Increased MCHC*RDW-SD interaction values: indicators of neurological impairment in lead-poisoned children.

Background: The neurotoxic effects of lead in children can have long-lasting and profound impacts on the developing nervous system. This study aimed to identify a reliable and easily accessible biomarker to monitor neurological impairment in lead-poisoned children. Methods: We analyzed hematological data from 356 lead-poisoned children, comparing them with age and gender-matched healthy controls. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were employed to identify and evaluate potential biomarkers for neurological damage. Results: Significant changes in erythrocyte parameters were observed in lead-poisoned children. Upon further analysis, increased mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width-standard deviation (RDW-SD) interaction values were found to be significantly associated with neurological impairment. The MCHC*RDW-SD interaction model demonstrated an AUC of 0.76, indicating its effectiveness in reflecting neurological damage. Additionally, the MCHC*RDW-SD Interaction value showed weak or no correlation with other erythrocyte parameters, suggesting its independence as an indicator. Conclusion: Our findings propose the increased MCHC*RDW-SD interaction value as a robust and independent biomarker for detecting neurological impairment in lead-poisoned children. This underscores the potential of utilizing specific erythrocyte parameters for screening the neurotoxic effects of lead exposure in pediatric populations.

Platelet count and MCHC as independent prognostic markers for feline mammary carcinomas.

Mammary neoplasms are common in felines species and represent a significant disease for its unfavorable prognosis. Changes in the blood count and serum biochemical profile of these patients have potential as non-invasive prognostic markers prior to mastectomy, however, they are poorly described in literature. In this study univariate and multivariate analyses were performed using these factors to determine the effect of each parameter on the one-year survival time after the surgical procedure in these animals. The median overall survival (OS) and the disease-free survival (DFS) were 365 and 242 days, respectively. In univariate analysis, values within the reference range of monocyte, platelet and creatinine counts were identified as significant prognostic factors for OS and only creatinine was significant for DFS (P < 0.05). In the multivariate analysis, platelets and mean corpuscular hemoglobin concentration (MCHC) remained independent prognostic factors for OS. The results presented suggest that monocytes, platelets and creatinine may be important non-invasive pre-surgical prognostic markers, and that platelet count and MCHC are independent prognostic markers for feline mammary carcinomas (FMC). The correlation between such alterations is of important relevance for veterinary oncology, and prospective studies are needed to validate their clinical use and that platelet count and MCHC are independent prognostic markers for FMC. The results found in this study can also be studied in human medicine, regarding blood markers in human breast cancer (HBC).

Improving the diagnosis of myelodysplastic syndrome by red blood cell parameters

Purpose To investigate the value of red blood cell parameters in Myelodysplastic syndrome (MDS) diagnosis and their relations to MDS subtypes and risk groups. Methods The red blood cell parameter [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)] levels [203 MDS, 99 aplastic anemia (AA), 145 megaloblastic anemia (MA)] were collected from a single-center retrospective cohort. The cut-off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of the four parameters were calculated from the ROC. Furthermore, Kruskal–Wallis test and Dunn’s Test were performed to determine erythrocyte parameters in different subtypes and prognostic risks MDS. Results There are significant statistic differences in RDW (P < 0.001), MCH (P = 0.036) and MCHC (P < 0.001) (MDS vs AA); RDW (P = 0.009), MCV (P < 0.001), MCH (P < 0.001) and MCHC (P = 0.001) (MDS vs MA); MCV (P = 0.011) and MCH (P = 0.008) (higher-risk MDS vs lower-risk MDS). Between MDS and MA, the area under the receiver operating characteristic curve (ROC) curve (AUC) values of MCV, MCH, MCHC, RDW were 0.846, 0.855, 0.617, and 0.593. Between MDS and AA, the AUC values of MCH, MCHC, RDW were 0.609, 0.671, and 0.662, respectively. Conclusions The red blood cell parameters contribute to the differential diagnosis of MDS, AA and MA and are related to MDS subtypes and risk groups (AU)

Quantifying microcyte and macrocyte percentages in archived red blood cell volume histogram images.

INTRODUCTION: We sought to quantify percentages of microcytes and macrocytes in archived automated hematology analyzer (AHA) red blood cell (RBC) volume histogram images. METHODS: In preliminary studies, we demonstrated that an on-line application of Gauss' area formula (SketchAndCalc™) measured percentage areas of 20 segments under a computer-generated normal distribution curve (-3.0 standard deviations [SD] to +3.0 SD) with accuracy and precision (Pearson's correlation of measured areas with corresponding theoretical areas r [20] = 0.9962 [p < 0.0001]). Thus, we used SketchAndCalc™ to quantify percentages of microcytes (50-80 fL) and macrocytes (110-200 fL) in archived AHA histogram images in women with previously untreated iron-deficiency anemia (IDA) and previously untreated hemochromatosis. RESULTS: Median microcyte percentages in 13 women with IDA and 13 women with hemochromatosis were 63.6% (range 13.5-76.8) and 6.7% (range 3.4-24.8), respectively (p < 0.0001). Mean macrocyte percentages in women with IDA and hemochromatosis were 8.8% ± 6.1 SD and 33.8% ± 11.7 SD, respectively (p < 0.0001). Spearman's correlations of microcyte percentages with macrocyte percentages, mean corpuscular volume, and mean corpuscular hemoglobin in 26 women were rs [26] = -0.9485, rs [26] = -0.9641, and rs [26] = -0.9036, respectively (each p < 0.0001). CONCLUSIONS: This method of quantifying microcyte and macrocyte percentages could enable other studies of RBC volume subpopulations in archived AHA histogram images.

The Clinical Usefulness of Mean Corpuscular Hemoglobin Concentration in Patients with Pneumoconiosis.

Aim: We investigated the clinical usefulness of mean corpuscular hemoglobin concentration (MCHC) in patients with pneumoconiosis. Methods: We retrospectively investigated the medical records from 52 patients with pneumoconiosis, and erythrocyte parameters were analyzed in pneumoconiosis patients with different stages. Results: Here, we found that the values of MCHC were significantly lower in III stage pneumoconiosis than those with I/II stage (p = 0.024), and there was no significantly difference in MCHC between smoking pneumoconiosis patients and non-smoking pneumoconiosis patients. A negatively correlation between MCHC and disease stage was observed in patients with pneumoconiosis (r = -0.298, p = 0.032). In multiple linear regression analysis, the MCHC was found to be independently associated with advanced pneumoconiosis in patients with pneumoconiosis (p=0.011). The results of logistic regression analysis indicated that decreased MCHC was an independent risk factor of advanced pneumoconiosis in patients with pneumoconiosis (OR: 0.936, CI95%: 0.877-0.999, p = 0.046). Receiver operating characteristic curve analysis showed that the optimal cutoff value of MCHC was 330 g/L to identify advanced pneumoconiosis with the area under the curve of 0.694 (CI95%:0.550-0.839, p = 0.018). Conclusion: The decreased MCHC is associated with advanced pneumoconiosis, and MCHC may be used as a monitoring marker for follow-up of pneumoconiosis patients.

Improving the diagnosis of myelodysplastic syndrome by red blood cell parameters.

PURPOSE: To investigate the value of red blood cell parameters in Myelodysplastic syndrome (MDS) diagnosis and their relations to MDS subtypes and risk groups. METHODS: The red blood cell parameter [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)] levels [203 MDS, 99 aplastic anemia (AA), 145 megaloblastic anemia (MA)] were collected from a single-center retrospective cohort. The cut-off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of the four parameters were calculated from the ROC. Furthermore, Kruskal-Wallis test and Dunn's Test were performed to determine erythrocyte parameters in different subtypes and prognostic risks MDS. RESULTS: There are significant statistic differences in RDW (P < 0.001), MCH (P = 0.036) and MCHC (P < 0.001) (MDS vs AA); RDW (P = 0.009), MCV (P < 0.001), MCH (P < 0.001) and MCHC (P = 0.001) (MDS vs MA); MCV (P = 0.011) and MCH (P = 0.008) (higher-risk MDS vs lower-risk MDS). Between MDS and MA, the area under the receiver operating characteristic curve (ROC) curve (AUC) values of MCV, MCH, MCHC, RDW were 0.846, 0.855, 0.617, and 0.593. Between MDS and AA, the AUC values of MCH, MCHC, RDW were 0.609, 0.671, and 0.662, respectively. CONCLUSIONS: The red blood cell parameters contribute to the differential diagnosis of MDS, AA and MA and are related to MDS subtypes and risk groups.

The influence of serial 50 µL microsampling on rats administered azathioprine, the immunosuppressive drug.

According to the ICH S3A Q&A, microsampling is applicable to pharmaceutical drugs and toxicological analysis. Few studies have reported the effect of microsampling on the toxicity of immunotoxicological drugs. The aim of this multicenter study was to evaluate the toxicological effects of serial microsampling on rats treated with azathioprine as a model drug with immunotoxic effects. Fifty microliters of blood were collected from the jugular vein of Sprague-Dawley rats at six time points from day 1 to 2 and 7 time points from day 27 to 28. The study was performed at three organizations independently. The microsampling effect on clinical signs, body weights, food consumption, hematological parameters, biochemical parameters, urinary parameters, organ weights, and tissue pathology was evaluated. Azathioprine-induced changes were observed in certain hematological and biochemical parameters and thymus weight and pathology. Microsampling produced minimal or no effects on almost all parameters; however, at 2 organizations, azathioprine-induced changes were apparently masked for two leukocytic, one coagulation, and two biochemical parameters. In conclusion, azathioprine toxicity could be assessed appropriately as overall profiles even with blood microsampling. However, microsampling may influence azathioprine-induced changes in certain parameters, especially leukocytic parameters, and its usage should be carefully considered.

Impact of age-dependent red blood cell parameters on α-globin gene genotyping in children.

When screening for α-thalassemia in children, adult cut-offs for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) are generally applied to guide genetic evaluation. However, the normal ranges for MCV and MCH are lower in children than in adults, so we hypothesized that using age-matched cut-offs could lead to a more rational diagnostic strategy. The aim of this study was to evaluate if age-matched cut-offs could be applied advantageously. Data on children referred to a hemoglobin fractionation at the Department of Clinical Biochemistry, Aarhus University Hospital between 2016-2021 were identified in the laboratory information system. α-globin gene (HBA1/HBA2) genotyping was performed using multiplex gap-polymerase chain reaction. A total of 387 children were identified. HBA1/HBA2-genotyping was performed in 207 children (53%), and α-thalassemia was diagnosed in 47 children (23%) with -α3.7/αα being the predominant genotype (13%). We found that 23 children had MCV and MCH levels in the normal age-matched range, and two of these children (9%) were α+ thalassemia carriers with three functional α-globin genes. Using age-specific cut-off levels resulted in a reduction of 23 (11%) genotypes performed. In conclusion, applying age-matched cut-offs for MCV and MCH when screening children for α-thalassemia lead to 11% fewer genotypes performed while 9% carriers of α+ thalassemia (of the medically innocuous genotype -α3.7/αα) would have been overlooked.

The association between serum ferritin and bilirubin with glycemic control among patients with type 2 diabetes mellitus.

Previous evidence has shown an association between serum ferritin and bilirubin levels in the development of type 2 diabetes mellitus (T2DM) and glycemic control. However, the evidence is scarce in Saudi Arabia. In this study, we aimed to evaluate the association between serum ferritin and bilirubin levels with glycemic control in patients with T2DM. This was a cross-sectional study that involved 153 patients with T2DM recruited from outpatient diabetes clinics. Participants were categorized into two groups: well-controlled and uncontrolled T2DM, based on their glycemic status. We focused on comparing the iron profile and bilirubin levels between these two groups and examining the influence of antidiabetic medications on these parameters. A total of 153 patients with T2DM were included (58.2% women and 41.8% men). In both univariate and multivariate analyses, ferritin levels did not have a statistically significant association with glycemic control. However, patients with well-controlled T2DM had a significantly higher median level of total bilirubin and direct bilirubin than those with uncontrolled T2DM. Only direct bilirubin showed a statistically significant association with FBG less than 130 mg/dl and HbA1c level less than 7.0%. Ferritin level was not associated with glycemic control in patients with T2DM. On the other hand, direct bilirubin level was an independent predictor of better glycemic control. Monitoring direct bilirubin levels could aid in predicting glycemic control in T2DM and could be a potential target for developing antidiabetic medications.

Evaluation and optimization of pre-pregnancy and pregnancy thalassaemia screening programmes in Hainan Province / 中国热带医学

@#Abstract: Objective　To evaluate the free thalassaemia screening programme for preconception and pregnancy in Hainan Province, and to provide a theoretical basis for optimizing the screening process for thalassaemia. Methods From November 2020 to July 2021, a survey was conducted on 10 396 adults with Hainan household registration who participated in the Epidemiological Survey of Thalassemia in Hainan Residents in 19 cities and counties of Hainan Province. All of them underwent routine blood tests, haemoglobin electrophoresis tests and genetic tests for thalassaemia. The optimal diagnostic cut-off values for mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and haemoglobin adult type 2 (HbA2) were determined using screening test indexes such as receiver operating characteristic curve and sensitivity. The diagnostic effectiveness of different primary screening programs for thalassemia gene carriers was evaluated. Results Using the existing MCV single-indicator thalassemia primary screening protocol in Hainan Province, where individuals with MCV<82 fL undergo thalassemia gene testing, resulted in a high missed diagnosis rate (34.06%) and low sensitivity (65.94%). The optimal cut-off values for MCV screening for alpha-and beta-thalassaemia were 84.45 fL and 79.05 fL, respectively; the optimal cut-off values for MCH screening for alpha-and beta-thalassaemia were 27.95 pg and 25.15 pg, respectively. The optimal cut-off value for HbA2 screening for alpha-thalassaemia was less than 2.55% and greater than 3.35% for beta-thalassaemia. The "combined HbA2 or MCH or MCV screening protocol" with the cut-off values recommended in this study had a better performance in primary screening for thalassemia, with the highest sensitivity (92.96%) and negative predictive value (92.67%) and the lowest underdiagnosis rate (7.04%), statistically significant differences compared with the existing protocol (P<0.05). Conclusions The current process of screening for thalassemia in Hainan Province may lead to missed diagnoses. The combined use of MCV, MCH and HbA2 for thalassemia screening, adopting locally suitable cutoff values for primary screening indicators, can improve the incidence of missed reporting of thalassemia and enhance diagnostic effectiveness.

Comparison of the red blood cell indices based on accuracy, sensitivity, and specificity to predict one-year mortality in heart failure patients.

BACKGROUND: Various investigations have specified the role of each RBC indices separately [including hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW)] to predict the prognosis of acute heart failure (AHF) patients. However, in the current study, these variables were compared based on accuracy, sensitivity, and specificity to determine the best prognostic factor. METHODS: Of 734 heart failure patients referred to the emergency department, 400 cases were enrolled based on the inclusion and exclusion criteria. Data of them were documented, and patients were followed for one year. Eventually, the association of clinical variables and RBC indices with one-year mortality was explored. RESULTS: The study included 226 (56%) men and 174 (44%) women with a median age of 66 years. Body Mass Index (HR 1.098, p = 0.016), Hb (HR 0.728, p = 0.024), HTC (HR 0.875, p = 0.066), MCHC (HR 0.795, p = 0.037), and RDW-CV (HR 1.174, p = 0.006) were confirmed as predictors of long-term mortality. Despite confirming the predictive role of these variables by ROC curves, their sensitivity and specificity were reported as follows: [72% and 50% for Hb], [75% and 52% for  HCT], [88% and 27% for MCHC], and [49% and 81% for RDW]. In addition, stratified groups of patients, based on normal cut-off values obtained from scientific literature, had significantly different survival in Kaplan-Meier analyses. CONCLUSION: Whilst proving the predictive role of Hb,  HCT, MCHC, and RDW in AHF patients, the most sensitive measurement was MCHC and the most specific one was RDW; therefore, these variables should be considered for risk stratification purposes of AHF patients in daily clinical practice.

In vitro genotoxicity assessment and 28-day repeated dose oral toxicity study of steady-calcium formula in rats.

Steady-calcium formula (SCF), a functional food mixture with potential of joint care, contains five major ingredients. However, the uncertain cross-reactivity among these included ingredients cannot be excluded. Hence, it is important to ensure the safety of this mixture. In this study, the safety of SCF was evaluated through in vitro genotoxicity assessment and 28-day oral toxicity study in rats. The bacterial reverse mutation test and mammalian chromosome aberration test displayed that SCF did not induce mutagenicity and clastogenicity. The 28-day repeated dose assessment of SCF in rats revealed no mortality and adverse effects in clinical signs, body weight, urinalysis, hematology, organ weight, and histopathology at all treated groups. Although some significant changes were observed in food intake and parameters of serum biochemistry at the highest dose in males, they were not dose-related and considered to be within normal range. These findings indicate that SCF does not possess genotoxic potential and no obvious evidence of subacute toxicity. These results demonstrate for the first time that the genotoxicity and subacute toxicity for SCF are negative under our experimental conditions and the no observed adverse effect level (NOAEL) of SCF may be defined as at least 5470 mg/kg/day.

Acute and subchronic oral toxicity assessment of extract from Etlingera pavieana rhizomes.

In Southeast Asia, the rhizome of Etlingera pavieana is commonly consumed and parts of the rhizomes have been used as a medicine for the treatment of several disorders. Its pharmacological effects have previously been reported. However, its potential toxicity has not been described. This study aimed to evaluate in vivo toxicity of E. pavieana rhizome extract (EPE) in Sprague Dawley rats. Acute toxicity testing of EPE at a single dose of 2,000 mg/kg produced no toxic effects in female rats after 14 days of treatment. Subchronic toxicity testing showed that all doses of EPE (500, 1,000, and 2,000 mg/kg/day) produced no sign of toxicity during 90 days of treatment. All biochemical and hematological values were within normal ranges. There were no significant histopathological differences in the internal organs among the tested groups. Therefore, the no-observed-adverse-effect level of EPE was 2,000 mg/kg/day in both male and female rats, thereby confirming the safety of EPE for use in traditional medicines.

Single and repeated dose (28 days) intravenous toxicity assessment of bartogenic acid (an active pentacyclic triterpenoid) isolated from Barringtonia racemosa (L.) fruits in mice.

Bartogenic acid (BA), an active pentacyclic triterpenoid, has been reported for anti-diabetic, anti-inflammatory, anti-arthritic, anti-cancer, and anti-tumor activity. However, toxicity profiling of BA has not been reported till date. Hence, this study is designed to evaluate the single dose (12.5, 25, 50 and 100 mg/kg) and repeated dose (1.5, 6, and 24 mg/kg) intravenous toxicity of BA in BALB/c mice. Control group received vehicle. In single dose toxicity study, two mortalities were observed at 100 mg/kg of BA whereas lower doses were well tolerated. In repeated dose toxicity study, no mortality was observed. 1.5 mg/kg of BA was well tolerated in mice of both sexes. At 6 mg/kg of BA, female mice showed significant reduction in the body weight as compared to the control group however no significant change was observed in male mice. 24 mg/kg of BA showed significant reduction in the body weight in mice of both sexes. Further, these mice showed significant change in the relative organ weight. However, no toxicologically relevant changes were observed in hematology, biochemistry, and histopathology. Based on the findings, No-Observed-Adverse-Effect-Level (NOAEL) for BA were found to be<24 mg/kg for male mice and<6 mg/kg for female mice.

Serum Vitamin D level and its association with red blood cell indices in patients with periodontitis.

Background: Research of late has brought to light a connect between Vitamin D and anemia. The level of 25hydroxyvitamin D (25(OH) D) is decreased in periodontitis subjects as against subjects without periodontitis and this reduced level could be related to more risk for anemia in periodontitis patients. Objective: This study aimed to evaluate the serum 25(OH) D levels and red blood cell indices in patients affected by generalized Stage III Grade B periodontitis and healthy controls and to assess the association between level of Vitamin D and red cell indices in periodontitis patients. Materials and Methods: The subjects were categorized into (i) case and (ii) control group of 30 each. Clinical parameters including oral hygiene index simplified, mean ratio of sites that bled on probing, gingival index, probing pocket depth, and the clinical attachment loss were assessed in both the groups. Subjects' blood samples (venous) were taken for the biochemical analysis. Results: In contradiction to healthy subjects, periodontitis subjects had significantly diminished 25(OH) D levels, hemoglobin (Hb), hematocrit, and mean corpuscular hemoglobin concentration (MCHC). 25(OH) D was moderately correlated with MCHC (r = 0.53) and it was statistically significant (P = 0.002). Conclusion: Periodontitis impacts Vitamin D status which further causes anemia. It suggests that effective management of periodontitis can help maintain sufficient Vitamin D status and may be vital in preventing anemia.

Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis.

Mean corpuscular hemoglobin (MCH) is a common blood routine test index. To explore the relationship between MCH and length of hospital stay in patients with acute pancreatitis (AP), we included 273 patients with AP without coronary heart disease, diabetes, hypertension and anemia in this study. All data were separated into three groups according to the length of hospital stay. Gender (p = 0.017) and severity classification (p < 0.001) were significantly correlated with length of hospital stay among three groups. Notably, MCH level was significant different among three groups (p = 0.009). Thus, all data were separated into two groups according to MCH level, and significant increases in the length of hospital stay were observed between two groups (p = 0.030). A positive correlation between length of hospital stay and MCH was observed (r = 0.172, p = 0.004). Multiple linear regression analysis showed that MCH was independent correlated with the length of hospital stay, no matter whether severity classification of AP was included (beta = 0.248, p < 0.001; beta = 0.212, p < 0.001). Our results demonstrated that the length of hospital stay was correlated with MCH level in patients with AP, and MCH level at admission may predict the length of hospital stay independent of severity classification in AP. These results may provide a potential evaluation basis for the management of patients with AP.

The Association Between Mean Corpuscular Hemoglobin Concentration and Prognosis in Patients with Acute Pulmonary Embolism: A Retrospective Cohort Study.

INTRODUCTION: Acute pulmonary embolism (APE) is a typical cardiovascular emergency worldwide. Mean hemoglobin concentration (MCHC) is a standard indicator of anemia. Studies on the association between MCHC and APE are scarce. We aimed to investigate the relationship between MCHC and APE. METHODS: Clinical data were extracted from the Medical Information Bank for Intensive Care (MIMIC)-III. Adult (≥18 years) patients with APE admitted for the first time were included in this study. An analysis was conducted to evaluate the association between MCHC and the prognosis of patients by the Cox regression analysis, generalized additives models and Kaplan-Meier survival curves. The primary outcome was 30-day mortality, and the secondary outcomes were 1-year and 3-year mortality. RESULTS: A total of 813 patients who met the selection criteria were enrolled, of whom 130 (16.0%) died within 30 days of admission. Univariate Cox regression indicated that MCHC was significantly associated with mortality (30-day: HR = 0.74, 95% CI = 0.66-0.82, P < 0.001; 1-year: HR = 0.80, 95% CI = 0.74-0.86, P < 0.001; 3-year: HR = 0.82, 95% CI = 0.77-0.88, P < 0.001). MCHC remains stable after adjusting multiple models. Kaplan-Meier survival curves showed that patients with lower MCHC had a poorer 30-day prognosis. CONCLUSIONS: Lower MCHC is an independent risk factor for increased mortality in patients with APE. As an inexpensive biomarker, MCHC should receive more attention.

Insulin Receptor Genetic Variants Causal Association with Type 2 Diabetes: A Mendelian Randomization Study.

Background: Type 2 diabetes (T2D) is a prevalent chronic disease associated with several comorbidities. Objectives: This study investigated whether the risk of T2D varied with genetically predicted insulin (INS), insulin receptor (INS-R), or insulin-like growth factor 1 receptor (IGF-1R) using genetic variants in a Mendelian randomization (MR) study. Methods: A 2-sample MR study was conducted using summary statistics from 2 genome-wide association studies (GWASs). Genetic predictors of the exposures (INS, INS-R, and IGF-1R) were obtained from a publicly available proteomics GWAS of the INTERVAL randomized controlled trial of blood donation in the United Kingdom. For T2D, the study leveraged the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) consortium. The estimated associations of INS, INS-R, and IGF-1R proteins with T2D were based on independent single nucleotide polymorphisms (SNPs) strongly (P < 5 × 10-6) predicting each exposure. These SNPs were applied to publicly available genetic associations with T2D from the DIAMANTE case (n = 74,124) and control (n = 824,006) study of people of European descent. SNP-specific Wald estimates were meta-analyzed using inverse variance weighting with multiplicative random effects. Sensitivity analysis was conducted using the weighted median (WM) and MR-Egger. Results: INS-R (based on 13 SNPs) was associated with a lower risk of T2D (OR: 0.95 per effect size; 95% CI: 0.92, 0.98; P = 0.001), with similar estimates from the WM and MR-Egger. Insulin (8 SNPs) and IGF-1R (10 SNPs) were not associated with T2D. However, 1 of the SNPs for INS-R was from the ABO blood group gene. Conclusions: This study is consistent with a causally protective association of the INS-R with T2D. INS-R in RBCs regulates glycolysis and thus may affect their functionality and integrity. However, a pleiotropic effect via the blood group ABO gene cannot be excluded. The INS-R may be a target for intervention by repurposing existing therapeutics or otherwise to reduce the risk of T2D.

Erythrocyte Indices and Hemoglobin Analysis for α-Thalassemia Screening in an Area with High Carrying Rate.

Carriers of α-thalassemia exhibit hypochromic microcytosis with mean corpuscular volume (MCV) < 80 fL, mean corpuscular hemoglobin (MCH) < 27 pg, and reduced hemoglobin A2 (HbA2). We studied the distribution and diagnostic efficiencies of these indicators and their combinations in patients with and without alpha-thalassemia. Based on genetic diagnosis, 10,883 participants were divided into alpha-thalassemia group (n = 1655) and negative-for-alpha-thalassemia group (n = 9228). Erythrocyte parameters and hemoglobin analysis of the groups were analyzed. Moreover, we compared the four screening schemes (MCV/MCH, MCV/MCH/HbA2, MCV + MCH, MCV + MCH + HbA2) to find the best for α-thalassemia screening. The genotypes of --SEA/αα, and -α3.7/αα are the most prevalent with 54.9% and 27.6% in Fujian Province, China. There were significant differences in the distribution of MCV, MCH, and HbA2 in the two groups. Among the three, MCH exhibited the highest sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. Although the four screening schemes have their advantages, there are significant differences in their sensitivity and specificity. MCV + MCH had the best diagnostic performance (72.6% sensitivity, 89.0% specificity) as well as the highest Youden index (61.59%). Our results showed that MCH could be used to screen α-thalassemia instead of MCV and HbA2. However, it is recommended that MCV/MCH/HbA2 screening be used in areas with high α-thalassemia incidence to increased sensitivity.

Evaluation of the antiparasitic activity of the chitosan-silver nanocomposites in the treatment of experimentally infested pigeons with Pseudolynchia canariensis.

This study aimed to evaluate the efficacy of chitosan-silver nanocomposites in the treatment of experimentally infested pigeons with Pseudolynchia canariensis (P. canariensis) with evaluation of different immunological parameters before and after treatment. Therefore, fourteen birds were divided into 2 groups; group1(infested group including 12 birds) which subdivided into 6 sub-groups experimentally infested pigeons 2 pigeons each, and five group of them were treated with chitosan-silver nanocomposites and sub-group number 6 was treated with deltamethrin while, group 2 including two pigeons were kept as control negative ones. P. canariensis flies distributed under the wing and /or under the tail in infested group and these pigeons showed significantly lower RBCs and higher WBCs than that in non-infested pigeons. The cell mediated immune response against experimentally infested pigeons with P. canariensis was studied. P. canariensis infestation in pigeons have a negative impact on pigeon's blood parameters, increase TNF-α and IL-1ß cytokines levels. This study cleared out the role of P. canariensis in the induction of a case of oxidative stress indicated by high level of nitric oxide and malondialdehyde (MDA) with low antioxidant capacity in shape of reduced zinc concentration in the sera of experimentally infested pigeon. Chitosan-silver nanocomposite has a promising effect in the elimination of P. canariensis infestation in pigeons.