Causal relationship between varicose veins and mean corpuscular hemoglobin concentration based on Mendelian randomization study.

BACKGROUND: Increased hemoglobin concentrations may increase the risk of varicose veins. However, the underlying relationship between them was not yet understood. METHODS: Mendelian randomization (MR) analysis was performed to investigate causal effect between mean corpuscular hemoglobin concentration (MCHC, exposure factor) and varicose veins (outcome). Afterward, sensitivity analysis was used to ensure the reliability of MR analysis results. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of SNPs were performed. A search tool for recurring instances of neighbouring genes (STRING) database was used to construct a protein-protein interaction (PPI) network. RESULTS: Therefore, the inverse-variance weighted (IVW) results showed there existed a causal relationship between MCHC and varicose veins (p = 0.0026), with MCHC serving as a significant risk factor. (odd ratio [OR] = 1.2321). In addition, the validity of the results of the forward MR analysis was verified by sensitivity analysis. Further, a PPI network of 92 single-nucleotide polymorphisms (SNPs) which used for forward MR analysis related genes was constructed. And they were found to be closely associated with the peroxisome proliferator-activated receptor (PPAR) signalling pathway and cellular response to external stimulus by enrichment analysis. In addition, we clarified that the effect of varicose veins on MCHC was minimal by reverse MR analysis, suggesting that the results of forward MR analysis were not disturbed by reverse results. CONCLUSION: This study found a causal relationship between varicose veins and MCHC, which provided strong evidence for the effect of hemoglobin on varicose veins, and a new thought for the diagnosis and prevention of varicose veins in the future.

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.

Folate Forms in RBC and Whole-Blood Lysates Appear Stable When Stored Frozen for 2 Years.

BACKGROUND: The use of RBC lysate (RBC-Lys) eliminates the need for serum folate and hematocrit (Hct) measurement to calculate RBC folate. Information on the long-term frozen storage stability of RBC-Lys is missing. OBJECTIVES: We aimed to assess the comparability of RBC folate forms in whole-blood lysate (WB-Lys) and RBC-Lys and the folate stability in both matrices. METHODS: We prepared conventional WB-Lys (1:11 dilution with 1% ascorbic acid) and RBC-Lys (1:11 dilution of washed and saline-diluted RBCs with 1% ascorbic acid) from EDTA blood (n = 60 adult donors) and stored lysates at -70°C until analysis at baseline (1 wk), 3, 6, 12, and 24 mo. Before analysis by HPLC-tandem MS, we incubated the WB-Lys (4 h at 37°C) and treated the RBC-Lys with human recombinant γ-glutamyl hydrolase for folate polyglutamate deconjugation. We analyzed RBC-Lys samples for hemoglobin (Hb) (same aliquot) to normalize for the preanalytical dilution; Hb-folate was converted to RBC folate for each folate form using the mean corpuscular Hb concentration. We analyzed Hct as well as folate forms in matching serum samples for traditional RBC folate calculation. We conducted descriptive data analyses (correlation, Bland-Altman plot, Deming regression). RESULTS: At baseline, results for RBC folate forms derived from WB-Lys compared with RBC-Lys samples showed excellent correlation (Pearson r ≥ 0.97). Mean ± SD concentrations compared well for total folate (WB-Lys: 886 ± 255 compared with RBC-Lys: 899 ± 271 nmol/L), 5-methyltetrahydrofolate (WB-Lys: 831 ± 258 compared with RBC-Lys: 843 ± 276 nmol/L), and nonmethyl folate (WB-Lys: 53.3 ± 74.4 compared with RBC-Lys: 52.9 ± 70.7 nmol/L), but were 17% higher in RBC-Lys for pyrazino-s-triazine derivative of 4α-hydroxy-5-CH3-H4folate (MeFox) (WB-Lys: 147 ± 44.1 compared with RBC-Lys: 172 ± 53.5 nmol/L). Frozen storage of WB-Lys and RBC-Lys samples for ≤24 mo showed ≤5%, ≤5%, ≤13%, and ≤11% change in total folate, 5-methyltetrahydrofolate, nonmethyl folate, and MeFox, respectively. CONCLUSIONS: Erythrocyte folate forms appear to be stable in RBC-Lys samples stored frozen at -70°C for ≤2 y. The relatively small changes in folate concentrations over time were comparable between RBC-Lys and conventionally prepared WB-Lys samples.

Pre-clinical safety evaluation of the synthetic human milk, nature-identical, oligosaccharide 2'-O-Fucosyllactose (2'FL).

In order to match the composition of human breast milk more closely, it is now possible to supplement commercial infant formula (IF) with synthesised oligosaccharides that are chemically identical to human milk oligosaccharides. The safety data generated on a new human-identical milk oligosaccharide (HiMO), 2'-O-Fucosyllactose (2'FL), are presented. Standard in vitro genotoxicity tests were performed. To investigate the toxicological profile in a model representative of the intended target population, 2'FL was administered via gavage in a juvenile adapted sub-chronic rat study at dose levels of 0, 2000, 5000 and 6000 mg/kgbw/day. Fructooligosaccharide (FOS), currently acknowledged as safe and approved for use in IF, was used as a reference high-dose control at 6000 mg/kgbw/day. 2'FL was non-mutagenic in the in vitro assays. Oral administration up to 5000 mg/kgbw/day to rats over 90 days was not associated with any adverse effects based on clinical observations, body weight gain, food consumption, ophthalmoscopy, clinical pathology, organ weights and histopathology findings. Based on this 90-day study, a No Observed Adverse Effect Level (NOAEL) of 5000 mg/kgbw/day for both male and female rats was established for 2'FL. These findings support the safety of synthetic 2'FL for possible use in infant food.

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.

Risk of low levels of blood group antibodies mediating hemolysis in ABO-incompatible neonates with negative three hemolysis tests.

Objective: To explore the risk of low-level blood group antibody-mediated hemolysis in ABO-incompatible newborns with negative three hemolysis tests, aiming to assist in the identification and management of neonatal jaundice. Methods: A retrospective case-control study was performed in 892 children with jaundice. The patients were divided into three groups: group I, ABO compatible, negative three hemolysis tests; group II, ABO incompatible, negative three hemolysis tests; and group III, ABO incompatible, positive three hemolysis tests. We analyzed the differences in clinical data, blood routine and biochemical laboratory results. Results: (1) Patients in group II had higher levels of mean corpuscular volume (MCV), standard deviation of red blood cell volume distribution width (RDW-SD), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and bile acid (BA) than those in group I (P < 0.05). However, there were no statistically significant differences in the MCV, ALT, ALP and BA levels between groups II and III (P > 0.05). (2) Mean corpuscular hemoglobin concentration (MCHC) >359.5 g/L, cell volume distribution width (RDW-CV) >15.95%, and reticulocyte count (RET) >4.235% were identified as independent predictors of positive hemolysis test results (P < 0.001). The combination of MCHC, RDW-CV, and RET% yielded an AUC of 0.841. Conclusion: Low-level blood group antibody-mediated hemolysis may occur in ABO-incompatible neonates even when three hemolysis tests are negative. Changes in liver function parameters must be monitored. The combination of MCHC, RDW-CV, and RET% can be used to improve the detection rate of HDN.

Hematocrit and oxygenation dependence of blood (1)H(2)O T(1) at 7 Tesla.

Knowledge of blood (1)H2O T1 is critical for perfusion-based quantification experiments such as arterial spin labeling and cerebral blood volume-weighted MRI using vascular space occupancy. The dependence of blood (1)H2O T1 on hematocrit fraction (Hct) and oxygen saturation fraction (Y) was determined at 7 T using in vitro bovine blood in a circulating system under physiological conditions. Blood (1)H2O R1 values for different conditions could be readily fitted using a two-compartment (erythrocyte and plasma) model, which are described by a monoexponential longitudinal relaxation rate constant dependence. It was found that T1 = 2171 ± 39 ms for Y = 1 (arterial blood) and 2010 ± 41 ms for Y = 0.6 (venous blood), for a typical Hct of 0.42. The blood (1)H2O T1 values in the normal physiological range (Hct from 0.35 to 0.45, and Y from 0.6 to 1.0) were determined to range from 1900 to 2300 ms. The influence of oxygen partial pressure (pO2) and the effect of plasma osmolality for different anticoagulants were also investigated. It is discussed why blood (1)H2O T1 values measured in vivo for human blood may be about 10-20% larger than found in vitro for bovine blood at the same field strength.

Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague-Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expression of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 µg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ~30-45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species.

Assessment of DNA damage and lipid peroxidation in diabetic mice: effects of propolis and epigallocatechin gallate (EGCG).

There is growing recognition that polyphenolic compounds present in many plants and natural products may have beneficial effects on human health. Propolis - a substance produced by honeybees - and catechins in tea, in particular (-)-epigallocatechin gallate (EGCG), are strong antioxidants that appear to have anti-obesity and anti-diabetic effects. The present study was designed to elucidate the anti-diabetic effect of the water-soluble derivative of propolis (WSDP), which contains phenolic acids as the main compounds, and EGCG in alloxan-induced (75mg/kg, iv) diabetes in mice. Intraperitoneal administration of EGCG or propolis at doses of 50mg/kg body weight (bw) to diabetic mice for a period of 7 days resulted in a significant increase in body weight and in haematological/immunological blood parameters, as well as in 100% survival of the mice. A significant decrease in lipid peroxidation in liver, kidney and brain tissue was also observed in diabetic mice treated with these two agents. Additionally, EGCG and propolis clearly reduced DNA damage in peripheral lymphocytes of diabetic mice. Our studies demonstrate the anti-oxidative and anti-inflammatory potential of WSDP and EGCG, which could exert beneficial effects against diabetes and the associated consequences of free-radical formation in kidney, liver, spleen and brain tissue. The results suggest that dietary supplementation with WSDP or EGCG could potentially contribute to nutritional strategies for the prevention and treatment of diabetes mellitus.

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.

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.

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.

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.

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.

Higher Mean Corpuscular Hemoglobin Concentration is Associated with Worse Prognosis of Hepatorenal Syndrome: A Multicenter Retrospective Study.

BACKGROUND: Hepatorenal syndrome (HRS) is a severe complication of decompensated cirrhosis with high mortality. However, few prognostic factors have been identified and studies are urgently needed to facilitate precise treatment. METHODS: Patients with decompensated cirrhosis and acute kidney injury were enrolled from four general hospitals between January 2010 and March 2020. Demographic and laboratory data were compared between surviving and non-surviving patients and also among different levels of HRS severity. COX regression analysis was performed to determine the effect of mean corpuscular hemoglobin concentration (MCHC) on survival of patients with HRS. RESULTS: Out of a total of 1287 patients enrolled, 325 patients were analyzed. MCHC was significantly higher in non-survivors than in survivors, and in patients with more serious disease, defined as failure of organ systems. The hazard ratio (HR) of mortality was 1.17, 1.18 and 1.11, when adjusted by the crude model, model 1 and model 2, respectively. When MCHC was converted to a categorical variable based on the quartile of MCHC, the HR for the highest quartile of MCHC was 2.11 (95% CI: 1.45-3.06, P <0.05) compared to the lowest quartile of MCHC in the crude model, and when adjusted for age and sex (model 1), the HR was 2.20 (95% CI: 1.52-3.20, P <0.05). In model 2, which was adjusted for complex characteristics, the HR was 1.77 (95% CI: 1.17-2.68, P <0.05). The results of Kaplan-Meier curves were consistent with those from Cox regression analysis. CONCLUSIONS: Higher MCHC was associated with worse prognosis in HRS.

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.

Associations between differences in anemia-related blood cell parameters and short-term exposure to ambient particle pollutants in middle-aged and elderly residents in Beijing, China.

Anemia is a highly prevalent disease among older populations, with multiple adverse health outcomes, and particles exposure is a potential risk factor for anemia. However, evidence on associations of exposure to particles with small size with anemia-related blood cell parameters levels in the elderly is limited, and the underlying mechanisms are unclear. Based on a panel study in Beijing, we found that in 135 elderly participants, mass concentrations of particle with an aerodynamic diameter ≤ 2.5 µm (PM2.5), black/elemental carbon (BC/EC, particle size range: 0-2.5 µm), and number concentrations of ultrafine particles (UFPs, particle size range: 5.6-93.1 nm) and accumulated mode particles (Acc, size range: 93.1-560 nm) were significantly associated with levels of red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC). The mean ± SD for PM2.5, UFPs, Acc, BC, OC, and EC were 69.7 ± 61.1 µg/m3, 12.5 ± 4.3 × 103/cm3, 1.6 ± 1.2 × 103/cm3, 3.0 ± 2.0 µg/m3, 8.7 ± 6.7 µg/m3, and 2.1 ± 1.6 µg/m3, respectively. Cotinine (higher than 50 ng/mL) is used as an indicator of smoking exposure. The association between MCHC difference and per interquartile range (IQR) increase in average UFPs concentration 14 d before clinical visits was -0.7% (95% CI: -1.1% to -0.3%). Significant associations of UFPs and Acc exposure with MCHC and MCH levels remain robust after adjustment for other pollutants. Furthermore, 25.2% (95% CI: 7.4% to 64.8%) and 29.8% (95% CI: 5.3% to 214.4%) of the difference in MCHC associated with average UFPs and Acc concentrations 14 d before clinical visits were mediated by the level of tumor necrosis factor α (TNF α), a biomarker of systemic inflammation. Our findings for the first time provide the evidence that short-term UFPs and Acc exposure contributed to the damage of anemia-related blood cell in the elderly, and systemic inflammation was a potential internal mediator.

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.

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.