Thalassemia, a human blood disorder

A group of inherited blood defects is known as Thalassemia is among the world’s most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Dynamic structural cell responses in the thymus to acute injury, regeneration, and age

The thymus, the primary site of T cell development, is extremely sensitive to insult but also harbors tremendous capacity for repair. Using single cell sequencing of thymic structural cells, as well as functional and structural analyses, we revealed distinct regenerative programs by endothelial and mesenchymal subsets after injury that stimulated epithelial repair; the compartment primarily supporting T cell development. Thymic function not only declined over lifespan, contributing to immune aging, but the capacity of the thymus to regenerate after damage also declined in old mice. This could be attributed to an inability of the old microenvironment to induce reparative programs; leading to reduced ability to restore tissue structure and function. These findings provide a detailed framework for the response of structural cells to aging and acute damage, which could have considerable implications for our understanding of aging immunity and recovery from treatments such as chemotherapy and bone marrow transplant.

Genetic Sex Validation for Sample Tracking in Clinical Testing

Background: Next generation DNA sequencing (NGS) has been rapidly adopted by clinical testing laboratories for detection of germline and somatic genetic variants. The complexity of sample processing in a clinical DNA sequencing laboratory creates multiple opportunities for sample identification errors, demanding stringent quality control procedures. Methods: We utilized DNA genotyping via a 96-SNP PCR panel applied at sample acquisition in comparison to the final sequence, for tracking of sample identity throughout the sequencing pipeline. The 96-SNP PCR panel's inclusion of sex SNPs also provides a mechanism for a genotype-based comparison to recorded sex at sample collection for identification. This approach was implemented in the clinical genomic testing pathways, in the multi-center Electronic Medical Records and Genomics (eMERGE) Phase III program. Results: We identified 110 inconsistencies from 25,015 (0.44%) clinical samples, when comparing the 96-SNP PCR panel data to the test requisition-provided sex. The 96-SNP PCR panel genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density hybridization-based genotyping arrays. Results identified clerical errors, samples from transgender participants and stem cell or bone marrow transplant patients and undetermined sample mix-ups. Conclusion: The 96-SNP PCR panel provides a cost-effective, robust tool for tracking samples within DNA sequencing laboratories, while the ability to predict sex from genotyping data provides an additional quality control measure for all procedures, beginning with sample collections. While not sufficient to detect all sample mix-ups, the inclusion of genetic versus reported sex matching can give estimates of the rate of errors in sample collection systems.

ADULT SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS – A CASE SERIES

Hemophagocytic lymphohistiocytosis is a hyper-inammatory condition that is either Familial (Primary) or Secondary to autoimmune diseases , infection, malignancy or other triggers.It is a cytokine storm syndrome where there inefcient antigen removal that leads to sustained cytokine release.It is a rare phenomenon occuring in adults that has got a specic trigger which is less documented and have a good response to steroids where as Familial form is a childhood disease due to genetic defects, both of which are life threatening and may need Allogenic bone marrow transplant. Macrophage activation syndrome is also a subtype of this entity that occurs in the treatment phase of SLE and Still's disease.We describe here 8 cases of secondary HLH, their primary triggers and treatment response.

Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection

Antiretroviral therapy (ART) effectively reduces cycles of viral replication but does not target proviral populations in cells that persist for prolonged periods and that can undergo clonal expansion. Consequently, chronic human immunodeficiency virus (HIV) infection is sustained during ART by a reservoir of long-lived latently infected cells and their progeny. This proviral landscape undergoes change over time on ART. One of the forces driving change in the landscape is the clonal expansion of infected CD4 T cells, which presents a key obstacle to HIV eradication. Potential mechanisms of clonal expansion include general immune activation, antigenic stimulation, homeostatic proliferation, and provirus-driven clonal expansion, each of which likely contributes in varying, and largely unmeasured, amounts to maintaining the reservoir. The role of clinical events, such as infections or neoplasms, in driving these mechanisms remains uncertain, but characterizing these forces may shed light on approaches to effectively eradicate HIV. A limited number of individuals have been cured of HIV infection in the setting of bone marrow transplant; information from these and other studies may identify the means to eradicate or control the virus without ART. In this review, we describe the mechanisms of HIV-1 persistence and clonal expansion, along with the attempts to modify these factors as part of reservoir reduction and cure strategies.

Corrigendum: Medical management of heavily exposed victims: an experience at the Tokaimura criticality accident (2021 J. Radiol. Prot. 41 S391)

In Akashi and Maekawa [1] an error occurred in figure 7 for “Treatment and clinical course of bone marrow of Worker B”. In this panel, the solid line showed the number of white blood cells, and the dot line presented the number of neutrophils. This figure was reprinted by permission from Ref [2] Springer Nature Copyright © 2002, Macmillan Publishers Limited. The line for the number of neutrophils was incorrect. A corrected version of the original figure 7 is given here in the figure 7. The correction here does not affect the major conclusions and the figure legend of the paper.References[1] Akashi M and Maekawa K 2021 J. Radiol. Prot. 41 S391–S405 10.1088/1361-6498/ac270d.[2] Nagayama H et al 2002 Bone Marrow Transplant. 29 197–204 10.1038/sj.bmt.1703356

Compassion fatigue in pediatric hematology, oncology, and bone marrow transplant healthcare providers: An integrative review

Objective Compassion fatigue (CF), which includes burnout and secondary traumatic stress, is highly prevalent among healthcare providers (HCPs). Ultimately, if left untreated, CF is often associated with absenteeism, decreased work performance, poor job satisfaction, and providers leaving their positions. To identify risk factors for developing CF and interventions to combat it in pediatric hematology, oncology, and bone marrow transplant (PHOB) HCPs. Methods An integrative review was conducted. Controlled vocabulary relevant to neoplasms, CF, pediatrics, and HCPs was used to search PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, and Web of Science MEDLINE. Inclusion criteria were the following: English language and PHOB population. Exclusion criteria were the following: did not address question, wrong study population, mixed study population where PHOB HCPs were only part of the population, articles about moral distress as this is a similar but not the same topic as CF, conference abstracts, and book chapters. Results A total of 16 articles were reviewed: 3 qualitative, 6 quantitative, 3 mixed methods, and 4 non research. Three themes were explored: (1) high-risk populations for developing CF, (2) sources of stress in PHOB HCPs, and (3) workplace interventions to decrease CF. Significance of results PHOB HCPs are at high risk of developing CF due to high morbidity and mortality in their patient population. Various interventions, including the use of a clinical support nurse, debriefing, support groups, respite rooms, and retreats, have varying degrees of efficacy to decrease CF in this population.