Alpha-thalassemia. Case report alpha-thalassemia in a Costa Rican family, A case report

This case report highlights the importance for health care providers to be aware of the αlpha‐thalassemia syndromes, their relevance to clinical care and family counseling, appropriate diagnostic algorithm for definitive diagnosis.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Hematología y Trastornos Afines (CIHATA

Mutations in the paralogous human α-globin genes yielding identical hemoglobin variants

The human α-globin genes are paralogues, sharing a high degree of DNA sequence similarity and producing an identical α-globin chain. Over half of the α-globin structural variants reported to date are only characterized at the amino acid level. It is likely that a fraction of these variants, with phenotypes differing from one observation to another, may be due to the same mutation but on a different α-globin gene. There have been very few previous examples of hemoglobin variants that can be found at both HBA1 and HBA2 genes. Here, we report the results of a systematic multicenter study in a large multiethnic population to identify such variants and to analyze their differences from a functional and evolutionary perspective. We identified 14 different Hb variants resulting from identical mutations on either one of the two human α-globin paralogue genes. We also showed that the average percentage of hemoglobin variants due to a HBA2 gene mutation (α2) is higher than the percentage of hemoglobin variants due to the same HBA1 gene mutation (α1) and that the α2/α1 ratio varied between variants. These α-globin chain variants have most likely occurred via recurrent mutations, gene conversion events, or both. Based on these data, we propose a nomenclature for hemoglobin variants that fall into this category

A phased SNP-based classification of sickle cell anemia HBB haplotypes

Background: Sickle cell anemia causes severe complications and premature death. Five common beta-globin gene cluster haplotypes are each associated with characteristic fetal hemoglobin (HbF) levels. As HbF is the major modulator of disease severity, classifying patients according to haplotype is useful. The first method of haplotype classification used restriction fragment length polymorphisms (RFLPs) to detect single nucleotide polymorphisms (SNPs) in the beta-globin gene cluster. This is labor intensive, and error prone. Methods: We used genome-wide SNP data imputed to the 1000 Genomes reference panel to obtain phased data distinguishing parental alleles. Results: We successfully haplotyped 813 sickle cell anemia patients previously classified by RFLPs with a concordance >98%. Four SNPs (rs3834466, rs28440105, rs10128556, and rs968857) marking four different restriction enzyme sites unequivocally defined most haplotypes. We were able to assign a haplotype to 86% of samples that were either partially or misclassified using RFLPs. Conclusion: Phased data using only four SNPs allowed unequivocal assignment of a haplotype that was not always possible using a larger number of RFLPs. Given the availability of genome-wide SNP data, our method is rapid and does not require high computational resources.NIH Bethesda, MDBoston Univ, Sch Med, Dept Med, 72 E Concord St, Boston, MA 02118 USABoston Univ, Bioinformat Program, Boston, MA 02215 USAKing Saud Univ, Coll Med, Sickle Cell Dis Res Ctr, Riyadh, Saudi ArabiaKing Saud Univ, Coll Med, Dept Pediat, Riyadh, Saudi ArabiaKing Faisal Univ, Al Omran Sci Chair, Al Hasa, Saudi ArabiaImam Abdulrahman bin Faisal Univ, Inst Res & Med Consultat, Dammam, Saudi ArabiaEscola Paulista Med, Hematol & Blood Transfus Div, São Paulo, BrazilBoston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USAEscola Paulista Med, Hematol & Blood Transfus Div, São Paulo, BrazilNIH: R01 HL 068970NIH: RC2 HL 101212NIH: R01 87681NIH: T32 HL007501Web of Scienc

Clinically relevant updates of the HbVar database of human hemoglobin variants and thalassemia mutations

HbVar (http://globin.bx.psu.edu/hbvar) is a widely-used locus-specific database (LSDB) launched 20 years ago by a multi-center academic effort to provide timely information on the numerous genomic variants leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Here, we report several advances for the database. We made clinically relevant updates of HbVar, implemented as additional querying options in the HbVar query page, allowing the user to explore the clinical phenotype of compound heterozygous patients. We also made significant improvements to the HbVar front page, making comparative data querying, analysis and output more user-friendly. We continued to expand and enrich the regular data content, involving 1820 variants, 230 of which are new entries. We also increased the querying potential and expanded the usefulness of HbVar database in the clinical setting. These several additions, expansions and updates should improve the utility of HbVar both for the globin research community and in a clinical setting

Treatment with Methylphenidate for Attention Deficit Hyperactivity Disorder (ADHD) and the Risk of All-Cause Poisoning in Children and Adolescents:A Self-Controlled Case Series Study

BACKGROUND: Children and adolescents with attention deficit hyperactivity disorder (ADHD) are at higher risk of all-cause poisoning by drugs and chemicals (intentional or accidental). Currently, there is limited data on whether medication treatment for ADHD can reduce the risk of all-cause poisoning. METHODS: Patients aged 5–18 years with a methylphenidate (MPH) prescription and an incident poisoning diagnosis between January 2001 and June 2020 were identified from the Hong Kong Clinical Data Analysis and Reporting System. A self-controlled case series study design was used to compare the incidence rate ratios (IRRs) of all-cause poisoning during different risk windows (30 days before the first MPH prescription, exposure periods within 30 days of the first prescription, and periods of subsequent exposure) compared with the reference window (other non-exposure periods). RESULTS: 42,203 patients were prescribed ADHD medication in Hong Kong during the study period. Of these, 417 patients who had both an MPH prescription and poisoning incident recorded were included in the main analysis. Compared with other non-exposed periods, a higher risk of poisoning was found in the 30 days before the first prescription (IRR 2.64, 95% confidence interval [CI] 1.33–5.22) and exposure periods within 30 days of the first prescription (IRR 2.18, 95% CI 1.06–4.48), but not during prolonged exposure. However, compared with 30 days before the first prescription as well as exposure periods within 30 days of the first prescription, there was a lower risk during the subsequent exposure (IRRs 0.49 and 0.60, respectively). Similar results to the main analysis were also found in the subgroup analysis of intentional poisoning and females, but not in that of accidental poisoning and males. CONCLUSIONS: The risk of all-cause poisoning was higher shortly before and after the first MPH prescription and became lower during the subsequent prescription period. Our results do not support an association between the use of MPH and an increased risk of all-cause poisoning in children and adolescents and, in fact, suggest that longer-term use of MPH may be associated with a lower risk of all-cause poisoning, although this latter finding requires further study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40263-021-00824-x

Legal determinants of external finance revisited : the inverse relationship between investor protection and societal well-being

This paper investigates relationships between corporate governance traditions and quality of life as measured by a number of widely reported indicators. It provides an empirical analysis of indicators of societal health in developed economies using a classification based on legal traditions. Arguably the most widely cited work in the corporate governance literature has been the collection of papers by La Porta et al. which has shown, inter alia, statistically significant relationships between legal traditions and various proxies for investor protection. We show statistically significant relationships between legal traditions and various proxies for societal health. Our comparative evidence suggests that the interests of investors may not be congruent with the interests of wider society, and that the criteria for judging the effectiveness of approaches to corporate governance should not be restricted to financial metrics

Criticality and Superfluidity in liquid He-4 under Nonequilibrium Conditions

We review a striking array of recent experiments, and their theoretical interpretations, on the superfluid transition in $^4$He in the presence of a heat flux, $Q$. We define and evaluate a new set of critical point exponents. The statics and dynamics of the superfluid-normal interface are discussed, with special attention to the role of gravity. If $Q$ is in the same direction as gravity, a self-organized state can arise, in which the entire sample has a uniform reduced temperature, on either the normal or superfluid side of the transition. Finally, we review recent theory and experiment regarding the heat capacity at constant $Q$. The excitement that surrounds this field arises from the fact that advanced thermometry and the future availability of a microgravity experimental platform aboard the International Space Station will soon open to experimental exploration decades of reduced temperature that were previously inaccessible.Comment: 16 pages, 9 figures, plus harvard.sty style file for references Accepted for publication in Colloquia section of Reviews of Modern Physic