Hemoglobin Types Research Articles

Potential of Human Hemoglobin as a Source of Bioactive Peptides: Comparative Study of Enzymatic Hydrolysis with Bovine Hemoglobin and the Production of Active Peptide α137-141.

Cruor, the main component responsible for the red color of mammalian blood, contains 90% haemoglobin, a protein considered to be a rich source of bioactive peptides. The aim of the present study is to assess the potential of human hemoglobin as a source of bioactive peptides, compared with bovine hemoglobin, which has been extensively studied in recent years. More specifically, the study focused on the α137-141 fragment of bovine haemoglobin (TSKYR), a small (653 Da) hydrophilic antimicrobial peptide. In this work, the potential of human hemoglobin to contain bioactive peptides was first investigated in silico in comparison with bovine hemoglobin-derived peptides using bioinformatics tools. The blast results showed a high identity, 88% and 85% respectively, indicating a high similarity between the α and β chains. Peptide Cutter software was used to predict cleavage sites during peptide hydrolysis, revealing major conservation in the number and location of cleavage sites between the two species, while highlighting some differences. Some peptides were conserved, notably our target peptide (TSKYR), while others were specific to each species. Secondly, the two types of hemoglobin were subjected to similar enzymatic hydrolysis conditions (23 °C, pH 3.5), which showed that the hydrolysis of human hemoglobin followed the same reaction mechanism as the hydrolysis of bovine hemoglobin, the 'zipper' mechanism. Concerning the peptide of interest, α137-141, the RP-UPLC analyses showed that its identification was not affected by the increase in the initial substrate concentration. Its production was rapid, with more than 60% of the total α137-141 peptide production achieved in just 30 min of hydrolysis, reaching peak production at 3 h. Furthermore, increasing the substrate concentration from 1% to 10% (w/v) resulted in a proportional increase in α137-141 production, with a maximum concentration reaching 687.98 ± 75.77 mg·L-1, approximately ten-fold higher than that obtained with a 1% (w/v) concentration. Finally, the results of the UPLC-MS/MS analysis revealed the identification of 217 unique peptides in bovine hemoglobin hydrolysate and 189 unique peptides in human hemoglobin hydrolysate. Of these, 57 peptides were strictly common to both species. This revealed the presence of several bioactive peptides in both cattle and humans. Although some had been known previously, new bioactive peptides were discovered in human hemoglobin, such as four antibacterial peptides (α37-46 PTTKTYFPHF, α36-45 FPTTKTYFPH, α137-141 TSKYR, and α133-141 STVLTSKYR), three opioid peptides (α137-141 TSKYR,β31-40 LVVYPWTQRF,β32-40, VVYPWTQRF), an ACE inhibitor (β129-135 KVVAGVA), an anticancer agent (β33-39 VVYPWTQ), and an antioxidant (α137-141 TSKYR). To the best of our knowledge, these peptides have never been found in human hemoglobin before.

Everything About Pulse Oximetry-Part 2: Clinical Applications, Portable/Wearable Pulse Oximeters, Remote Patient Monitoring, and Recent Advances.

Purpose: Pulse oximetry is widely used in healthcare settings for both screening and continuous monitoring. In this article, it was aimed to review some aspects of pulse oximetry including clinical applications, portable devices, and recent advances in detail. Materials and Methods: The international and national reliable sources were used in the literature review for critical data analysis. A total of 31 articles including 19 prospective comparative clinical studies, 9 reviews, 1 meta-analysis, 1 retrospective study, and 1 experimental study were used for preparation of this part of the review. Results: In this part of the article, clinical applications of pulse oximeters, portable/wearable pulse oximeters, remote patient monitoring, and recent advances were all reviewed in detail. Conclusion: Pulse oximetry is a widely used and reliable noninvasive technique that provides useful information about blood oxygenation in individuals. This technique can guide oxygen therapy, reduce the occurrence of hypoxemia, and decrease the frequency of admissions to the intensive care unit, as well as arterial blood gas sampling. New multiwaveform sensors and advanced signal processing techniques can differentiate between different types of hemoglobin and may be useful for continuous measurement of total hemoglobin, as well as for detecting and providing information on blood loss and cardiac output.

Associations between cord blood metabolic factors and early-childhood growth and overweight and obesity.

This prospective cohort study was aimed at investigating the associations between cord blood metabolic factors and early-childhood growth, further elucidating the relationships between cord blood metabolites and overweight and obesity in early life. A total of 2,267 pairs of mothers and offspring were recruited in our study. Cord blood plasma was assayed for triglycerides (TGs), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), C-peptide, insulin, and glycosylated hemoglobin type A1C (HbA1c) levels. Data of anthropometric measurements were collected from offspring at birth, 6 months, 12 months, and 18 months. Multiple linear regression models were used to evaluate the correlations between cord blood metabolic factors and weight Z-scores, body mass index (BMI) Z-scores, and weight gains at the early stage of life. Forward stepwise logistic regression analyses were applied to explore the associations between cord blood metabolic factors and early-childhood overweight and obesity. Receiver operating characteristic (ROC) curve analyses were applied to determine the optimal cutoff points for cord blood metabolic factors in predicting early-childhood overweight and obesity. After adjustments for covariates, cord blood TG concentrations and TG/TC ratios were negatively associated with weight Z-scores from birth to 18 months. Cord blood C-peptide and HbA1c levels were inversely associated with weight Z-scores at 6 months and 18 months. Cord blood TG concentrations and TG/TC ratios were negatively correlated with BMI Z-scores up to 18 months. Cord blood C-peptide levels and HbA1c levels were inversely correlated with BMI Z-scores at 18 months. Cord blood TG, TG/TC ratios, C-peptide, and HbA1c had negative correlations with weight gains from birth to 6 months, but the correlations attenuated as time went on. Increase in cord blood TG and HbA1c levels and TG/TC ratios were significantly associated with decreased risks of overweight and obesity at 6 months, 12 months, and 18 months. Cord blood metabolic factors were significantly associated with early-childhood growth patterns.

Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis.

This study aimed to evaluate the clinical efficacy and safety of 4 weekly formulations of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on glycemic control, including glycemic control, by using a network meta-analysis (NMA). PubMed, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched from inception until June 10, 2022. Randomized clinical trials (RCTs) enrolling participants with diabetes mellitus type 2 and a follow-up of at least 12 weeks were included, for which 4 eligible GLP-1RAs Exenatide, Dulaglutide, Semaglutide, Loxenatide were compared with either each other or placebo. The primary outcome is the change of hemoglobin A1c level. Secondary outcomes including additional glycemic control indicators and adverse events (AE). Frequentist random-effect NMA were conducted for effect comparison. This meta-analysis was registered on PROSPERO, CRD42022342241. The NMA synthesized evidence from 12 studies covering 6213 patients and 10 GLP-1RA regimens. A pairwise comparison of glycosylated hemoglobin type A1C (HbA1c) lowering effects showed that once-weekly GLP-1 receptor agonists were significantly better than placebo, and their glucose-lowering intensity was Semaglutide 2.0mg, Semaglutide 1.0mg, Dulaglutide 4.5mg, and Semaglutide 0.5mg, Dulaglutide 3.0mg, PEX168 200ug, Dulaglutide 1.5mg, PEX168 100ug and Dulaglutide 0.75mg. The GLP-1RA regimen has a comparable safety profile for hypoglycemia. And with the exception of PEX168, all other long-acting GLP-1RA drugs had lower rates of diarrhea, nausea and vomiting than placebo. Regimens of GLP-1RAs had differential glycemic control. The efficacy and safety of Semaglutide 2.0mg in comprehensively lowering blood sugar showed the best performance.

To study the Transfusion Practice with respect to Component Therapy in Major Obstetric Hemorrhage

Introduction: Peripartum hemorrhage is a major complicationrequiring emergency transfusion of packed blood or itscomponents with quick decision-making. We describeour experience of transfusion practices in major obstetrichemorrhage.Materials and Methods: Retrospective observational dataof all the deliveries (n = 1837) over period of one year.All cases were assessed for obstetric hemorrhage andsubsequent transfusion practices done. Demographic details,obstetric history, indications for transfusion, gestational ageat transfusion, pre- and post-transfusion hemoglobin levels,nature and type of transfusion, units of transfusion, adverseevents following transfusion and outcome in terms of morbidityand mortality were noted. Data was analyzed using SPSS 21.0software. Chi-square test was used for analysis.Results: Transfusion was required in 776 (42.2%) pregnantwomen. Obstetric hemorrhage was the indication in 432 (55.7%)of the women receiving a transfusion. Other indications wereanemia during pregnancy (39.7%) and traumatic pph (10.5%),respectively. Among major obstetric hemorrhage cases (n =432), the majority (n = 224; 51.9%) had antepartum hemorrhage(abruptio placentae/placenta previa) and the remaining 208(48.1%) had postpartum hemorrhage change no significantchange seen. A total of 138/432 (31.9%) cases had pretransfusionhemoglobin level <8 g/dl in cases of moderateanemia. PRBC was transfused to 319 (73.8%) followed byplatelets (212; 49.1%) and FFP (n = 29; 6.7%), respectively.The majority of cases required only 2 units of transfusion.There were 21 (4.9%) cases requiring more than 3 units.Post-transfusion hemoglobin levels were >10 g/dl in 319/432(73.8%) cases, thus showing a significant change (p < 0.05).Most common adverse reactions (fever/shivering) were notedin 32 (7.4%) cases. There were 6 (1.4%) mortalities (all havingpre-transfusion Hb <6 g/dl).Conclusion: The study highlighted the significance of packedblood cells and component transfusion in reducing obstetricmorbidity and mortality

P360 INFLAMMATION AND LIPID METABOLISM IN YOUNG PATIENTS WITH ACUTE CORONARY SYNDROME

Abstract Background Inflammation and lipid metabolism play a central role in pathogenesis of atherosclerosis. High sensitivity C–reactive protein (hsCRP), Lipoprotein(a) [Lp(a)] and other inflammation markers are well–established markers of cardiovascular (CV) diseases and are associated with adverse CV outcome after acute coronary syndrome (ACS). Methods The study enrolled patients ≤ 55 years of age referred to Cardiology Department of Policlinico Casilino with ACS. In order to evaluate inflammation and lipid metabolism in young patients presenting with ACS, we design an acronym to describe biochemical tests measured: ACS–Lip. Biochemical tests include: A – Apolipoprotein A (ApoA), A – Apolipoprotein B (ApoB), C – hsCRP, C – Cystatin C, S – Suppression of tumourigenicity 2 (ST2). Lip – low–density lipoprotein cholesterol (LDL), high–density lipoprotein (HDL) cholesterol and triglycerides (TG), – Lp(a), Interleukin 6 (IL–6), plasma glucose, glycosylated hemoglobin Type A1c (HbA1c) levels were also determined. Results A total of 20 patients (85% males, mean age 45.5 ± 7.7 years old) were enrolled from July 2020 to March 2022. Hs–CRP was ≥3 mg/L in 100 % of patients. Mean LDL cholesterol level at admission was 117 ± 56 mg/dL, while mean HDL cholesterol was 38 ± 11 mg/dL. Mean Lp(a) level was 42.9 ± 36.1 mg/dL. Elevated Lp(a)>30 mg/dL was documented in 55% of patients. Lp(a) level distribution in the study population is reported in Figure 1. Additional parameters are reported in Table 1. Conclusion In our experience, elevated levels of Lp(a) and of markers inflammation display a detailed profile of patients presenting with ACS at a relatively young age, identifying patients with high risk of recurrence of cardiovascular events. This result focus on the potential use in clinical practice of efficacious Lp(a)–lowering drugs and on the role on inflammatory mediators both as indicator and therapeutic target.

Influence of the sickle cell trait on Plasmodium falciparum infectivity from naturally infected gametocyte carriers

BackgroundSickle cell trait (SCT) refers to the carriage of one abnormal copy of the β-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas.MethodsThe study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source.ResultsAmong the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29–1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype.ConclusionPlasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite’s enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.

SPECTRUM OF HEMOGLOBINOPATHIES AND THALASSEMIAS DIAGNOSED ON HPLC - A TERTIARY CARE HOSPITAL BASED STUDY

Background - The most common single gene disorders in the world are hemoglobinopathies and thalassaemias. The prevalence of thalassaemias and haemoglobinopathies varies by region. However, some communities have a very high incidence due to consanguinity, caste, and area endogamy, making this group of diseases a major public health problem in our country. High performance liquid chromatography (HPLC) is an automated instrument that is highly sensitive and specic, has a high resolution, and aids in the quantication of various haemoglobins. It is a viable alternative to electrophoresis. the study comp Materials and method - rises of total 220 patients presented with anaemia and were examined in the department of Medicine. Thereafter, blood smaples were taken and the hemoglobin typing were done in the department of Pathology by Cation exchange high performance liquid chromatography. - Among the 220 cases Results majority were females with 64.1% of cases and 35.9% (79) of cases are male. Out of total cases, 119 (54.1%) cases had normal hemoglobin and 101 (45.9%) cases had variant hemoglobin. Out 101 cases of variant hemoglobin, 38 (17.3%) cases were diagnosed with Hb E trait, 27 (12.3%) cases were detected with Hb E disease, 18 (8.2%) cases were diagnosed with Hb E-β Thalassemia, 17 (7.7%) cases were diagnosed as βThalassemia trait and 1 (0.5%) case was detected as β-Thalassemia major

Effects of residential greenness and genetic predisposition on hemoglobin A1c and type 2 diabetes: Gene-environment interaction analysis from a nationwide study

BackgroundCurrent evidence on the relations of residential greenness with glucose homeostasis and type 2 diabetes (T2D) remained largely uncertain. Most importantly, no prior studies have investigated whether genetic predisposition modifies the above associations. MethodsWe leveraged data from the UK Biobank prospective cohort study, with participants enrolled between 2006 and 2010. Residential greenness was assessed by using the Normalized Difference Vegetation Index, and the weighting T2D-specific genetic risk score (GRS) was constructed based on previously published genome-wide association studies. Linear regression models and logistic regression models were used to investigate associations of residential greenness with glycated hemoglobin (HbA1c) and T2D prevalence, respectively. Interaction models explored whether genetic predisposition modifies greenness-HbA1c/T2D associations. ResultsAmong 315,146 individuals (mean [SD] age, 56.59 [8.09] years), each one-unit increase in residential greenness was associated with reduction in HbA1c (β: −0.87, 95% CI: −1.16 to −0.58) and a 12% decrease in odds of T2D (OR: 0.88, 95% CI: 0.79 to 0.98), respectively. Additionally, interaction analyses further demonstrated that residential greenness and genetic risk had cumulative effects on HbA1c and T2D. Compared with individuals who were exposed to low greenness and had high GRS, participants with low GRS and high greenness had a significant decline in HbA1c (β: −2.96, 95% CI: −3.10 to −2.82, P for interaction = 0.04) and T2D (OR: 0.47, 95% CI: 0.45 to 0.50, P for interaction = 0.09). ConclusionsWe add novel evidence that residential greenness has protective effects on glucose metabolism and T2D, and those beneficial effects can be amplified by low genetic risk. Our findings may facilitate the improvement of the living environment and the development of prevention strategies by considering genetic susceptibility to T2D.

Predicting Pain in People With Sickle Cell Disease in the Day Hospital Using the Commercial Wearable Apple Watch: Feasibility Study.

Sickle cell disease (SCD) is a genetic red blood cell disorder associated with severe complications including chronic anemia, stroke, and vaso-occlusive crises (VOCs). VOCs are unpredictable, difficult to treat, and the leading cause of hospitalization. Recent efforts have focused on the use of mobile health technology to develop algorithms to predict pain in people with sickle cell disease. Combining the data collection abilities of a consumer wearable, such as the Apple Watch, and machine learning techniques may help us better understand the pain experience and find trends to predict pain from VOCs. The aim of this study is to (1) determine the feasibility of using the Apple Watch to predict the pain scores in people with sickle cell disease admitted to the Duke University SCD Day Hospital, referred to as the Day Hospital, and (2) build and evaluate machine learning algorithms to predict the pain scores of VOCs with the Apple Watch. Following approval of the institutional review board, patients with sickle cell disease, older than 18 years, and admitted to Day Hospital for a VOC between July 2021 and September 2021 were approached to participate in the study. Participants were provided with an Apple Watch Series 3, which is to be worn for the duration of their visit. Data collected from the Apple Watch included heart rate, heart rate variability (calculated), and calories. Pain scores and vital signs were collected from the electronic medical record. Data were analyzed using 3 different machine learning models: multinomial logistic regression, gradient boosting, and random forest, and 2 null models, to assess the accuracy of pain scores. The evaluation metrics considered were accuracy (F1-score), area under the receiving operating characteristic curve, and root-mean-square error (RMSE). We enrolled 20 patients with sickle cell disease, all of whom identified as Black or African American and consisted of 12 (60%) females and 8 (40%) males. There were 14 individuals diagnosed with hemoglobin type SS (70%). The median age of the population was 35.5 (IQR 30-41) years. The median time each individual spent wearing the Apple Watch was 2 hours and 17 minutes and a total of 15,683 data points were collected across the population. All models outperformed the null models, and the best-performing model was the random forest model, which was able to predict the pain scores with an accuracy of 84.5%, and a RMSE of 0.84. The strong performance of the model in all metrics validates feasibility and the ability to use data collected from a noninvasive device, the Apple Watch, to predict the pain scores during VOCs. It is a novel and feasible approach and presents a low-cost method that could benefit clinicians and individuals with sickle cell disease in the treatment of VOCs.

Are IL-1 family cytokines important in management of sickle cell disease in Sub-Saharan Africa patients?

Sickle cell disease (SCD) is the most common genetic disease found in Africa and throughout the world. It is responsible for a high rate of hemolysis, systemic inflammation, and modulation of the immune system with the involvement of immunological molecules, such as cytokines. IL-1β is a major inflammatory cytokine. IL-18 and IL-33, members of IL-1 family, also exhibit characteristics of inflammation-related cytokines. Thus, in order to contribute to the evaluation of the severity and prognosis of SCD in Africa, this study aimed to estimate the cytokine response, in particular the levels of cytokines of the IL-1 family, in sickle cell patients living in a Sub-Saharan country. Ninety patients with a diagnosis of SCD were recruited with different hemoglobin types. Samples were assessed for cytokine levels using the Human Inflammation Panel assay from BioLegend. The assay allows the simultaneous quantification of 13 human inflammatory cytokines/chemokines, i.e., IL-1β, IFN-α2, IFN-γ, TNFα, MCP-1 (CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33. the assessment of plasma cytokines in SCD patients revealed significantly increased levels of IL-1 family cytokines in crisis compared to steady state, suggesting a substantial involvement of these cytokines in clinical exacerbation. This suggests the possibility of a causal effect in the SCD pathology and can open the way to define better care, pointing toward new therapeutic avenues for sickle disease in Sub-Saharan Africa.

Prevalence of Hemoglobinopathies in Premarital Screening in the Province of Nigde, Turkey

Hemoglobinopathies are one of the most widespread hereditary disorders in Turkey. The present study aimed to determine the prevalence of hemoglobinopathies in the Nigde province of Turkey. This study was conducted with 2013 individuals who applied for the premarital screening, between January 2019 and December 2021. The complete blood count was measured by an automated hematology analyzer. The types of hemoglobin were determined by high-performance liquid chromatography. A total of 2013 individuals including 951 (47.2%) females and 1062 (52.8%) males, were screened within the premarital screening program, and 67 (3.3%) of them were migrants. 53 out of 2013 (2.63%) individuals were identified as β thalassemia carriers, and five of them were migrants including two from Afghanistan, two from Iran, and one from Georgia. HbC was observed in two cases, a couple from Syria (0.1%), HbD in two cases (0.1%), HbE in one case from Thailand (0.05%), HbS-β-thalassemia in one case (0.05%), delta-β thalassemia in one case (0.05%), and unidentified structural variant in one case (0.05%). Moreover, 183 individuals (9.1%) were considered to have iron deficiency, α-thalassemia, or silent β-thalassemia carrier. These results indicate that the province of Nigde is a relatively risky region regarding hemoglobinopathies. Geographic location and immigrant population may have slightly affected the local prevalence of hemoglobinopathies and could be taken into consideration to ensure the effective implementation of the hemoglobinopathy prevention program.

An Acromegalic Patient with Sickle Cell Disease Undergoing Endoscopic Trans-Sphenoidal Surgery: Anesthetic Concerns for a Neuroanesthesiologist

AbstractSickle cell disease (SCD) refers to a group of hemoglobinopathies that include mutations in the gene encoding the β subunit of hemoglobin. The glutamine in the heme portion of the hemoglobin molecule is abnormally substituted by valine. Sickle hemoglobin (hemoglobin type S), when gets deoxygenated, tends to polymerize and aggregate leading to vaso-occlusion and organ ischemia. Such patients are at increased risk of perioperative mortality and severe complications like vaso-occlusive crisis, acute chest syndrome, and congestive heart failure. We describe the perioperative management of a case of SCD with acromegaly scheduled for trans-sphenoidal removal of a functional pituitary adenoma. The acromegalic habitus, the cardiovascular effects of acromegaly, and the hormonal imbalances due to pituitary adenoma pose challenges in addition to the challenge of preventing complications of SCD making the anesthetic management more exigent.

Pulmonary Hypertension in a Group of Patients with Various Stages of Renal Disease

Background: The pathogenesis of pulmonary hypertension (PHT) associated with renal failure is complex. It includes metabolic and hormonal changes, high cardiac output due to arteriovenous fistula (AVF), anemia, and other factors. Objectives: The objective is to identify PHT frequency and associated factors in patients on hemodialysis (HD) compared to patients, not on HD. Methods: A cross-sectional study was conducted at Ibn Sena teaching hospital/Mosul and included 100 diabetic males with end-stage renal disease on HD (Group 1) compared to 96 diabetic males (of similar age) with chronic kidney disease but not on HD (Group 2) to assess the pulmonary artery pressure using Doppler echocardiogram. Patients with other causes of PHT such as heart failure and chronic lung disease were excluded from the study. Results: 42 (42%) of patients in Group 1 had PHT and 12 (12.5%) patients in Group 2. There were statistically significant differences between patients with and without PHT regarding ejection fraction (EF), but no significant differences regarding age, duration of dialysis, hemoglobin (Hb), and vascular access type in both groups. Conclusions: EF had a relationship with PHT, whereas the duration of dialysis, age of patients, Hb, and dialysis access type had no relationship to PHT. Recommendations: More studies are needed in our country regarding PHT in patients with variable stages of renal disease with larger sample sizes and different designs with the inclusion of data and parameters that were missing in our study such as duration of AVF creation.

Interferência do ferro na produção de hemoglobina de leitões do nascimento a desmama

ABSTRACT: Iron deficiency anemia (IDA) in humans is defined as the decrease of total hemoglobin concentration and the non-production of the adult hemoglobin subtype 2 - HbA2 (α2δ2 chains), which is considered a marker of IDA severity in humans, dosed together with the iron serum. This study aimed to determine the standard of hemoglobin types in piglets induced to experimentally IDA in the first 21 days of life (delivery to weaning). In the present study, 40 piglets born from four naïve gilts, were randomly and equally assigned among the gilts. On the third day after delivery, the groups were randomly distributed in different environments (cement and clay floors) and according to the iron supplementation (iron dextran and placebo). Erythrocyte parameters, serum iron, and hemoglobin trait were analyzed at four moments between birth and weaning days. The group of piglets that did not receive iron dextran supplementation on the third-day post-birth and were placed in the pen without soil did not present HbA2 from the seventh day onwards on the agarose electrophoretogram (pH 8.6) and this observation was correlated to decrease of serum iron (ρ: 0.156, p=0.003) when compared to the other groups’ piglets that did not present iron deficiency. In the present study was possible to determine the swine hemoglobin pattern in IDA, since HbA2 was absent in piglets with IDA in comparison to the non-ferropenic groups and the correlation between the reduction of iron levels and the absence of HbA2.

Comparative Analysis of Different Prognostic Markers in Predicting Outcome in Advanced Heart Failure

Introduction: Heart failure (HF) is a debilitating condition with an adverse outcome, especially during the advanced stage having higher morbidity and mortality rates. Various parameters have been used as prognostic markers in advanced HF. This study highlights about the comparative analysis of different prognostic markers in predicting mortality in advanced HF. Methods: This prospective observational study was conducted in patients of advanced HF admitted to the department of medicine intensive care unit in a rural tertiary care hospital from 2018 to 2020. Advanced HF was diagnosed using the updated HF Association-European Society of Cardiology criteria. The serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), six-minute walk test (6MWT), left ventricular ejection fraction (LVEF), estimated glomerular filtration rate, and glycosylated hemoglobin type A1c levels were measured on admission. Receiver operating characteristic (ROC) curve was also studied for the above-mentioned variables, and the area under ROC curve (AUROC) was also determined. Results: Seventy-five patients with an average age of 60.55 ± 14.04 years were evaluated. Out of 75, 48 (64%) were male and 27 (36%) were female. There was inhospital mortality in 20 (26.67%) patients. The mean NT-proBNP levels among the mortality group was 9826.95 ± 3485.10 pg/mL, while in nonmortality group, it was 6135.40 ± 2342.77 pg/mL (P = 0.001). The cutoff range in this study for on-admission serum NT-proBNP levels was 8990 pg/mL, with AUROC of 0.81, the sensitivity of 70.0%, and specificity of 90.9%. In multiple regression analysis keeping mortality as the dependent variable, it was seen that variables NT-proBNP, 6MWT (<300 m), and LVEF were significantly associated with mortality. Conclusion: Serum NT-proBNP and 6MWT (<300 m) were important predictors of mortality in advanced HF.

A retrospective cohort study on the use of machine learning to predict stone-free status following percutaneous nephrolithotomy: An experience from Saudi Arabia.

Machine learning techniques have been used extensively in the field of clinical medicine, especially when used for the construction of prediction models. The aim of the study was to use machine learning to predict the stone-free status after percutaneous nephrolithotomy (PCNL). This is a retrospective cohort study of 137 patients. Data from adult patients who underwent PCNL at our institute were used for the purpose of this study. Three supervised machine learning algorithms were employed: Logistic Regression, XGBoost Regressor, and Random Forests. A set of variables comprising independent attributes including age, gender, body mass index (BMI), chronic kidney disease (CKD), hypertension (HTN), diabetes mellitus, gout, renal and stone factors (previous surgery, stone location, size, and staghorn status), and pre-operative surgical factors (infections, stent, hemoglobin, creatinine, and bacteriuria) were entered. 137 patients were identified. The majority were males (65.4%; n=89), aged 50 years and above (41.9%; n=57). The stone-free status (SFS) rate was 86% (n=118). An inverse relation was detected between SFS, and CKD and HTN. The accuracies were 71.4%, 74.5% and 75% using Logistic Regression, XGBoost, and Random Forest algorithms, respectively. Stone size, pre-operative hemoglobin, pre-operative creatinine, and stone type were the most important factors in predicting the SFS following PCNL. The Random Forest model showed the highest efficacy in predicting SFS. We developed an effective machine learning model to assist physicians and other healthcare professionals in selecting patients with renal stones who are most likely to have successful PCNL treatment based on their demographics and stone characteristics. Larger multicenter studies are needed to develop more powerful algorithms, such as deep learning and other AI subsets.

Associations between type of blood collection, analytical approach, mean haemoglobin and anaemia prevalence in population-based surveys: A systematic review and meta-analysis.

Previous studies have observed that haemoglobin concentrations can be affected by type of blood collection, analysis methods and device, and that near-in-time population-based surveys report substantially different anaemia prevalence. We investigated whether differences in mean haemoglobin or prevalence of anaemia between near-in-time surveys of the same population were associated with differences in type of blood collection or analytic approach to haemoglobin measurement. We systematically identified pairs of population-based surveys that measured haemoglobin in the same population of women of reproductive age (WRA) or preschool-aged children (PSC). Surveys were matched on geographic coverage, urban/rural place of residence, inclusion of pregnant women, time of data collection (within 18 months), and, to the extent feasible, age range. Differences in anaemia prevalence were presented graphically. Random-effects meta-analysis and meta-regression of difference in mean haemoglobin were carried out, with subgroups defined by comparison of type of blood collection and analytic approach within each survey pair. We included 23 survey pairs from 17 countries for PSC and 17 survey pairs from 11 countries for WRA. Meta-regression indicates that surveys measuring haemoglobin with HemoCue® Hb 301 found higher haemoglobin concentrations than near-in-time surveys using HemoCue® Hb 201+ in non-pregnant women ((NPW); 5.8 g/L (95% confidence interval (CI) = 3.2-8.3) mean difference, n = 5 pairs) and PSC (4.3 g/L (1.4-7.2), n = 6). Surveys collecting venous blood found higher haemoglobin concentrations than near-in-time surveys collecting capillary blood in PSC (3.8 g/L (0.8-6.7), n = 8), but not NPW (0.4 g/L (-1.9-2.8), n = 9). Because this study is observational, differences in haemoglobin concentrations in near-in-time surveys may be caused by other factors associated with choice of analytic approach or type of blood collected. The source or sources of differences should be clarified to improve use of surveys to prioritize and evaluate public health programs. PROSPERO CRD42022296553.

Stability of Hemoglobin Constant Spring Identified by Capillary Electrophoresis.

Hemoglobin Constant Spring (HbCS) is often missed by routine hemoglobin analysis. The aim of this research was to study HbCS stability as identified by capillary electrophoresis (CE) to determine the specimen storage time limit. The EDTA blood of 29 HbCS samples were kept at 4°C and analyzed every workday until CE could not detect HbCS or until 7 weeks after blood collection. The genotypes were confirmed by multiplex polymerase chain reaction. The median subject age was 27 years and 10 subjects were male. The HbCS levels were stable during the first 7 days but became undetectable in 5 cases (17.2%) after 1 week. All of them were heterozygous HbCS. Longer detection times were correlated with the higher baseline HbCS levels, with a correlation coefficient of 0.582 (P ≤ 0.001). Routine hemoglobin typing and quantitation should be performed within 1 week after blood collection to detect low HbCS levels, especially in heterozygous HbCS.

EVOLUTIONARY HISTORY OF THE APEX1 GENE: FROM VERTEBRATES TO SICKLE CELL ANEMIA

In sickle cell anemia, it is known that the APEX1 gene, which encodes the APE1 protein, plays several roles, including DNA strand repair and redox functions, and it is highly expressed during the inflammatory process. The present study sought to investigate how conserved the APEX1 gene is in vertebrates. For this, the coding sequences of the APEX1 gene were obtained by searching genomic databases at the NCBI, with 14 sequences ( Pan troglodytes, Macaca mulatta, Homo sapiens, Bos taurus, Cervos elaphaus, Gallus gallus, Lagopus muta, Petromyson marinus, Felis catus, Rattus norvengicus, Alosa alosa, Dermochelys coriacea, Caretta caretta, Trachemys scriptaelegans) being chosen, using up to 300 amino acids as a selection criterion. After the sequences of the species were aligned using MAFFT v7.407 software, the quality of the sequences was verified and the aligned regions without divergence information were removed using Gblocks. Following this, phylogenetic trees were constructed using the MEGA-X software using the Maximum Likelihood method with 1,000 bootstraps. The generated phylogenies were edited using the FigTree version 1.44 program. A similarity in gene conservation has been observed in Primate species ( Pan troglodytes, Macaca mulatta , and Homo sapiens ). There was a grouping in the same clade of the species, Bos taurus and Cervus elaphus ; the same happened with the order Galliforme ( Gallus gallus and Lagopus muta ) and among the studied reptile species. The vertebrate that presented the least evolutionarily conserved gene was the marine lamprey ( Petromyson marinus) . According to the findings, APEX1 is linked to the oxidative stress pathway in diseases such as sickle cell anemia, preventing further oxidative damage and regulating transcription factors involved in the redox process. Interesting to note is the existence of sicklings of erythrocytes in deer; however, the genetic basis of the phenomenon is still unknown. It is, however, evident that sickling and the APEX1 gene may be related in an adaptive manner. There was a genetic distance of seventy for the APEX1 gene in Felis catus , which suggests that the presence of sickle erythrocytes is not related to the type of hemoglobin since feline hemoglobin contains six additional sulfhydryl groups compared to human hemoglobin. As for reptiles, grouped into a single clade, it is known that they may have sickled erythrocytes, however, unlike Primates, these are nucleated. Unlike the other groups, the capillary diameter in reptiles is greater, which in turn could favor a decrease in vaso-occlusive processes. The inflammatory process in vertebrates is accompanied by a series of cellular and molecular mechanisms that can trigger different costs, which are optimized by the forces of natural selection. The sickling of erythrocytes, which can culminate in inflammatory events, is common in some groups of the animal kingdom. It increases the expression of the APEX1 gene, which has been shown to be evolutionarily more conserved in animals with similar erythrocyte sickling mechanisms, suggesting that it has evolved convergently to protect against oxidative stress.