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Background: Thalassemia is a inherited monogenic blood disorder and more prevalent in southern China. In this study, Our aim was to elucidate the molecular spectrum and phenotypic features of thalassemia in pregnant women in Changsha County. Methods: Next-generation sequencing (NGS) was conducted for 38,810 pregnant women to diagnose thalassemia in Changsha County. Further analysis of hematological parameters was conducted on subjects who had not previously undergone thalassemia screening in other hospitals. Results: In this study, 2,208 (5.69%) pregnant women were diagnosed as carriers of thalassemia using NGS analysis. Among 1,594 cases of α-thalassemia, 23 genotypes were identified, and among 578 cases of β-thalassemia, 22 genotypes were detected. Additionally, 18 genotypes were detected among 36 cases of composite α- and β-thalassemia. Among all carriers of thalassemia, 8 rare α-mutations and 11 rare β-mutations were found in the study population. Notably, pregnant women diagnosed as carriers of thalassemia tended to have lower hemoglobin levels. Furthermore, multivariable logistic regression analysis indicates that the values of MCV and MCH have the greatest impact on genetic diagnosis. Conclusion: Our study has provided detailed genotypes and hematological parameters of thalassemia in pregnant women in Changsha county and reveal that certain abnormal blood parameters have a remarkably impact on genetic diagnosis results. Furthermore, our data suggest that combining hemoglobin electrophoresis and NGS provides a powerful tool for prenatal diagnosis, which will increase the accuracy of clinical diagnosis of thalassemia. [ABSTRACT FROM AUTHOR]

The factor V Leiden (FVL) polymorphism is known as the most common inherited risk factor for venous thrombosis. In turn, FVL is the leading cause of an activated protein C resistance (APCR) phenotype, in which the addition of exogenous activated protein C to plasma does not result in the expected anticoagulant effect. In the routine laboratory approach to the formal diagnosis of FVL, an initial positive screening plasma-based method for APCR is often performed, and only if needed, this is followed by a confirmatory DNA-based assay for FVL. Multiple methods with accepted sensitivity and specificity for determining an APCR/FVL phenotype are commonly categorized into two separate groups: (1) screening plasma-based assays, including qualitative functional clot-based assays, for APCR, and (2) confirmatory DNA-based molecular assays, entailing several tests and platforms, including polymerase chain reaction-based and non-PCR-based techniques, for FVL. This review will describe the methodological aspects of each laboratory test and prepare suggestions on the indication of APCR and FVL testing and method selection. [ABSTRACT FROM AUTHOR]

Background: As an important downstream effector of various signaling pathways, mTOR plays critical roles in regulating many physiological processes including erythropoiesis. It is composed of two distinct complexes, mTORC1 and mTORC2, which differ in their components and downstream signaling effects. Our previous study revealed that the inhibition of mTORC1 by rapamycin significantly repressed the erythroid progenitor expansion in the early stage but promoted enucleation and mitochondria clearance in the late stage of erythroid differentiation. However, the particular roles and differences of mTORC1 and mTORC2 in the regulation of erythropoiesis still remain largely unknown. In the present study, we investigated the comparative effects of dual mTORC1/mTORC2 mTOR kinase inhibitor AZD8055 and mTORC1 inhibitor rapamycin on erythroid differentiation in K562 cells induced by hemin and erythropoiesis in β‐thalassemia mouse model. Materials and Methods: In vitro erythroid differentiation model of hemin‐induced K562 cells and β‐thalassemia mouse model were treated with AZD8055 and rapamycin. Cell Counting Kit‐8 was used to detect cell viability. The cell proliferation, cell cycle, erythroid surface marker expression, mitochondrial content, and membrane potential were determined and analyzed by flow cytometry and laser scanning confocal microscopy. Globin gene expression during erythroid differentiation was measured by RT‐qPCR. The mTORC2/mTORC1 and autophagy pathway was evaluated using western blotting. Results: Both AZD8055 and rapamycin treatments increased the expression levels of the erythroid differentiation‐specific markers, CD235a, α‐globin, γ‐globin, and ε‐globin. Notably, AZD8055 suppressed the cell proliferation and promoted the mitochondrial clearance of hemin‐induced K562 cells more effectively than rapamycin. In a mouse model of β‐thalassemia, both rapamycin and AZD8055 remarkably improve erythroid cell maturation and anemia. Moreover, AZD8055 and rapamycin treatment inhibited the mTORC1 pathway and enhanced autophagy, whereas AZD8055 enhanced autophagy more effectively than rapamycin. Indeed, AZD8055 treatment inhibited both mTORC2 and mTORC1 pathway in hemin‐induced K562 cells. Conclusion: AZD8055 is more effective than rapamycin in inhibiting proliferation and promoting mitochondrial clearance in erythroid differentiation, which might provide us one more therapeutic option other than rapamycin for ineffective erythropoiesis treatment in the future. These findings also provide some preliminary information indicating the roles of mTORC1 and mTORC2 in erythropoiesis, and further studies are necessary to dissect the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop and assess a novel reverse dot blot assay for the simultaneous detection of 10 types of α-thalassemia alleles in the Chinese population, including six common variants of-SEA, -α3.7, -α4.2, αCS, αQS, and αWS, and four rare variants of αααanti-4.2, αααanti-3.7, --FIL deletion and--THAI deletion. Methods: The novel thalassemia gene assay utilized a two-tier multiplex polymerase chain reaction amplification system and one round of hybridization. Genomic DNA samples were sourced from three hospitals in southern China. Each clinically validated DNA sample was re-evaluated using the new multiplex polymerase chain reaction/reverse dot blot assay III(M-PCR/RDB III). Results: The study analyzed a total of 1,148 unrelated participants, consisting of 810 thalassemia patients and 338 healthy control subjects. Valid hybridization results were obtained for 1,147 samples, with one case (thalassemia carrier) being excluded from the study due to the poor quality of DNA. All 1,147 samples, including those with α heterozygous thalassemia, α homozygous thalassemia, α compound heterozygous thalassemia, and control subjects were accurately genotyped, showing 100% concordance with the reference assays. Conclusion: The novel M-PCR/RDB III assay proved to be simple, rapid, and precise, indicating its potential for genetic screening and clinical diagnosis of both common and rare α-thalassemia variants in Chinese populations. [ABSTRACT FROM AUTHOR]

Background: β-thalassemia (β-TH) is a hereditary hemolytic anemia that results in deficient hemoglobin (Hb) synthesis. It is characterized by ineffective erythropoiesis, anemia, splenomegaly, and systemic iron overload. Exploration new potential biomarkers and drug candidates is important to facilitate the prevention and treatment of β-TH. Methods: We applied quasi-targeted metabolomics between wild type (Wt) and heterozygous β-TH mice (Th3/+), a model of non-transfusion-dependent β-TH intermedia, in plasma and peripheral blood (PB) cells. Futher data was deeply mined by Kyoto Encyclopedia of Genomes (KEGG) and machine algorithms methods. Results: Using KEGG enrichment analysis, we found that taurine and hypotaurine metabolism disorders in plasma and alanine, aspartate and glutamate metabolism disorders in PB cells. After systematically anatomize the metabolites by machine algorithms, we confirmed that alpha-muricholic acidUP and N-acetyl-DL-phenylalanineUP in plasma and Dl-3-hydroxynorvalineUP, O-acetyl-L-serineUP, H-abu-OHUP, S-(Methyl) glutathioneUP, sepiapterinDOWN, and imidazoleacetic acidDOWN in PB cells play key roles in predicting the occurrence of β-TH. Furthermore, Sepiapterin, Imidazoleacetic acid, Methyl alpha-Dglucopyranoside and alpha-ketoglutaric acid have a good binding capacity to hemoglobin E through molecular docking and are considered to be potential drug candidates for β-TH. Conclusion: Those results may help in identify useful molecular targets in the diagnosis and treatment of β-TH and lays a strong foundation for further research. [ABSTRACT FROM AUTHOR]

Objective: To study the mandibular changes in the β-thalassemia major patient. Study Design: Cross sectional study. Setting: Husaini Blood Bank and Institute of Hematological Diseases Karachi, Department of Oral and Maxillofacial Surgery, and Department of Orthodontics, Baqai Dental College Baqai Medical University, Karachi. Period: January 2023-December 2023. Methods: 50 Orthopanthogram (OPG) radiographs of beta-thalassemia major patient were taken, analyzed and compared to check any variation from normal. Fifty diagnosed β-thalassemia major patients were voluntarily selected through convenience sampling. The study was carried out in collaboration of Husaini Institute of Blood Diseases Karachi, National institute of Oral Diseases Karachi Pakistan and, Department of Oral and Maxillofacial Surgery and department of orthodontics Baqai Dental College Baqai Medical University. Results: 18 (36%) patient's alteration of trabecular pattern are present and in 32 (64%) patient alteration of trabecular pattern absent. Similarly, in 16 (32%) patients have short spiky roots are present and 34 (68%) patients short spiky roots absent. Conclusion: Effect of anemia is not so profound in mandible of thalassemia patients from population of Karachi. [ABSTRACT FROM AUTHOR]

Purpose: ß-thalassemia is a hereditary disorder due to mutation in the ß-globin gene on chromosome 11. Out of 200 known ß-globin gene chain mutations recognized, it is better to identify the most common mutation in specific regions and ethnicity for cost-effective molecular diagnosis of this disorder. Therefore, this study aims to practice multiplex-amplification refractory mutation system (ARMS) PCR on patients with thalassemia in Khyber Pakhtunkhwa (KP) to investigate the most common mutations in the ß-globin chain gene. Design/methodology/approach: Twenty-two individuals (patients, their parents and non-affected siblings) with signed consent were studied from six consanguineous families of ß-thalassemia. Blood samples were collected for DNA isolation. For the detection of mutations in the ß-globin gene, ARMS-PCR was used. The amplicon was visualized through 2% Agarose Gel. Findings: The most common mutations among different ethnic groups in the study area residents were Fr 8-9 (+G) and IVS 1-5 (G> C). The prominent enhancing factors for ß-thalassemia are inter-family marriages and lack of awareness. Practical implications: Multiplex ARMS_PCR is the most valuable technique for assessing multiple mutations in a single reaction tube. Social implications: Due to extensively found ethnic and regional variations and a high rate of consanguinity, the Pashtun population has a great risk of mutations in their genome. Therefore, ARMS-PCR is a cost-effective mutational diagnostic strategy that can help to control disease burden. Originality/value: Limited studies using ARMS-PCR for mutational analysis in the ß-globin gene are conducted. This study is unique as it targeted consanguineous families of KP Pakistan. [ABSTRACT FROM AUTHOR]

Objective: To look at patients with -thalassemia's skeletal patterns. Study Design: Cross sectional, Observational. Setting: Karachi Medical and Dental College, Baqai Dental College Baqai Medical University, Husaini Institute of Heamatological Studies and Fatmid Foundation. Study Period: 2012 to 2020. Methods: Fifty patients with major thalassemia were voluntarily chosen at random, and 50 lateral cephalometric X-rays were taken using the Steiner Analysis inclusion criteria major Thalassemia Patient under 35 without any systemic disorders. exclusion criterion any additional forms of thalassemia, as well as other systemic illnesses such as heart disease, diabetes, and down syndrome, patient age is greater than 35. Results: Patients with 50 thalassemic patients have an average ANB angle of 4.8 degree. No patients fit into Skeletal Class III, as indicated by the ANB ranges for 21 (42%) patients being between 2 and 2 o (0 to 4 o) and for 29 (58%) patients being above 4 o degree. Conclusion: 42% of beta thalassemia patients with Class 1 skeletal and orthoganathism. In 58% of cases, Class II and mandibular retroganathism are present. and there were no patients in skeletal class III found. The effects of anemia are less severe in patients from Karachi's thalassemia community. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin, being a hemoprotein, may operate as a peroxidase due to the hemolysis process and the release of heme into blood stream. Objective: Evaluation of the oxidative biomarkers and peroxidase activity of hemoglobin in patients with final stage of renal failure. Materials and Methods: The study encompassed a total of 200 blood samples, with 140 samples collected from patients diagnosed with Chronic Kidney Disease (CKD) and 60 samples obtained from individuals who were considered healthy control subjects. Results: Levels of various serum parameters, including total protein, urea, creatinine, albumin, free amino, disulfide, ischemia-modified albumin (IMA), peroxidase activity, and specific activity, exhibited a significant increase in patients with Chronic Kidney Disease (CKD) when compared to the control group consisting of healthy individuals. Conversely, CKD patients demonstrated a notable decrease in levels of glomerular filtration rate (GFR), hemoglobin, native thiols, and total thiols compared to the control group. Conclusion: Oxidative biomarkers may present useful information about the oxidative stress and help to diagnose CKD patients in their advanced stages of the disease. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDDs) are one of the prevailing conditions characterized by progressive neuronal loss. Polyadenylation (PA) and alternative polyadenylation (APA) are the two main post-transcriptional events that regulate neuronal gene expression and protein production. This systematic review analyzed the available literature on the role of PA and APA in NDDs, with an emphasis on their contributions to disease development. A comprehensive literature search was performed using the PubMed, Scopus, Cochrane, Google Scholar, Embase, Web of Science, and ProQuest databases. The search strategy was developed based on the framework introduced by Arksey and O'Malley and supplemented by the inclusion and exclusion criteria. The study selection was performed by two independent reviewers. Extraction and data organization were performed in accordance with the predefined variables. Subsequently, quantitative and qualitative analyses were performed. Forty-seven studies were included, related to a variety of NDDs, namely Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Disease induction was performed using different models, including human tissues, animal models, and cultured cells. Most investigations were related to PA, although some were related to APA or both. Amyloid precursor protein (APP), Tau, SNCA, and STMN2 were the major genes identified; most of the altered PA patterns were related to mRNA stability and translation efficiency. This review particularly underscores the key roles of PA and APA in the pathogenesis of NDDs through their mechanisms that contribute to gene expression dysregulation, protein aggregation, and neuronal dysfunction. Insights into these mechanisms may lead to new therapeutic strategies focused on the modulation of PA and APA activities. Further research is required to investigate the translational potential of targeting these pathways for NDD treatment., (© 2024 International Society for Neurochemistry.)

Seminars in Thrombosis and Hemostasis (STH) celebrates 50 years of publishing in 2024. To celebrate this landmark event, STH is republishing some archival material. This manuscript represents the first full paper ever published in STH. The manuscript published without an abstract, and essentially covered in considerable detail the molecular structure of fibrinogen, as was known at that time. Fittingly, it covers some historical perspectives, the physicochemical properties and structure of fibrinogen across several species of animals (including humans) and its transformation into fibrin. We hope the readers of STH enjoy this journey into the past. This manuscript is accompanied by a Commentary that reflects on this past, as well as the journey towards contemporary understanding of the molecular structure of fibrinogen. As this is a republication of archival material, transformed into a modern format, we apologise in advance for any errors introduced during this transformation. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Syntax Literate is the property of Ridwan Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Various abnormal hemoglobin structures of human blood are widely prevalent among some populations of Upper Assam. Over the years, various researches have been conducted by different researchers from varied perspectives. Many theories have been put forward as to the origin and spread of the mutation which led to the occurrence of abnormal hemoglobin in the Austro-Asiatic population of South East Asia and the Tibeto-Burman population of North- East India. Hypotheses stating its relation to malarial selection, inbreeding and fertility have also been ascertained. However, these studies have, time and again, reflected mixed results, as a holistic study on this topic is required. A systematic review of literature on platforms such as NCBI-MeSH, PubMed, Google Scholar, Scirus, etc., was done for the time period between 1950 to 2022. This study attempts to review all the researches done so far in North-East India vis-à-vis abnormal hemoglobin structure to trace the origin and prevalence of these hemoglobin types and unearth the gaps in the existing literature. [ABSTRACT FROM AUTHOR]

Indonesia is a large island country with a wide variety of ethnic groups. As part of the thalassemia country belt, Indonesia has alleles that are as distinctive as those found in other parts of Southeast Asia. The journey of ancestors in the prehistoric period and the massive increase in human exchange in the last decade have formed the current population of Indonesia. The mutants of the beta-thalassemia allele brought by those predecessors can be seen from the traces of their journey. This paperdescribes the flow gene according to the type of mutations of beta-thalassemia in the country. [ABSTRACT FROM AUTHOR]

The Cytokine-inducible Src homology 2 domain-containing (CISH) protein is a negative feedback regulator induced by cytokines that play key roles in immunity and erythropoiesis. Single nucleotide polymorphisms (SNPs) in the human CISH gene have been associated with increased susceptibility to severe malaria disease. To directly assess how CISH might influence outcomes in the BALB/c model of malaria anemia, CISH knockout (Cish-/-) mice on this background were infected with Plasmodium berghei and their hematopoietic responses, cytokine production and ability to succumb to severe malaria disease evaluated. Despite basal erythrocytic disruption, upon P. berghei infection, the Cish mice were better able to maintain peripheral blood cell counts, hemoglobin levels and a steady-state pattern of erythroid differentiation compared to wild-type (Cish +/+) mice. Ablation of CISH, however, did not influence the outcome of acute malaria infections in either the BALB/c model or the alternative C57BL/6 model of experimental cerebral malaria, with the kinetics of infection, parasite load, weight loss and cytokine responses being similar between Cish+/+ and Cish-/- mice, and both genotypes succumbed to experimental cerebral malaria within a comparable timeframe. [ABSTRACT FROM AUTHOR]

α-globin gene triplication carriers were not anemic in general, while some studies found that α-globin gene triplication coinherited with heterozygous β-thalassemia may cause adverse clinical symptoms, which yet lacks sufficient evidence in large populations. In this study, we investigated the prevalence and distribution of α-globin gene triplication as well as the phenotypic characteristics of α-globin gene triplication coinherited with heterozygous β-thalassemia in Ganzhou city, southern China. During 2021-2022, a total of 73,967 random individuals who received routine health examinations before marriage were genotyped for globin gene mutations by high-throughput sequencing. Among them, 1,443 were α-globin gene triplication carriers, with a carrier rate of 1.95%. The most prevalent mutation was αααanti3.7/αα (43.10%), followed by αααanti4.2/αα (38.12%). 42 individuals had coinherited α-globin gene triplication and heterozygous β-thalassemia. However, they did not differ from the individuals with heterozygous β-thalassemia and normal α-globin (αα/αα) in terms of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels. In addition, heterogenous clinical phenotypes were found in two individuals with the same genotype. Our study established a database of Ganzhou α-globin gene triplication and provided practical advice for the clinical diagnosis of α-globin gene triplication. [ABSTRACT FROM AUTHOR]

Objective: Here we investigate infectious diseases that potentially contribute to osteological lesions in individuals from the early medieval necropolis of La Olmeda (6th-11th c. CE) in North Iberia., Materials and Methods: We studied a minimum number of 268 individuals (33 adult females; 38 adult males, 77 unknown/indeterminate sex; and 120 non-adults), including articulated and commingled remains. Individuals with differential diagnoses suggesting chronic systemic infectious diseases were sampled and bioinformatically screened for ancient pathogen DNA., Results: Five non-adults (and no adults) presented skeletal evidence of chronic systemic infectious disease (1.87% of the population; 4.67% of non-adults). The preferred diagnoses for these individuals included tuberculosis, brucellosis, and malaria. Ancient DNA fragments assigned to the malaria-causing pathogen, Plasmodium spp., were identified in three of the five individuals. Observed pathology includes lesions generally consistent with malaria; however, additional lesions in two of the individuals may represent hitherto unknown variation in the skeletal manifestation of this disease or co-infection with tuberculosis or brucellosis. Additionally, spondylolysis was observed in one individual with skeletal lesions suggestive of infectious disease., Conclusions: This study sheds light on the pathological landscape in Iberia during a time of great social, demographic, and environmental change. Genetic evidence challenges the hypothesis that malaria was absent from early medieval Iberia and demonstrates the value of combining osteological and archaeogenetic methods. Additionally, all of the preferred infectious diagnoses for the individuals included in this study (malaria, tuberculosis, and brucellosis) could have contributed to the febrile cases described in historical sources from this time., (© 2024 The Author(s). American Journal of Biological Anthropology published by Wiley Periodicals LLC.)

In temperate and subtropical regions, ancient proteins are reported to survive up to about 2 million years, far beyond the known limits of ancient DNA preservation in the same areas. Accordingly, their amino acid sequences currently represent the only source of genetic information available to pursue phylogenetic inference involving species that went extinct too long ago to be amenable for ancient DNA analysis. Here we present a complete workflow, including sample preparation, mass spectrometric data acquisition and computational analysis, to recover and interpret million-year-old dental enamel protein sequences. During sample preparation, the proteolytic digestion step, usually an integral part of conventional bottom-up proteomics, is omitted to increase the recovery of the randomly degraded peptides spontaneously generated by extensive diagenetic hydrolysis of ancient proteins over geological time. Similarly, we describe other solutions we have adopted to (1) authenticate the endogenous origin of the protein traces we identify, (2) detect and validate amino acid variation in the ancient protein sequences and (3) attempt phylogenetic inference. Sample preparation and data acquisition can be completed in 3-4 working days, while subsequent data analysis usually takes 2-5 days. The workflow described requires basic expertise in ancient biomolecules analysis, mass spectrometry-based proteomics and molecular phylogeny. Finally, we describe the limits of this approach and its potential for the reconstruction of evolutionary relationships in paleontology and paleoanthropology., (© 2024. Springer Nature Limited.)

Objectives. The primary aim of this study was to evaluate the prevalence of iron overload and the real-world clinical effectiveness of the iron chelation therapies (ICTs) in Syrian patients with transfusion-dependent beta thalassemia major (BTM) prior to and during the ongoing Syrian conflict. Methods. This single-center, two-stage observational study was conducted at Homs National Thalassemia Center (HNTC) prior to (2009) and during (2019) the armed conflict. The prevalence and the severity of iron overload, as well as the effectiveness of four iron chelation regimens, were assessed using serum ferritin (SF) concentrations as a means of monitoring in two cohorts of BTM patients receiving deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), or a combination of DFO and DFP therapy in both years. Statistical analyses encompassed one-way ANOVA, Kruskal-Wallis, Mann–Whitney U, and chi-square (χ2) tests for the comparisons of the variables and the frequencies between the two cohorts and subgroups. Results. We included all eligible BTM patients at HNTC in 2009 (n = 205) and 2019 (n = 172). Only 84 patients from the 2009 cohort were accessible in 2019. Our findings revealed that 98% and 89% of the patients had iron overload (S F ≥ 1500 ng/mL) and comparable elevated median SF concentrations (3868 and 3757 ng/mL) in 2009 and 2019, respectively (P = 0.275). Furthermore, patients on DFO demonstrated the poorest control of iron overload and the highest SF concentrations (4319 and 5586 ng/mL), whereas those on DFX achieved superior outcomes and the lowest SF concentrations (3355 and 2152 ng/mL) in both years. Twenty-six patients from the 2019 cohort received no ICT for six years (from 2012 to 2018) and experienced extremely severe iron overload with SF levels ranging between 4481 and 16,000 ng/mL. Conclusions. Our findings prove a high prevalence of iron overload and suboptimal chelation outcomes in Syrian BTM patients, both prior to and during the ongoing armed conflict, despite the provision of free ICTs at HNTC. Poor adherence and older age of patients may explain the unfavorable outcomes of DFO and (DFO+DFP) regimens, whereas younger age and higher socioeconomic status may have contributed to the lowest SF and superior outcomes in patients on DFX. This study also demonstrates the crucial role of the National Thalassemia Centers, namely HNTC, in providing health services to BTM patients in times of peace and conflict. [ABSTRACT FROM AUTHOR]

Oxygen transport from the lungs to peripheral tissue is dependent on the affinity of hemoglobin for oxygen. Recent experimental data have suggested that the maximum human capacity for oxygen uptake and utilization (V̇O2max) at sea level and altitude (~3000 m) is sensitive to alterations in hemoglobin‐oxygen affinity. However, the effect of such alterations on V̇O2max at extreme altitudes remains largely unknown due to the rarity of mutations affecting hemoglobin‐oxygen affinity. This work uses a mathematical model that couples pulmonary oxygen uptake with systemic oxygen utilization under conditions of high metabolic demand to investigate the effect of hemoglobin‐oxygen affinity on V̇O2max as a function of altitude. The model includes the effects of both diffusive and convective limitations on oxygen transport. Pulmonary oxygen uptake is calculated using a spatially‐distributed model that accounts for the effects of hematocrit and hemoglobin‐oxygen affinity. Systemic oxygen utilization is calculated assuming Michaelis–Menten kinetics. The pulmonary and systemic model components are solved iteratively to compute predicted arterial and venous oxygen levels. Values of V̇O2max are predicted for several values of hemoglobin‐oxygen affinity and hemoglobin concentration based on data from humans with hemoglobin mutations. The model predicts that increased hemoglobin‐oxygen affinity leads to increased V̇O2max at altitudes above ~4500 m. [ABSTRACT FROM AUTHOR]

Objectives: We test the hypothesis that the condition(s) leading to the development of cribra orbitalia at Con Co Ngua, an early seventh millennium sedentary foraging community in Vietnam, effectively reduced the resilience of the population to subsequent health/disease impacts. An assessment of both the implications and potential etiology of cribra orbitalia in this specific population is carried out. Methods: The effective sample included 141 adults aged ≥15 years (53 females, 71 males, and 17 unknown sex) and 15 pre‐adults aged ≤14 years. Cribra orbitalia was identified by way of cortical bone porosity of the orbital roof initiated within the diplöic space, rather than initiated subperiosteally. The approach is also robust to the misidentification of various pseudo‐lesions. Resultant data was analyzed using Kaplan–Meier survival analysis. Results: Median survival is higher in adults aged ≥15 years without cribra orbitalia than those with this lesion. For the pre‐adult cohort, the opposite pattern is seen where median survival is higher in those with cribra orbitalia than those without. Conclusion: Adults displayed increased frailty and pre‐adults increased resilience with respect to cribra orbitalia. The differential diagnosis for a survival analysis of adults and pre‐adults with and without cribra orbitalia included iron deficiency anemia and B12/folate deficiency, parasitism (including hydatid disease and malaria) in addition to thalassemia. The most parsimonious explanation for observed results is for both thalassemia and malaria being the chief etiological agents, while appreciating these conditions interact with, and can cause, other forms such as hematinic deficiency anemias. [ABSTRACT FROM AUTHOR]

Background: Alpha thalassemia is one of the most common human genetic abnormalities. More than 400 different variations of the α-globin protein have been introduced, most of which are not associated with noticeable clinical manifestations. The identification of all variants of Hb in different regions helps in acquiring comprehensive knowledge concerning thalassemia disease, and it can be used in preventive programs as well as prenatal diagnosis (PND). Aims: In the present study, we describe a new α1 gene mutation that leads to a frameshift after codon 83. Methods: As a plan for a national screening program of thalassemia, routine cell blood count (CBC) and Hb capillary electrophoresis tests were applied. After taking written informed consent, genomic DNA was extracted, and, for identifying common Mediterranean α-Globin gene deletion, multiplex Gap-PCR was performed; for detecting other mutations on α- and β-Globin genes, a DNA sequencing method was used. Results: The results of CBC and capillary electrophoresis tests showed microcytosis in a female subject. The sequencing of the α-Globin gene showed that the case is heterozygote for a single-nucleotide deletion at codon 83 of the α1-Globin Gene. We named this mutation Hb Adrian (α1: c.251-T), which is a novel mutation. The mentioned mutation was also detected in the subject's mother. Conclusions: The introduced mutation (Hb Adrian) leads to a frameshift change that produces a protein with 100 amino acids, which in comparison to a normal α-chain is shorter, and its amino acids are altered after codon 83. This hemoglobin is undetectable via the use of electrophoresis. Although no major hematological abnormalities were observed in the carriers, Hb Adrian should be considered in screening programs to help prevent Hb H disease in high-risk couples. [ABSTRACT FROM AUTHOR]

Translation of mRNAs containing premature termination codons (PTCs) results in truncated protein products with deleterious effects. Nonsense-mediated decay (NMD) is a surveillance pathway responsible for detecting PTC containing transcripts. Although the molecular mechanisms governing mRNA degradation have been extensively studied, the fate of the nascent protein product remains largely uncharacterized. Here, we use a fluorescent reporter system in mammalian cells to reveal a selective degradation pathway specifically targeting the protein product of an NMD mRNA. We show that this process is post-translational and dependent on the ubiquitin proteasome system. To systematically uncover factors involved in NMD-linked protein quality control, we conducted genome-wide flow cytometry-based screens. Our screens recovered known NMD factors but suggested that protein degradation did not depend on the canonical ribosome-quality control (RQC) pathway. A subsequent arrayed screen demonstrated that protein and mRNA branches of NMD rely on a shared recognition event. Our results establish the existence of a targeted pathway for nascent protein degradation from PTC containing mRNAs, and provide a reference for the field to identify and characterize required factors. [ABSTRACT FROM AUTHOR]

Anemia is a major public health concern. Young children, menstruating adolescent girls and women, and pregnant women are among the most vulnerable. Anemia is the consequence of a wide range of causes, including biological, socioeconomic, and ecological risk factors. Primary causes include: iron deficiency; inherited red blood cell disorders; infections, such as soil‐transmitted helminthiasis, schistosomiasis, and malaria; gynecological and obstetric conditions; and other chronic diseases that lead to blood loss, decreased erythropoiesis, or destruction of erythrocytes. The most vulnerable population groups in low‐ and middle‐income countries are often at the greatest risk to suffer from several of these causes simultaneously as low socioeconomic status is linked with an increased risk of anemia through multiple pathways. Targeted and effective action is needed to prevent anemia. Understanding the causes and risk factors of anemia for different population subgroups within a country guides the design and implementation of effective strategies to prevent and treat anemia. A coordinated approach across various expert groups and programs could make the best use of existing data or could help to determine when newer and more relevant data may need to be collected, especially in countries with a high anemia burden and limited information on the etiology of anemia. [ABSTRACT FROM AUTHOR]

β-Thalassemia is an inherited hematological disorder that results from genetic changes in the β-globin gene, leading to the reduced or absent synthesis of β-globin. For several decades, the only curative treatment option for β-thalassemia has been allogeneic hematopoietic cell transplantation (allo-HCT). Nonetheless, rapid progress in genome modification technologies holds great potential for treating this disease and will soon change the current standard of care for β-thalassemia. For instance, the emergence of the CRISPR/Cas9 genome editing platform has opened the door for precision gene editing and can serve as an effective molecular treatment for a multitude of genetic diseases. Investigational studies were carried out to treat β-thalassemia patients utilizing CRISPR-based CTX001 therapy targeting the fetal hemoglobin silencer BCL11A to restore γ-globin expression in place of deficient β-globin. The results of recently carried out clinical trials provide hope of CTX001 being a promising one-time therapeutic option to treat β-hemoglobinopathies. This review provides an insight into the key scientific steps that led to the development and application of novel CRISPR/Cas9–based gene therapies as a promising therapeutic platform for transfusion-dependent β-thalassemia (TDT). Despite the resulting ethical, moral, and social challenges, CRISPR provides an excellent treatment option against hemoglobin-associated genetic diseases. [ABSTRACT FROM AUTHOR]

Transfusion-dependent thalassemia is the most severe form of thalassemia; patients require regular blood transfusions to maintain their hemoglobin level. The COVID-19 pandemic has disrupted the routine measures for controlling chronic diseases like thalassemia. This study aims to measure the difference in pre-transfusion hemoglobin levels and the frequency of transfusions before and during pandemic. This retrospective cross-sectional study utilized medical record data of 101 transfusion-dependent thalassemia (TDT) patients treated in Cipto Mangunkusumo Hospital (CMH) from 2019–2021. The dependent variables of this study were pre-transfusion hemoglobin level and transfusion attendance. The pre-pandemic phase was defined as 30 March 2019 to 29 March 2020, whereas the during-pandemic phase was from 30 March 2020 to 29 March 2021. Up to 59.4% of subjects had suboptimal Hb levels of <9.0 g/dL, even before the pandemic, and this increased to 71.3% during the pandemic. The mean pre-transfusion hemoglobin level before the pandemic was 8.71 g/dL, and this decreased to 8.46 g/dL (p value < 0.001). Transfusion attendance before and during the pandemic showed no significant difference (p-value = 0.990). Our study shows poorer control of pre-transfusion Hb levels during the pandemic. This puts patients at higher risk of developing many long-term complications. [ABSTRACT FROM AUTHOR]

Introduction: The α‐globin fusion gene between the HBA2 and HBAP1 genes becomes clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combining with α0‐thalassemia (α0‐thal). Due to its uncommon rearrangement in the α gene cluster without dosage changes, this fusion gene is undetectable by common molecular testing approaches used for α‐thal diagnosis. Methods: In this study, we used the single‐molecule real‐time (SMRT) sequencing technique to detect this fusion gene in 23 carriers identified by next‐generation sequencing (NGS) among 16,504 screened individuals. Five primers for α and β thalassemia were utilized. Results: According to the NGS results, the 23 carriers include 14 pure heterozygotes, eight compound heterozygotes with common α‐thal alleles, and one homozygote. By using SMRT, the fusion mutant was successfully detected in all 23 carriers. Furthermore, SMRT corrected the diagnosis in two "pure" heterozygotes: one was compound heterozygote with anti‐3.7 triplication, and the other was homozygote. Conclusion: Our results indicate that SMRT is a superior method compared to NGS in detecting the α fusion gene, attributing to its efficient, accurate, and one‐step properties. [ABSTRACT FROM AUTHOR]

Methylenetetrahydrofolate reductase (MTHFR) plays a major role in the metabolism of folates and homocysteine, which in turn can affect gene expression and ultimately promote the development of breast cancer. Thus, mutations in the MTHFR gene could influence homocysteine, methionine, and S-adenosylmethionine levels and, indirectly, nucleotide levels. Imbalance in methionine and S-adenosylmethionine synthesis affects protein synthesis and methylation. These changes, which affect gene expression, may ultimately promote the development of breast cancer. We therefore hypothesized that such mutations could also play an important role in the occurrence and pathogenesis of breast cancer in a Malian population. In this study, we used the PCR-RFLP technique to identify the different genotypic profiles of the C677T MTHFR polymorphism in 127 breast cancer women and 160 healthy controls. The genotypic distribution of the C677T polymorphism in breast cancer cases was 88.2% for CC, 11.0% for CT, and 0.8% for TT. Healthy controls showed a similar distribution with 90.6% for CC, 8.8% for CT, and 0.6% for TT. We found no statistical association between the C677T polymorphism and breast cancer risk for the codominant models CT and TT p > 0.05 . The same trend was observed when the analysis was extended to other genetic models, including dominant (p  = 0.50), recessive (p  = 0.87), and additive (p  = 0.50) models. The C677T polymorphism of MTHFR gene did not influence the risk of breast cancer in the Malian samples. [ABSTRACT FROM AUTHOR]

Thalassemia, as the most common single-gene genetic disorder, is related to a defect in the synthesis of one or more hemoglobin chains. More than 200 mutations have been identified in the β-globin gene. Globally, every susceptible racial group has its own specific spectrum of the common mutations that are well-known to a particular geographic region. On the other hand, varying numbers of diverse rare mutations may occur. The subjects of the study included 2113 heterozygote or homozygote β-thalassemia cases selected among couples who participated in the Iranian national thalassemia screening program from January 2011 to November 2019. Molecular characterization of the β-thalassemia mutation was initially carried out by the amplification-refractory mutation system-polymerase chain reaction (ARMS–PCR) technique for common mutations, followed by sequencing, Gap PCR, and Multiple ligation-dependent probe amplification (MLPA) methods - in cases not detected by the ARMS-PCR. The existence of 39 rare and new point mutations and 4 large deletions were described in our cohort. Sicilian (-13,337bp) deletion, CD36/37 (-T), and CD15 TGG>TGA were encountered more often than the others in a decreasing order, in terms of frequency. The least frequent mutations/deletions were deletion from HBD exon 1 to HBB promoter, 619 bp deletion, Deletion from up HBBP1-Exon3 HBBP1 and up HBB-0.5Kb down HBB, CAP+8 C>A, CD37 (G>A), CD6 (-A), IVSI-2 (T>C), IVSII-705 T>G, and IVSII-772 (G>A). Each occurred once. Five mutations/variants were also determined which have not been reported previously in Iran. According to the findings of the study, the Northwestern Iranian population displayed a wide variety of thalassemia allelic distributions. Identification of rare and new mutations in the β-thalassemia in the national population is beneficial for screening programs, genetic counseling, and prenatal diagnosis [ABSTRACT FROM AUTHOR]

The economically important Southern bluefintuna (Thunnus maccoyii) is a world-famous fast-swimming fish, but its genomic information is limited. Here, we performed whole genome sequencing and assembled a draft genome for Southern bluefin tuna, aiming to generate useful genetic data for comparative functional prediction. The final genome assembly is 806.54 Mb, with scaffold and contig N50 values of 3.31 Mb and 67.38 kb, respectively. Genome completeness was evaluated to be 95.8%. The assembled genome contained 23,403 protein-coding genes and 236.1 Mb of repeat sequences (accounting for 29.27% of the entire assembly). Comparative genomics analyses of this fast-swimming tuna revealed that it had more than twice as many hemoglobin genes (18) as other relatively slow-moving fishes (such as seahorse, sunfish, and tongue sole). These hemoglobin genes are mainly localized in two big clusters (termed as "MN" and "LA" respectively), which is consistent with other reported fishes. However, Thr39 of beta-hemoglobin in the MN cluster, conserved in other fishes, was mutated as cysteine in tunas including the Southern bluefin tuna. Since hemoglobins are reported to transport oxygen efficiently for aerobic respiration, our genomic data suggest that both high copy numbers of hemoglobin genes and an adjusted function of the beta- hemoglobin may support the fast-swimming activity of tunas. In summary, we produced a primary genome assembly and predicted hemoglobin-related roles for the fast-swimming Southern bluefintuna. [ABSTRACT FROM AUTHOR]

The association between heritability of venous thromboembolism (VTE) and thrombophilia was first reported clinically in 1956, later followed by the first description of a congenital cause of hypercoagulability—antithrombin deficiency—in 1965. Since then, our knowledge of hereditary causes of hypercoagulability, which may predispose carriers to VTE has improved greatly. Novel genetic defects responsible for severe thrombophilia have been recently identified and we have learned that a wide range of interactions between thrombophilia and other genetic and acquired risk factors are important determinants of the overall individual risk of developing VTE. Furthermore, therapeutic strategies in thrombophilic patients have benefited significantly from the introduction of direct oral anticoagulants. The present review is an overview of the current knowledge on the mechanisms underlying inherited thrombophilia, with a particular focus on the latest achievements in anticoagulation protocols and prevention strategies for thrombosis in carriers of this prothrombotic condition. [ABSTRACT FROM AUTHOR]

Background: The mouse model of human diseases is commonly used for biomedical study, including ß-thalassemia (ß-thal), an inherited hemoglobin disorder. Maintaining the mice strain by natural mating systems is costly and seems impractical, especially during the COVID-19 pandemic. Sperm-freezing is a cost-effective solution for ß-thal mouse colony management. Aim: To determine appropriate cryopreservation media for ß-thal mouse spermatozoa to establish a ß-thal mouse sperm bank. Methods: The epididymal spermatozoa of C57BL/6 wild-type (WT) and ß-globin gene knockout thalassemia (BKO) mice were frozen in four freezing media: I) raffinose-skim milk-monothioglycerol (MTG), II) raffinose-skim milk-glutamine, III) raffinose-egg yolk-glycerol, and IV) egg yolk-TES-Tris. The sperm quality was assessed prior to and following freeze-thawing. Results: Compared with WT counterparts, the viable spermatozoa before freezing exhibiting elevated levels of oxidative stress were significantly greater in BKO (p = 0.01). After thawing, the membrane integrity of BKO spermatozoa preserved in I was significantly lower (p = 0.001). The sperm viability and membrane integrity of BKO males were also inferior when media III and IV were used (p = 0.008-0.027). The amount of oxidative stress in the spermatozoon of BKO mice was significantly greater when preserved in I, III, and IV (p = 0.002-0.044). Comparing freezing media, the motility and acrosome integrity of WT and BKO spermatozoa preserved in IV were significantly higher than those in other media (p < 0.001 to p = 0.01). Spermatozoa with the highest mitochondrial membrane potential were observed in I in both genotypes (p = 0.012 to p > 0.05). The viability, membrane integrity, and oxidative stress of post-thaw BKO spermatozoa did not significantly differ among freezing solutions. Conclusion: Irrespective of freezing media, spermatozoa of BKO males are rather more sensitive to cryopreservation than those of WT. Raffinose-skim milk-MTG/glutamine, raffinose-egg yolk-glycerol, and egg yolk-TES-Tris can all be used to preserve BKO mouse spermatozoa. However, with slightly better sperm characteristics, egg yolk-TES-Tris may be a diluent of choice for BKO mouse sperm cryopreservation. The addition of a reducing agent to thawing media is also strongly recommended to efficiently prevent oxidative stress and therefore improve frozen-thawed sperm survival. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) is a rare side effect of hormonal therapy in transgender persons. Prothrombotic genetic variants can increase this risk. For this reason, previous VTE and/or genetic thrombophilia may be considered by some as contraindications to hormonal treatment. Aim: To formulate directions for clinical practice about the indications for thrombophilia screening and when to consider combination therapy of therapeutic anticoagulation and hormonal treatment as a safe alternative to withholding hormonal treatment. Methods: We conducted a literature search and describe a case series. All adult patients with gender dysphoria and a known prothrombotic genetic variant or history of VTE were invited by letter to participate in this study. Results: In our center, thrombophilia screening before start of hormonal treatment was restricted to those with a personal or family history of VTE. Sixteen individuals with a history of VTE and/or an underlying prothrombogenic condition were described. The time of follow up varied from 4 months to 20 years. Seven trans women had a positive thrombophilia screening (2 Factor V Leiden (FVL), 1 FVL + anticardiolipin antibodies, 1 FVL + high Factor VIII coagulant activity, 1 protein C deficiency, 1 prothrombin mutation, 1 positive lupus anticoagulant). Three trans women experienced an unprovoked VTE after start of hormonal therapy of which one lead to a positive thrombophilia screening. One VTE event in a trans woman was assumed to be provoked by surgery. Five trans men were identified with a prothrombogenic mutation (3 FVL, 1 protein C deficiency, 1 prothrombin mutation). One trans man, with a negative thrombophilia screen, experienced multiple provoked VTE events before start of hormonal therapy. Conclusion: Based on our literature review and case series we offer guidance when confronted with patients with previous VTE and/or genetic thrombophilia requesting hormonal interventions. [ABSTRACT FROM AUTHOR]

Background: Hemoglobinopathies, inherited disorders of hemoglobin (Hb), are the most common hereditary monogenic diseases of the red cell in the world. Few studies have been conducted on hemoglobinopathies in Mauritania. Therefore, the aim of this work is to establish the molecular and epidemiological basis of hemoglobinopathies in a cohort of Mauritanian patients and to determine the haplotype of the β‐globin gene cluster in sickle cell subjects. Methods: The molecular screening of Hb disorders in 40 Mauritanian patients was done by a polymerase‐restriction fragment length polymorphism (RFLP) for the sickle cell disease (SCD) mutation, a PCR/sequencing method for β‐thalassemia mutations, and by the multiplex polymerase chain reaction method for the α‐thalassemia. The exploration of eight polymorphic sites (SNPs) within the β‐globin gene cluster was conducted by PCR/RFLP method, to identify the HbS haplotypes from the sickle cell subjects. Results: The epidemiological study of our patients showed a high incidence in the Senegal River area (52.5%) and a high ethnic prevalence for the Heratin (47.5%) and the Pular (35%). Molecular study allowed us to identify eight different mutations in our sample analyzed. They are respectively: HbS (HBB:c.20A>T) (68.75%), Cd44 ‐C (HBB:c.135delC) (8.75%), −29A>G (HBB:c.‐79A>G) (4.8%), −α‐3.7 (g.34164_37967del3804) (3.75%), IVS‐II‐849A>G (HBB:c.316‐2A>G) (2.25%) and Cd24T>A (HBB:c.75T>A), Hb Siirt (HBB:c.83C>G) and HbC (HBB:c.19G>A) each with (1.25%). Six different haplotypes are being explored among the SCD subjects with the Senegal haplotype as the most prevalent (66.7%), followed by Benin (10%), Arab‐Indians (6.7%), Bantu (3.3%), and two atypical haplotypes. Conclusion: Our findings enrich the epidemiological data in our population and could contribute to the establishment of a strategy of prevention and management through screening, genetic counseling, and prenatal diagnosis of Hemoglobinopathies in the Mauritanian population. [ABSTRACT FROM AUTHOR]

This study investigated the impacts of CCR5 promoter region polymorphisms on the development of systemic lupus erythematosus (SLE) by comparing CCR5 genotypes and haplotypes from SLE patients with ethnically matched controls. A total of 382 SLE patients (289 European-derived and 93 African-derived) and 375 controls (243 European-derived and 132 African-derived) were genotyped for the CCR2-64I G > A (rs1799864), CCR5-59353 C > T (rs1799988), CCR5-59356 C > T (rs41469351), CCR5-59402 A > G (rs1800023) and CCR5-59653 C > T (rs1800024) polymorphisms through polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Previous data from CCR5Δ32 analysis was included in the study to infer the CCR5 haplotypes and as a possible confounding factor in the binary logistic regression. European-derived patients showed a higher frequency of CCR5 wild-type genotype (conversely, a reduced frequency of Δ32 allele) and a reduced frequency of the HHG*2 haplotype compared to controls; both factors significantly affecting disease risk [p = .003 (OR 3.5, 95%CI 1.6-7.5) and 2.0% vs. 7.2% (residual p = 2.9E - 5), respectively]. Additionally, the HHA/HHB, HHC and HHG*2 haplotype frequencies differed between African-derived patients and controls [10% vs. 20.5% (residual p = .003), 29.4% vs. 17.4% (residual p = .003) and 3.9% vs. 0.8% (residual p = .023), respectively]. Considering the clinical manifestations of the disease, the CCR5Δ32 presence was confirmed as a susceptibility factor to class IV nephritis in the African-derived group and when all patients were grouped for comparison [p corrected  = .012 (OR 3.0; 95%CI 3.0-333.3) and p corrected  = .0006 (OR 6.8; 95%CI 1.9-24.8), respectively]. In conclusion, this study indicates that CCR5 promoter polymorphisms are important disease modifiers in SLE. Present data reinforces the CCR5Δ32 polymorphism as a protective factor for the development of the disease in European-derived patients and as a susceptibility factor for class IV nephritis in African-derived patients. Furthermore, we also described a reduced frequency of HHA/HHB and an increased frequency of HHC and HHG*2 haplotypes in African-derived patients, which could modify the CCR5 protein expression in specific cell subsets., (© 2023 John Wiley & Sons Ltd.)

Venous thromboembolism (VTE) is a life-threatening complication, especially in case of recurrence. The appropriate duration of anticoagulant treatment following the first event is crucial. Risk factors that increase the risk of recurrence of VTE are many, and include medications, kidney disease, renal transplantation (RT), and a diagnosis of sickle cell disease (SCD). There are currently no guidelines that define the duration of anticoagulant therapy after the first event in a patient with RT. We report a case of recurring episodes of VTE after RT in a SCD patient. Our case suggests that the use of a long-term anticoagulant treatment may be recommended in patients with SCD and RT after the first event of VTE. [ABSTRACT FROM AUTHOR]

Alpha thalassemia is an autosomal recessive disorder caused by large deletions and/or point mutations in the α-globin genes. Hemoglobin H (Hb H) disease is most frequently due to deletion of three of the four α globin genes associated with variable clinical severity depending on the genotype. There are few reports on Hb H disease in Indians where genotyping has been done and we have reviewed the molecular and clinical heterogeneity of these cases. An electronic search for relevant articles was conducted using two journal databases, i.e., PubMed and Science Direct using the key words "Hb H Disease", "Hemoglobin H", "α-thalassemia", "mutations", "molecular heterogeneity", "case reports" and "India". This review was performed based on preferred reporting items for the systematic review and meta-analysis protocols (PRISMA-P) guidelines. The molecular spectrum of Hb H disease in Indians includes the most common [-α3.7, -α4.2, -SA, Poly A (AATAAA!AATA-), Hb Sallanches], rare [-SEA, -MED, IVS 1nt 1 (G!A), Hb Koya Dora, Hb Sun Prairie], very rare [Hb Iberia, Hb Seal Rock, Hb Zürich-Albisrieden] and novel [Codon 76 (+T) and -Kol] α-globin gene mutations inherited largely as compound heterozygotes with considerable clinical variability. The molecular diagnosis of Hb H disease is important for genetic counseling and management. [ABSTRACT FROM AUTHOR]

Recently, researchers in our laboratory have shown that humans with genetic mutations resulting in high-affinity haemoglobin (HAH) demonstrate better maintained aerobic capacity and peak power output during hypoxic exercise versus normoxic exercise in comparison to humans with normal-affinity haemoglobin. However, the influence of HAH on tissue oxygenation within exercising muscle during normoxia and hypoxia is unknown. Therefore, we examined near-infrared spectroscopy-derived oxygenation profiles of the vastus lateralis during graded cycling exercise in normoxia and hypoxia among humans with HAH (n = 5) and control subjects with normal-affinity haemoglobin (n = 12). The HAH group elicited a blunted increase of deoxygenated haemoglobin+myoglobin during hypoxic exercise compared with the control group (P = 0.03), suggesting reduced fractional oxygen extraction in the HAH group. In addition, the HAH group maintained a higher level of muscle tissue oxygen saturation during normoxic exercise (HAH, 75 ± 4% vs. controls, 65 ± 3%, P = 0.049) and there were no differences between groups in muscle tissue oxygen saturation during hypoxic exercise (HAH, 68 ± 3% vs. controls, 68 ± 2%, P = 0.943). Overall, our results suggest that humans with HAH might demonstrate divergent patterns of fractional oxygen extraction during hypoxic exercise and elevated muscle tissue oxygenation during normoxic exercise compared with control subjects. [ABSTRACT FROM AUTHOR]

Background: β‐thalassemia syndromes are the most common hereditary blood disorders in the world and are recognized as a major health problem in Morocco. They are characterized by the reduction or the absence of β‐globin chain synthesis. The severity of the disease depends on the nature of the variants affecting the β‐globin gene (HBB), and each ethnic group has its own mutation spectrum. Hereby, we present, for the first time, the molecular profile of β‐thalassemia in the Eastern region of Morocco. Methods: This study concerns 39 cases from 33 families who were enrolled in the BRO Biobank. Nineteen were diagnosed with β‐thalassemia major and 20 with β‐thalassemia minor. To detect mutations of the β‐globin gene, we have used RFLP‐PCR and Sanger sequencing. Results: Nine known β‐thalassemia variants have been identified. Among these, we reported, for the first time in the Moroccan population, the Czechoslovakian variant C38/39(‐C) at homozygous state. The C39(C > T) was the most frequent variant (72.54%), followed by FSC5(‐CT) (5.88%), FSC6(−A), IVS‐1‐110(G > A), −29(A > G), C38/39(‐C) (3.92% each), and finally by IVS‐I‐1(G > A), IVS‐II‐1(G > A), and −56(G > C) (1.96%). Of particular interest this mutational spectrum of β‐thalassemia is very different from that found in previous studies in Morocco or in other North African countries. Conclusion: This study is the first contribution to the description of the molecular profile of β‐thalassemia in the Eastern region of Morocco. It shows the high molecular heterogeneity of β‐thalassemia in our country. Therefore, these results can be valuable for the implementation of carrier screening, genetic counseling, and prenatal diagnosis programs. [ABSTRACT FROM AUTHOR]

Patients with thalassemia major are exposed to a wide range of blood transition viruses that among them hepatitis B and C viruses are in high significance. This study investigates the seroprevalence of HBV and HCV in hospital admissions for thalassemia major in Bengbu, China. This study is a cross-sectional study in which information was extracted and collected from patients' records, including gender, age, number of blood transfusions per year, HBs-Ag, HCV-Ab and Anti-HBs. The study included 630 thalassemia major patients who received regular blood transfusions at a hospital in Bengbu, China. We found that out of 630 patients of the study, there were three HBs-Ag positive, so the prevalence of HBV in this study is 0.5%. The prevalence of HCV-Ab positive was 7.1 and these individuals had a significantly older mean age than those with HCV-Ab negative. In 89.8% of patients the HBs-Ab titer was more than 10. Due to the progress of screening and selection of blood donors the prevalence of HBV infection in high-risk patients has sharply decreased in recent years. Vaccination is one of the most important protective factors in this group of the population. Therefore, administration of a reminder dose based on antibody titer is recommended in these individuals. [ABSTRACT FROM AUTHOR]

Sickle cell disease is a set of illnesses characterized by the misshaping and breakdown of red blood cells. Red blood cells twist into a sickle shape in sickle cell disease, an inherited set of illnesses. The cells die early, resulting in a lack of healthy red blood cells (sickle cell anemia), and they might impede blood flow, causing pain (sickle cell crisis). Vernon Mason coined the term "sickle cell anemia" in 1922. SCD is thought to have killed approximately 114,800 individuals worldwide, and it is more common among people whose ancestors lived in tropical and subtropical sub-Saharan Africa, where malaria is or was prevalent. There are several types of SCD, including homozygous HbS and HbS/HbC co-inheritance (usually called HbSC). A genetic mutation causes the condition, which disrupts the ironrich molecule essential for making blood red and transporting oxygen. SCD has been treated using a variety of approaches. The use of hydroxycarbamide and L-glutamine, blood transfusions, bone marrow transplants, gene therapy, and nutritional supplementation are just a few of them. Gene therapy is the most effective treatment option on the list. The method relies on modifying and reprogramming cells from the patient's own blood cells, as well as genetic engineering, to fix the inborn genetic defect. hydroxyurea, on the other hand, has been shown to change the course of the disease. Finally, if utilized correctly, a combination of available therapeutic medications could greatly improve the disease. [ABSTRACT FROM AUTHOR]

The Bengali population groups of West Bengal, India was studied for CBC (complete blood count) for the screening of beta-thalassemia trait and other abnormal hemoglobin. Results of the present study were compared with available other studies. In the case of the beta-thalassemia trait, prediction of CBC value was 99.9% positive. And in the case of the HBE trait, frequency of CBC negative (65.67%) value was much higher than CBC positive (34.33%). Biological distance values show that the British and Turkish are comparatively close in this respect. While, the Sardinian, Pakistani and Indian (Bengali) are maintaining far distance among themselves. However, the study population maintains a relatively far distance with the British, Turkish, Sardinian and Pakistani in both the genders. [ABSTRACT FROM AUTHOR]

Introduction: Hemoglobinopathies are diverse group of inherited disorders of hemoglobin production and function. They represent the most common single-gene disorders that are found in humans and are distributed in various frequencies throughout the world. Pregnancy in women with sickle cell disease can increase the risk of maternal and perinatal mortality. HPLC offers the advantages over the routine Hemoglobin electrophoresis as it can more accurately identify and quantitate abnormal hemoglobin. HPLC forms an accurate, rapid and reproducible tool for early detection and management of thalassemia and abnormal hemoglobin variants. Material and Methods: This is an observational study was undertaken in the Department of Obstetrics & Gynaecology and Department of Hematology of S.C.B Medical College, Cuttack. During this period those pregnant women, who attended gynaecology OPD of SCB medical college, Cuttack were investigated during various months of gestations. All pregnant women were counselled and offered screening for hemoglobinopathies after informed and written consent. Results: Among the antenatal women with hemoglobinopathy, 90.91% were anemic, 09.09% were not anemic. Among the normal group 71.06% were anemic, 28.94% were not anemic. So, there was more prevalence of anaemia among hemoglobinopathy than normal subjects which was statistically significant. (p=0.004). Among the antenatal women with hemoglobinopathy, 92.86% with sickle cell disorder were anemic and 93.75% So out of total women with hemoglobinopathy 93.18% were anemic. In our study 4.55% of hemoglobinopathy cases came for first antenatal check-up before 12 weeks, 18.18% between 12-28 weeks, and 77.27% after 28 weeks. Among the normal group 9.03% came for first antenatal check-up before 12 weeks, 25.00% between 12-28 weeks, and 65.97 % after 28 weeks. Conclusion: Different types of hemoglobinopathies are prevalent in Odisha. Though it was thought earlier that hemoglobinopathies were more common in western Odisha, but due to population migration the incidence has increased in central and coastal Odisha. As pregnancy is greatly affected by hemoglobinopathy. The maternal morbidities like pre-eclampsia, preterm labour, Urinary tract infection, asymptomatic bacteriuria, antepartum hemorrhage and neonatal morbidities like low birth weight, FGR, SNCU admission rate, neonatal mortality increase in women with hemoglobinopathy. [ABSTRACT FROM AUTHOR]

Eukaryotic genomes are usually enriched in repetitive DNA sequences, which can be classified as dispersed or tandemly repeated elements. Satellite DNAs are noncoding monomeric sequences organized in a head-to-tail fashion that are generally located on the subtelomeric and/or pericentromeric heterochromatin. In general, a single species incorporates a diverse group of satellite DNA families, which collection is called satellitome. Here, we characterized three new satellitomes from distinct characid fish (Psalidodon fasciatus, P. bockmanni, and Astyanax lacustris) using a combination of genomic, cytogenetic, and bioinformatic protocols. We also compared our data with the available satellitome of P. paranae. We described 57 satellite DNA (satDNA) families of P. fasciatus (80 variants), 50 of P. bockmanni (77 variants), and 33 of A. lacustris (54 variants). Our analyses demonstrated that several sequences were shared among the analyzed species, while some were restricted to two or three species. In total, we isolated 104 distinctive satDNA families present in the four species, of which 10 were shared among all four. Chromosome mapping revealed that the clustered satDNA was mainly located in the subtelomeric and pericentromeric areas. Although all Psalidodon species demonstrated the same pattern of clusterization of satDNA, the number of clusters per genome was variable, indicating a high dynamism of these sequences. In addition, our results expand the knowledge of the As51 satellite DNA family, revealing that P. bockmanni and P. paranae exhibited an abundant variant of 39 bp, while P. fasciatus showed a variant of 43 bp. The majority of satDNAs in the satellitomes analyzed here presented a common library repetitive sequence in Psalidodon and Astyanax , with abundance variations in each species, as expected for closely related groups. In addition, we concluded that the most abundant satDNA in Psalidodon (As51) passed through a diversification process in this group, resulting in new variants exclusive of Psalidodon. [ABSTRACT FROM AUTHOR]

Hydroxyurea (HU) is a ribonucleotide reductase inhibitor most commonly used as a therapeutic agent in sickle cell disease (SCD) with the aim of reducing the risk of vaso-occlusion and improving oxygen transport to tissues. Previous studies suggest that HU may be even beneficial in mild anemia. However, the corresponding effects on skeletal muscle energetics and function have never been reported in such a mild anemia model. Seventeen mildly anemic HbAA Townes mice were subjected to a standardized rest-stimulation (transcutaneous stimulation)-protocol while muscle energetics using 31Phosphorus magnetic resonance spectroscopy and muscle force production were assessed and recorded. Eight mice were supplemented with hydroxyurea (HU) for 6 weeks while 9 were not (CON). HU mice displayed a higher specific total force production compared to the CON, with 501.35 ± 54.12 N/mm3 and 437.43 ± 57.10 N/mm3 respectively (+14.6%, p < 0.05). Neither the total rate of energy consumption nor the oxidative metabolic rate were significantly different between groups. The present results illustrated a positive effect of a HU chronic supplementation on skeletal muscle function in mice with mild anemia. [ABSTRACT FROM AUTHOR]