Blood Levels Research Articles

Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions.

Chemical screens across hundreds of cell lines have shown that the drug sensitivities of human cancers can vary by genotype or lineage. However, most drug discovery studies have relied on culture media that poorly reflect metabolite levels in human blood. Here, we perform drug screens in traditional and Human Plasma-Like Medium (HPLM). Sets of compounds that show conditional anticancer activity span different phases of global development and include non-oncology drugs. Comparisons of the synthetic and serum-derived components that comprise typical media trace sets of conditional phenotypes to nucleotide synthesis substrates. We also characterize a unique dual mechanism for brivudine, a compound approved for antiviral use. Brivudine selectively impairs cell growth in low folate conditions by targeting two enzymes involved in one-carbon metabolism. Cataloged gene essentiality data further suggest that conditional phenotypes for other compounds are linked to off-target effects. Our findings establish general strategies for identifying drug-nutrient interactions and mechanisms of action by exploiting conditional lethality in cancer cells.

Homocysteine Blood Levels and Mandatory Folic Acid Fortification in Serbia.

The current study aims to investigate the blood Hcy levels in patients with CAD and hypertension in Serbia, a country with a high incidence and mortality of both diseases. The level of Hcy in the Serbian population was assessed in 123 patients with chronic coronary artery disease (CAD) and hypertension. There were 53 patients with chronic CAD and 70 patients with hypertension (HTA), but without CAD. The Hcy levels were high in both groups of patients (the mean Hcy level of 16.0 ± 7.0 μmol/L) without a statistical difference between the patients in the CAD (14.9 ± 7.3 μmol/L) and hypertension (16.7 ± 6.7 μmol/L) groups. Hypercholesterolemia was found in 81% of the patients with CAD and 92.0% of the patients with HTA, as a common concern across both clinical conditions. It was also found that not a single conventional risk factor (diabetes, hypertension, the smoking status, the family history of CAD, and hyperlipidemia) may individually influence Hcy levels. By contrast, the low levels of vitamin B12 may be related to the high levels of Hcy. Given the fact that it is known that various factors interact and influence Hcy levels and associated cardiovascular risks, specific dietary habits, lifestyle and the other Serbia-specific possible factors were done.

A-281 Comparison of C-reactive Protein, Procalcitonin, and Presepsin in Blood and Synovial Fluid as Diagnostic Biomarkers for Septic Arthritis

Abstract Background Early detection and prompt treatment are crucial for managing septic arthritis (SA). However, diagnosing SA at an early stage can be challenging since the symptoms are non-specific, and there is no definitive diagnostic test available. This study aimed to investigate the potential of biomarkers as a reliable diagnostic tool for SA. Methods A prospective study was conducted to collect residual blood and synovial fluid samples from patients who underwent blood sampling and arthrocentesis for differential diagnosis due to suspected SA. The collected samples were analyzed for C-reactive protein (CRP), procalcitonin, and presepsin. The data obtained from the analysis were subjected to statistical analysis. Results From January to November 2023, 58 patients were enrolled. They comprised 24 men and 34 women with a median age of 71.1 (interquartile range, IQR 64.0-79.3) years. Twenty-one patients were diagnosed with SA and 37 with non-SA, including osteoarthritis (n=2), osteonecrosis (n=1), meniscus tear (n=1), abscess (n=1), contusion (n=2), and mechanical complications of implants (n=30). There were no significant differences in age or sex distribution between the two groups. The median blood and synovial fluid CRP levels were 4.24 and 1.85 mg/dL, respectively, in the SA group and 0.24 and 0.11 in the non-SA group. The median blood and synovial fluid procalcitonin levels were 0.0383 and 0.0403 ng/mL in the SA group and 0.0358 and 0.0488 in the non-SA group. The median blood and synovial fluid presepsin levels were 307 and 1389 pg/mL in the SA group and 192 and 959 in the non-SA group. Except for blood procalcitonin, all showed statistically significant differences between the SA and non-SA groups. In the ROC curve analysis, blood CRP displayed the highest area under the curve (AUC) of 0.795 with a 0.47 mg/dL cut-off value, 90.5% sensitivity, and 64.9% specificity. Synovial fluid CRP displayed similar results of 0.786 AUC, 0.30 mg/dL cut-off value, 85.0% sensitivity, and 71.4% specificity. Blood and synovial fluid procalcitonin had low AUCs of 0.532 and 0.659, respectively, and were insufficient to differentiate between SA and NS groups. The AUC (0.696 vs. 0.704), sensitivity (76.2% vs. 76.2%), and specificity (67.6% vs. 62.2%) of blood and synovial fluid presepsin were similar; however, synovial fluid showed a significantly higher cut-off value, 4.5 times that of blood (237 pg/mL vs. 1087 pg/mL). Conclusions Procalcitonin was not a reliable marker for distinguishing between SA and non-SA, regardless of whether it was measured in blood or synovial fluids. However, CRP and presepsin proved useful markers when measured in either blood or synovial fluid. In particular, when measuring presepsin in synovial fluid, an optimal cut-off value is needed.

Diffuse reflectance spectroscopy and RGB-imaging: a comparative study of non-invasive haemoglobin assessment

Non-invasive assessment of haemoglobin (Hb) level in blood is a hot spot in the point-of-care biomedical diagnostics. Several optical methods are suggested as a solution, some of them being approved for clinical use. Still, there is no consensus on the accuracy of optical techniques, the quality of Hb assessment on different tissue sites, and on the ability of combined use of several optical techniques to improve the quality of Hb level prediction. In this work we examined the capabilities of two optical techniques—diffuse reflectance spectroscopy and RGB-imaging of the skin and fingernails areas—in detecting low blood Hb level. The test sample consisted of 240 adult volunteers with 70 volunteers exhibiting Hb level lower than 120 g/L. We show that using simple descriptors of the diffuse reflectance spectrum of the forearm skin and fingernails is applicable for predicting low blood Hb concentration (ROC-AUC = 0.84 ± 0.08), while RGB-imaging shows similar performance when applied to the fingernail areas (ROC-AUC = 0.83 ± 0.07), which can be considered perspective for clinical use and screening properties. We also report that while the joint use of predictions from two optical methods slightly improves the accuracy of non-invasive Hb level assessment (ROC-AUC = 0.86 ± 0.07), the effect is not as high as one might expect from combining predictions of truly independent modalities, indicating the limit of the accuracy one can expect with multimodal optical approach. We review this case and propose possible solutions towards more sensitive non-invasive optical determination of hemoglobin.

Combined Effects of Environmental Metals and Physiological Stress on Lipid Dysregulation

Background: Cardiovascular diseases (CVD) are a leading cause of mortality worldwide, influenced by genetic, environmental, and behavioral factors. This study examines the relationship between heavy metal exposure, chronic physiological stress (allostatic load), and lipid profiles, which are markers of CVD risk, using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018. Methods: We utilized structural equation modeling (SEM) to explore the associations between blood levels of lead, cadmium, allostatic load (AL), and lipid measures (low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides). The AL index was derived from cardiovascular, inflammatory, and metabolic biomarkers and categorized into quartiles to identify high-risk individuals, with an index out of 10 subsequently developed. Results: The SEM analysis revealed that both heavy metal exposure and allostatic load are significantly associated with lipid profiles. Higher levels of lead and cadmium were associated with increased LDL and triglycerides, while higher AL scores were linked to increased LDL and triglycerides and decreased HDL levels. Age was also a significant factor, showing positive correlations with LDL and triglycerides, and a negative correlation with HDL. Conclusions: This study underscores the multifactorial nature of CVD, highlighting the combined impact of environmental pollutants and physiological stress on lipid dysregulation. These findings suggest the need for integrated public health strategies that address both environmental exposures and chronic stress to mitigate cardiovascular risk. Further research is warranted to explore the underlying mechanisms and develop targeted interventions.

B-258 Rapid clozapine blood levels on the Beckman Coulter DxC 500 AU

Abstract Background Clozapine is the most effective drug for treatment-resistant schizophrenia. Multiple guidelines strongly recommend clozapine therapeutic drug monitoring (TDM). Measuring clozapine blood levels provides essential information when there are questions of medication adherence, efficacy, toxicity, medication interactions, or concern over other factors that may influence clozapine levels. Turnaround time is essential for effective clinical decisions. However, with liquid-chromatography/mass spectrometry, clozapine levels can take days to report results. To address the medical need for a faster turnaround time, a rapid clozapine immunoassay was developed for automated clinical chemistry analyzers. The immunoassay measuring range is based on established APA Practice Guidelines and ASCP/AGNP Consensus Statement. We developed an analyzer application for the DxC 500 AU (time to first result < 9 minutes) to expand the availability of rapid clozapine blood level testing. Methods The performance of the FDA-cleared clozapine assay was evaluated on the DxC 500 AU according to CLSI guidelines. Precision testing was performed with three clozapine spiked pools over five days with five replicates per sample. Precision sample recovery was assessed to their theoretical spike concentration. Linearity was verified with five spiked serum samples covering the measuring range. Method comparison was performed with 40 remnant patient samples vs. the Beckman Coulter AU480. Results Repeatability CV was ≤5.5% and within-laboratory precision CV was ≤6.1%. Individual deviation was ±20% and mean deviation was ±2% for all samples. Deviation from linearity was <3%. Deming regression statistics for the method comparison were a slope of 0.987, an intercept of 5.7, and an R of 0.9948. The methods are statistically equivalent: the 99% confidence limits contained 1 and 0 for the slope and intercept respectively. Conclusions The precision, recovery, linearity, and method comparison results for clozapine on the DxC 500 AU demonstrate that the analyzer can be used to generate robust results for clozapine.

Circulating levels of micronutrients and risk of osteomyelitis: a Mendelian randomization study

BackgroundFew observational studies have investigated the effect of micronutrients on osteomyelitis, and these findings are limited by confounding and conflicting results. Therefore, we conducted Mendelian randomization (MR) analyses to evaluate the association between blood levels of eight micronutrients (copper, selenium, zinc, vitamin B12, vitamin C, and vitamin D, vitamin B6, vitamin E) and the risk of osteomyelitis.MethodsWe performed the two-sample and multivariable Mendelian randomization (MVMR) to investigate causation, where instrument variables for the predictor (micronutrients) were derived from the summary data of micronutrients from independent cohorts of European ancestry. The outcome instrumental variables were used from the summary data of European-ancestry individuals (n = 486,484). The threshold of statistical significance was set at p < 0.00625.ResultsWe found a significant causal association that elevated zinc heightens the risk of developing osteomyelitis in European ancestry individuals OR = 1.23 [95% confidence interval (CI) [1.07, 1.43]; p = 4.26E-03]. Similarly, vitamin B6 showed a similar significant causal effect on osteomyelitis as a risk factor OR = 2.78 (95% CI [1.34, 5.76]; p = 6.04E-03; in the secondary analysis). Post-hoc analysis suggested this result (vitamin B6). However, the multivariable Mendelian randomization (MVMR) provides evidence against the causal association between zinc and osteomyelitis OR = 0.98(95% CI [−0.11, 0.07]; p = 7.20E-1). After searching in PhenoScanner, no SNP with confounding factors was found in the analysis of vitamin B6. There was no evidence of a reverse causal impact of osteomyelitis on zinc and vitamin B6.ConclusionThis study supported a strong causal association between vitamin B6 and osteomyelitis while reporting a dubious causal association between zinc and osteomyelitis.

B-323 Measurement of PIVIKA II Blood Level in Patients with Liver Diseases by Immunoassays

Abstract Background Liver diseases are the most common diseases globally and can be complicated to cirrhosis and cancer and lead to death if not managed. It is crucial to prevent patients with liver diseases to reach the level of complications in particular liver cancer or hepatocellular Carcinoma (HCC). There are many screening lab tests to monitor and evaluate patients with liver disease such as alpha fetoprotein (AFP), however, it lacks optimal sensitivity and specificity. Another promising screening test is Prothrombin Induced by Vitamin K deficiency or antagonist- II (PIVKA-II) to complements AFP in screening of HCC. The aim of this study was to evaluate two PIVKA-II immunoassays and compare it to AFP in blood samples of patients with liver diseases. Methods Blood samples were collected from 56 patients with liver diseases, chronic hepatitis B (n=14), chronic hepatitis C (n=18), liver cirrhosis (n=14), and HCC (n=10) at King Abdulaziz medical city, Riyadh, SA. Measurement of PIVKA-II levels were performed on all samples by Snibe and Abbott analyzers. Clinical data was collected from the HIS BestCare. AFP was performed on Abbott analyzer. Statistical analysis was carried by Excel sheet Microsoft and p value was set at 0.05. Results There was an excellent correlation (R2= 0.9327) between the PIVKA-II two immunoassays from Snibe and Abbott among patients with HCC (p=0.1384). The diagnostic sensitivity PIVKA-II for Abbott and Snibe were calculated to be 78% and 90% respectively among HCC patients at cutoff 32 mAU/mL with specificity of 16% and 44.4% respectively. This was corresponding to sensitivity of 90% and specificity of 67% on AFP at cutoff 10 ng/mL. Conclusions The two PIVKA-II two immunoassays were perfectly correlated among the samples of HCC patients. The sensitivity of both assays was high but with lower specificity. Snibe assay has superior sensitivity and specificity among patients with HCC.

B-222 Receptor-donor CYP3A5 and CYP3A4 genotype testing in liver transplant patients and its influence in tacrolimus blood levels: a retrospective study

Abstract Background Optimal immunosupression is crucial for transplant success. In orthohepatic transplants, blood target levels of tacrolimus, when coadministred with corticoids and mycophenolic acid, are between 6 and 10 ng/mL during the first three months post-transplant. Notwithstanding, achieving tacrolimus concentrations into this range may be tough because of factors such as liver function status, age, sex, drug-drug interactions, etc. In this way, pharmacogenetic testing of CYP3A5 and CYP3A4 genes have demonstrated to be useful in tacrolimus dosing optimization. Nonetheless, there is no evidence enough for pharmacogenetic based adjusting in liver transplant, specially if receptor and graft’s genotypes differ in these loci. The aim of the present study is to find out how the receptor and donor genotypes in CYP3A5 and CYP3A4 genes affect tacrolimus pharmacokinetics. Methods Genotypic profiling of 108 receptor-donor's pairs biopsies gathered from patients who were underwent hepatic transplant from 2012 to 2019 were carried out using Taqman® OpenArray™ PGx Express 120 panel (ThermoFisher™). We focused on CYP3A5*3, *6 and *7; and CYP3A4*1B, *3 and *22 alleles. Next to pharmacogenetic testing, each patient was classified as very poor, poor, intermediate, rapid or ultrarapid metabolizer according to their own genotype, graft’s genotype or both of them. Patient’s initial dose, at seven days after treatment start and after discharge of tacrolimus and their trough concentrations (C0) were collected from their electronic health records. Tacrolimus levels were measured by affinity chrome-mediated immunoassay. C0 was normalized by weight-adjusted dosage (C/D ratio); then, median C/D ratios between different metabolic profiles were compared through Kruskal-Wallis test. Results When patients were classified based on donor’s genotype isolated or combined with receptor’s genotype, lower C/D ratios were found as metabolizer ability increases (p=0.045 for donors and p=0.027 for combined genotypes, respectively). No statistically differences were found for C/D ratios at seven days and discharge, though that differences were almost significant for donor’s genotypes (p=0.06 in both cases). Conclusions These results show that previous information about both patient’s and specially donor’s CYP genes genotype may improve initial immunosupression and avoid tacrolimus induced toxicity. Pharmacogenetics has been currently proposed as a guide for tacrolimus treatment of some solid organ transplants as kidney transplanted patients. Better understanding of how receptor and donor’s CYP genotype affects its pharmacokinetics, along with liver’s damage markers and other genetic polymorphisms will allow clinicians, in the era of personalized medicine, to improve immunosupressive management.

B-303 Stability of Antipsychotic Drugs in Patient Serum and Plasma Clinical Samples

Abstract Background Therapeutic drug monitoring (TDM) of antipsychotic blood levels is strongly recommended (clozapine and olanzapine) and recommended (risperidone, aripiprazole, and quetiapine) by ASCP/AGNP Consensus Statement. For effective TDM, it is paramount to understand both the stability of the antipsychotic drugs in serum and plasma, as well as any differences in levels due to sample matrix to ensure robust concentration determinations. While clozapine levels are considered equivalent in serum and plasma, we included in our study four additional antipsychotics. Methods Whole blood samples from ten patients taking clozapine, risperidone, aripiprazole, olanzapine, or quetiapine were collected in one red top tube and in one purple top tube according to an IRB-approved protocol. Samples were then processed within 2 hours of collection to obtain matched serum and K2EDTA plasma samples from each of the patients. CE marked immunoassays for the measurement of clozapine (also FDA cleared), total risperidone/paliperidone, total aripiprazole, olanzapine, and quetiapine were used to quantitate drug concentrations. Stability of the samples was assessed at 4°C, ambient room temperature (ART), and frozen at -80°C, with respect to their Day 0 concentration by measurement of six replicates at each timepoint using the immunoassays. Results Comparison of Day 0 values between serum and plasma for the same patient showed ±9% bias between sample matrices for all drugs, except olanzapine which showed differences up to ±15%. Average bias between serum and plasma was ≤-5% (olanzapine: -9%). All drugs were stable (±15% deviation from Day 0; olanzapine up to ±23%) in serum and in plasma for 7 days at both 4°C and ART and for up to 8 months frozen. Conclusions This study demonstrated that (1) the antipsychotic drugs clozapine, risperidone, aripiprazole, olanzapine, and quetiapine have sufficient stability in both serum and plasma for effective TDM and (2) for TDM, serum or plasma may be used.

Therapeutic Hydroxychloroquine Blood Levels Are Associated With Fewer Hospitalizations and Possible Reduction of Health Disparities in Lupus.

Nonadherence to receiving hydroxychloroquine (HCQ) is associated with a three-fold higher risk of lupus-related hospitalization. Monitoring HCQ blood levels could improve adherence to receiving HCQ and efficacy. Yet, HCQ level monitoring is not routinely done partially due to cost and coverage concerns. To establish HCQ level monitoring cost-effectiveness, we reported the following: (1) risk of acute care by HCQ blood levels, and (2) cost of HCQ monitoring versus acute care visits. HCQ blood levels were measured during routine lupus visits. HCQ levels were categorized as follows: (1) subtherapeutic (<750 ng/mL), (2) therapeutic (750-1,200 ng/mL), or (3) supratherapeutic (>1,200 ng/mL). All lupus-related acute care visits (emergency room visits/hospitalizations) after the index clinic visit until next follow-up were abstracted. In our primary analysis, we examined associations between HCQ levels and time to first acute care visit in all patients and subgroups with higher rates of acute care. A total of 39 lupus-related acute care visits were observed in 181 patients. Therapeutic HCQ blood levels were associated with 66% lower rates of acute care. In our cohort, two groups, Black or Hispanic patients and those with public insurance, faced three to four times higher rates of acute care. Levels within 750 to 1,200 ng/mL were associated with 95% lower rates of acute care use in subgroups with higher acute care use. HCQ blood levels within 750 to 1,200 ng/mL are associated with lower rates of acute care in all patients with lupus, including groups with higher rates of acute care. Future clinical trials should establish the causal association between HCQ level monitoring and acute care in patients with lupus.

Long non‑coding RNAs as diagnostic and prognostic biomarkers for colorectal cancer (Review).

Colorectal cancer (CRC) ranks as the 3rd most common cancer globally and is the 2nd leading cause of cancer-related death. Owing to the lack of specific early symptoms and the limitations of existing early diagnostic methods, most patients with CRC are diagnosed at advanced stages. To overcome these challenges, researchers have increasingly focused on molecular biomarkers, with particular interest in long non-coding RNAs (lncRNAs). These non-protein-coding RNAs, which exceed 200 nucleotides in length, play critical roles in the development and progression of CRC. The stability and detectability of lncRNAs in the circulatory system make them promising candidate biomarkers. The analysis of circulating lncRNAs in peripheral blood represents a potential option for minimally invasive diagnostic tests based on liquid biopsy samples. The present review aimed to evaluate the efficacy of lncRNAs with altered expression levels in peripheral blood as diagnostic markers for CRC. Additionally, the clinical significance of lncRNAs as prognostic markers for this disease were summarized.

Characteristics of Psychoemotional Manifestations of Laboratory Rodents Undergoing Surgery when Modeling Preoperative Stress.

We studied psychoemotional characteristics and the blood level of corticosterone in sexually mature male C57BL/6 mice (n=40): intact (control), after simulating preoperative stress and surgery, after surgery, and after anesthesia alone. It was found that the anxiety index calculated on the basis of testing in the elevated plus maze was significantly higher in both groups of operated animals. The mice of both operated groups and animals exposed to anesthesia alone showed increased anxiety. Symptoms indicating a high probability of transition of anxiety into a psychoemotional disorder have been recorded.

Blood levels of branched chain amino acids and sleep: A cross-sectional study

Blood levels of branched chain amino acids and sleep: A cross-sectional study

Correlation between prognosis and peripheral blood levels of NLRP3 and triglyceride-glucose index after myocardial ischemia-reperfusion injury

ObjectiveWe aim to investigate the association between prognosis and outcomes following myocardial ischemia-reperfusion injury, as well as peripheral blood levels of NLRP3 and the triglyceride-glucose index (TyG).MethodsA total of 100 patients who underwent emergency coronary intervention following myocardial infarction confirmed by coronary angiography at our hospital between October 2021 and May 2023 were included in this study. Patients were stratified into two groups based on their prognoses: the control group (n = 73), which did not experience new myocardial infarctions or require hospitalization for heart failure or suffer sudden cardiac death post-interventional treatment; and the observation group (n = 27), which experienced one or more cardiovascular events post-treatment. Patient demographics were obtained from clinical records while biochemical analyses assessed peripheral blood triglycerides, blood glucose levels, and TyG index. Additionally, ELISA measurements determined levels of NLRP3 as well as inflammatory factors IL-6, TNF-α, and CRP in peripheral blood samples. Cardiac function was evaluated according to NYHA standards. Univariable Cox regression analysis identified factors influencing patient prognosis while Pearson correlation analysis examined relationships among prognosis, outcomes following myocardial ischemia-reperfusion injury, TyG index, and peripheral blood NLRP3.ResultsNo significant differences were observed in the general characteristics between the two patient groups (P > 0.05). However, the observation group exhibited higher levels of peripheral blood triglycerides, blood glucose, and TyG index compared to the control group (P < 0.05). Additionally, levels of NLRP3 and inflammatory factors IL-6, TNF-α, and CRP were elevated in the observation group compared to the control group (P < 0.05). Cardiac function impairment was more pronounced in the observation group (P < 0.05). Notably, TyG index and peripheral blood NLRP3 demonstrated higher risk ratios compared to other biomarkers (P < 0.05), indicating their significance in prognosis and outcomes. Elevated levels of NLRP3 and TyG index were associated with poorer recovery of cardiac function, increased rehospitalization rates, and higher mortality (P < 0.05).ConclusionElevated NLRP3 levels and an increased TyG index are strongly associated with impaired cardiac function and heightened risk of cardiovascular events. These findings suggest that these biomarkers may serve as crucial prognostic indicators following myocardial ischemia-reperfusion injury.

Data-Driven Clinical Pharmacy Research: Utilizing Machine Learning and Medical Big Data.

To conduct clinical pharmacy research, we often face the limitations of conventional statistical methods and single-center observational study. To overcome these issues, we have conducted data-driven research using machine learning methods and medical big data. Decision tree analysis, one of the typical machine learning methods, has a flowchart-like structure that allows users to easily and quantitatively evaluate the occurrence percentage of events due to the combination of multiple factors by answering related questions with Yes or No. Using this feature, we first developed a risk prediction model for acute kidney injury caused by vancomycin, a condition we frequently encounter in clinical practice. Additionally, by replacing the prediction target from a binary variable (i.e., presence or absence of adverse drug reactions) to a continuous variable (i.e., drug dosage), we built a model to estimate the initial dose of vancomycin required to reach the optimal blood level recommended by guidelines. We found its accuracy to be better than that of conventional dose-setting algorithms. Moreover, employing Japanese medical big data such as the claims database helped us overcome the major limitations of conventional clinical pharmacy research such as institutional bias caused by single-center studies. We demonstrated that the combined use of machine learning and medical big data could generate high-quality evidence leveraging the strengths of each approach. Data-driven clinical pharmacy research using machine learning and medical big data has enabled researchers to surpass the limitations of conventional research and produce clinically valuable findings.

Assessment of B2-Microglobulin Analysis for Renal Insufficiency in Iraqi β-Thalassemia Major Patients

Background: Beta-thalassemia is the most prevalent genetic hemoglobin apathy in the world. It is caused by a reduction or absence of beta-globin chain production, which is typically a portion of adult hemoglobin (HbA, which is α2β2). This genetic anomaly will lead to a rapid erythrocyte turnover, severe anemia, and compensatory ineffective erythropoiesis. The purpose of the current research is to reveal diagnostic, and predictive biomarkers that can be performed to detect the decline in renal function in β-thalassemia major patients with early stage renal impairment with high sensitivity and specificity, ascertain changes in B2-microglobulin as a biomarker in β-thalassemia patient. Objective: The samples were collected from Karama Hospital-Genetic Hematology Center/Baghdad during the period from the 1st of September 2022 until the 1st of January 2023. Methods: The patient group consisted of 45 patients with β-thalassemia major with repeated blood transfusion and the control group consisted of 45 individuals who seemed to be healthy. Age ranged between (18-35) years (for patients and control). The serum samples were used to measure biochemical parameters, S.Creatinine, blood urea, and Urine B2-microglobulin were measured from urine samples. B2-microglobulin level in Urine was estimated by Sandwich enzyme-linked immunosorbent assay (ELISA) technique, while serum Blood Urea and Serum Creatinine concentration were calculated by Colorimetric Kit by Spectrophotometer method, and Ferritin level in blood was estimated by BioMrieux Mini Vidas. Results: The statistical examination was carried out using SPSS software. B2-microglobulin biomarkers in the thalassemia Patient group were significantly higher than those in the control group (p&lt;0.001). While serum ferritin, B.Urea and S.Cr increased in patient groups compared to the control group (p&lt;0. 005). Conclusions: All parameters included in this study are significantly higher in β-thalassemia patients than in healthy subjects. Renal hemosiderosis and asymptomatic renal dysfunction are prevalent among β-thalassemia major patients with repeated blood transfusions, which are not found in routine renal investigations.

Beyond the Gender Binarism: Neural Correlates of Trans Men in a Functional Connectivity–Resting-State fMRI Pilot Study

Introduction: Several studies have investigated the specific neural correlates of trans people, highlighting mixed results. This study aimed to compare the presence of specific functional connectivity and differences in cognitive profile and hormone levels in trans men diagnosed with gender dysphoria (GD), and a homogeneous group of cisgender men and cisgender women. Methods: A total of 42 participants (19 trans men, 11 cisgender men, and 12 cisgender women) underwent a resting state fMRI and were measured for blood levels of testosterone, estradiol, and progesterone. A neuropsychological battery evaluated executive functions, attention, visual-perceptual ability, verbal fluency, manual preference, and general intelligence. Results: Trans men showed weaker functional connectivity in the precentral gyrus, subcallosal cortex, paracingulate gyrus, temporal pole, and cingulate gyrus than cisgender men (p &lt; 0.01). Trans men performed worse than cisgender men in verbal and visuospatial working memory but similarly to cisgender women (p &lt; 0.05). In trans men, functional connectivity of the precentral gyrus correlated positively with testosterone (r = 0.459, p = 0.064) and negatively with estradiol (r = −0.654, p = 0.004) and progesterone blood levels (r = −0.475, p = 0.054). The cluster involving the subcallosal cortex showed a positive correlation with testosterone (r = 0.718, p = 0.001), and a negative correlation with estradiol (r = −0.602, p = 0.011). The functional connectivity from a cluster involving the paracingulate gyrus showed a positive correlation with testosterone (r = 0.592, p = 0.012). Conclusions: This study highlights the importance of overpassing the binary model by underlining the presence of neural pathways that could represent the peculiarity of the neural profile of people with GD.

Emerging Trends: Neurofilament Biomarkers in Precision Neurology.

Neurofilaments are structural proteins found in the cytoplasm of neurons, particularly in axons, providing structural support and stability to the axon. They consist of multiple subunits, including NF-H, NF-M, and NF-L, which form long filaments along the axon's length. Neurofilaments are crucial for maintaining the shape and integrity of neurons, promoting axonal transport, and regulating neuronal function. They are part of the intermediate filament (IF) family, which has approximately 70 tissue-specific genes. This diversity allows for a customizable cytoplasmic meshwork, adapting to the unique structural demands of different tissues and cell types. Neurofilament proteins show increased levels in both cerebrospinal fluid (CSF) and blood after neuroaxonal damage, indicating injury regardless of the underlying etiology. Precise measurement and long-term monitoring of damage are necessary for determining prognosis, assessing disease activity, tracking therapeutic responses, and creating treatments. These investigations contribute to our understanding of the importance of proper NF composition in fundamental neuronal processes and have implications for neurological disorders associated with NF abnormalities along with its alteration in different animal and human models. Here in this review, we have highlighted various neurological disorders such as Alzheimer's, Parkinson's, Huntington's, Dementia, and paved the way to use neurofilament as a marker in managing neurological disorders.

Effect of mixed probiotics on pulmonary flora in patients with mechanical ventilation: an exploratory randomized intervention study

ObjectiveThe study objective was to investigate the effect of mixed probiotics on the diversity of the pulmonary flora in critically ill patients requiring mechanical ventilation by analysing the changes in lung microbes.Methods24 adult critically ill patients who needed mechanical ventilation in our hospital were randomly divided into a probiotic group and a control group. Then, the probiotic group was given Live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules, Oral (Bifico) by nasal feeding within 24 h after mechanical ventilation. Bronchoalveolar lavage fluid (BALF) and venous blood were collected within 24 h after mechanical ventilation and on the 5th day after mechanical ventilation, and the treatment status of patients (mechanical ventilation time, 28-day survival), measured cytokine levels (IL-1 β, IL-6, IL-8, IL-17A) and changes in pulmonary microorganisms were observed.ResultsThe microbial diversity of BALF samples decreased in the control group, and there was no significant difference in the probiotic group. Species difference analysis showed that among the three probiotics (Bifidobacterium, Lactobacillus, Enterococcus) used for intervention, Lactobacillus caused significant differences in BALF in the control group. Clinical factor association analysis displayed significant associations with IL-17A levels in both blood and BALF.ConclusionMechanical ventilation can cause a decline in pulmonary microbial diversity, which can be improved by administering mixed probiotics.