessed using the Dietary Data databases, which were compiled from individual in-person 24-h food recall interviews. The concentrations of carcinogenic compounds (heterocyclic amines, acrylamide, and formaldehyde) were extracted from NHANES 2013-2014 Laboratory Data database. Results: The final analysis included 1763 adult respondents, of whom 907 (51.4%) were female. The mean daily creatine intake was 0.83 ± 0.77 grams (95% CI, from 0.80 to 0.87). Regression analysis revealed no significant relationship between daily creatine intake and most carcinogenic biomarkers, except for a significant correlation (Model 1) between creatine intake and acrylamide levels (B = -3.999, ß = -0.088, p = 0.05). Model 2 (demographics) confirmed a significant relationship between daily creatine intake and circulating acrylamide (B = -3.490, ß = -0.077, p = 0.02), as well as for blood levels of glycidamide (B = -2.992, ß = -0.068, p = 0.05) and urinary 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (B = 0.190, ß = 0.088, p = 0.03). However, no correlation between creatine consumption and any carcinogenic biomarkers remained significant after adjusting for nutritional factors (Model 3) (p > 0.05). Conclusion: In conclusion, the consumption of dietary creatine may be considered safe and not associated with increased levels of above carcinogens in the general population.

Trace element contamination in three shorebird species migrating through Delaware Bay, New Jersey: arsenic, mercury and selenium are increasing.

Many shorebird populations are declining, and contaminants may be partly contributing to the decline by interfering with feeding, migration, and breeding success. The goal of our study was to determine whether there was a temporal change in concentrations of trace elements of red knot (Calidris canutus rufa), sanderling (Calidris alba), and ruddy turnstone (Arenaria interpres) during spring migration in Delaware Bay, New Jersey, USA. We sampled blood to 1) determine levels of trace elements in 2019, 2) compare 2019 trace element levels with those from shorebirds in 2011-2012, and 3) examine variability in blood levels of trace elements among species. In 2019: 1) trace element levels were significantly different among species (except cadmium[Cd]), 2) Cd was lowest in all species, and arsenic (As) and selenium (Se) were highest, and 3) sanderlings had the highest levels of As and Se, and knots had the highest levels of chromium (Cr) and lead (Pb). Se was higher in these shorebirds than reported for other shorebirds from elsewhere. As, mercury (Hg), and Se increased significantly between 2011-2012 and 2019 in all three species. There were no significant temporal changes in Cd. Chromium (Cr) decreased in knots and sanderling. The temporal increases in As, Se, and Hg bear watching as they are toxic in vertebrates, and each can decrease the toxicity of the others. The data indicate that shorebirds can be bioindicators of changing trace element levels in estuaries, potentially providing early warning of increasing levels of As, Hg, and Se in the environment.

An ensemble machine learning framework with explainable artificial intelligence for predicting haemoglobin anaemia considering haematological markers

Anaemia is a disorder marked by low blood levels of haemoglobin (HGB), affecting people of all ages and ethnicities and is a major global public health concern. Anaemia must be diagnosed as soon as possible to enable prompt treatment and intervention, which can reduce complications and enhance patient outcomes. With the ability to improve diagnostic precision and expedite patient care procedures, machine learning (ML) has become a potent instrument in the healthcare industry. Hence, we examine the use of ML approaches to predict haemoglobin-like anaemia in this research article. Based on a heterogeneous dataset of blood markars, we investigate the performance of many machine learning techniques such as Logistic Regression, CatBoost, XgBoost Decision Trees, KNN and others. The algorithms are further ensembled using a customized stacking approach. The ML models' judgments are interpreted using explainable artificial intelligence (XAI) methods. The xgboost and the stacking classifier obtained an accuracy, precision and recall of 99% each. Our research shows how ML models can help with the early diagnosis and treatment of anaemia, which will ultimately lead to better patient outcomes and healthcare results. Overall, the research shows how ML emphasizes the value of interdisciplinary cooperation in solving challenging medical problems.

Comparison of cord blood alarin levels of full-term infants according to birth weight.

To compare the cord blood alarin levels of infants in different birth weight groups with those of infantsborn to mothers diagnosed with gestational diabetes mellitus (GDM) who were not subgrouped according to birth weight. This prospective study was conducted between September 2023 and January 2024. Healthy term babies whose families agreed to participate in the study were divided into four groups according to their birth weight (small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA)) and whether their mothers had GDM. There was a significant difference between the cord blood alarin levels of the AGA and SGA groups (p=0.014). There was also a significant difference between the cord blood alarin levels of the AGA and GDM groups (p=0.012). However, the cord blood alarin levels of the LGA group (whose mothers did not have GDM) were similar to those of the AGA group (p=0.394). We found evidence that alarin levels in umbilical cord blood are associated with low birth weight and GDM.

Neutrophil extracellular traps, deoxyribonuclease and fibrosis in thoracic aortic aneurysm

Abstract Introduction Thoracic aortic aneurysm (TAA) is a rare but severe cardiovascular disease. The condition often goes undiagnosed, increasing the risk of acute aortic events. It is characterized by medial degeneration, caused by neutrophils infiltrating aortic tissue. Neutrophils can form proinflammatory and prothrombotic neutrophil extracellular traps (NETs), promoting disease progression. Purpose Recently, NETs and abdominal aortic aneurysm (AAA) were linked, while their effects on TAA development and progression remain unclear. We aimed to characterize NETs and NET-specific markers in tissue and plasma samples of TAA patients. Methods We included 171 patients with either ascending TAA (n=153) or Type A dissection (n=18). Healthy subjects were recruited as controls (n=135). Sample fiber composition was analyzed using trichrome; NET burden was quantified using immunofluorescence. Plasma NET surrogate markers including double-stranded (ds)DNA, myeloperoxidase (MPO), DNase activity and matrixmetalloproteinases (MMP) were measured using a fluorescence-based assay and ELISA, respectively. mRNA expression was assessed using qPCR. Results Median patient age was 65 years, and most were male (68.4%). Cardiovascular risk factors were common, including hypertension (77.8%), hyperlipidemia (57.9%), coronary artery disease (26.3%), and diabetes (18.7%). TAA patients were older with high BMI and impaired kidney function. Trichrome staining revealed abundant fibrotic material (median 47.99%), while collagen and elastic fiber distributions were 27.67% and 20.17%, respectively. TAA patients had increased amounts of aortic fibrotic material (47.99% vs 38.94%, p=0.001). Using immunofluorescence, we found higher NET expression in diseased tissue (0.87 [0.3, 1.85] vs 0.15 [0.03, 0.22]%, p=0.0017). This increase was primarily driven by the dissection patients (1.76 [0.89, 2.83]%, p=0.0037). Plasma MPO levels were increased in TAA compared to controls (36.93 [23.46, 57.55] vs 26.8 [19.7, 36.2]ng/mL, p&amp;lt;0.001), while DNase activity was decreased in patients (4.16 [2.66, 6.24] vs 6.06 [4.25, 8.11]mU/mL, p&amp;lt;0.001). Moreover, circulating plasma levels of MMP2 were elevated in TAA (250.36 [190.24, 351.32] vs 218.85 [171.32, 263.87]ng/mL, p=0.004). qPCR analysis of mRNA expressions in TAA cryospecimens revealed upregulations of TNFα (p=0.033) and CD45 (p=0.003), when compared to aortic disease-free controls. Conclusion Aortic fibrosis at the aneurysm site may be caused by inflammatory mechanisms involving TNFα and leucocytes (CD45+). High local NET-burden is indicative of activated neutrophils in the aortic media. TAA patients have suppressed DNase activity and higher MPO levels in venous blood, leading to dsDNA accumulation and increased neutrophil turnover. Elevated MMP2 suggests its involvement in TAA formation. Our findings could enable further research targeting NETs and inflammation in TAA, possibly finding novel therapies capable of mitigating aneurysm development.

Molecular landscape of the overlap between Alzheimer’s disease and somatic insulin-related diseases

Alzheimer’s disease (AD) is a multifactorial disease with both genetic and environmental factors contributing to its etiology. Previous evidence has implicated disturbed insulin signaling as a key mechanism that plays a role in both neurodegenerative diseases such as AD and comorbid somatic diseases such as diabetes mellitus type 2 (DM2). In this study, we analysed available genome-wide association studies (GWASs) of AD and somatic insulin-related diseases and conditions (SID), i.e., DM2, metabolic syndrome and obesity, to identify genes associated with both AD and SID that could increase our insights into their molecular underpinnings. We then performed functional enrichment analyses of these genes. Subsequently, using (additional) GWAS data, we conducted shared genetic etiology analyses between AD and SID, on the one hand, and blood and cerebrospinal fluid (CSF) metabolite levels on the other hand. Further, integrating all these analysis results with elaborate literature searches, we built a molecular landscape of the overlap between AD and SID. From the landscape, multiple functional themes emerged, including insulin signaling, estrogen signaling, synaptic transmission, lipid metabolism and tau signaling. We also found shared genetic etiologies between AD/SID and the blood/CSF levels of multiple metabolites, pointing towards “energy metabolism” as a key metabolic pathway that is affected in both AD and SID. Lastly, the landscape provided leads for putative novel drug targets for AD (including MARK4, TMEM219, FKBP5, NDUFS3 and IL34) that could be further developed into new AD treatments.