Background: Grenada is a small, resource‐limited Caribbean country with a high incidence of sickle cell disease (SCD). Since little is known about the challenges facing individuals living with SCD in the West Indies, we sought to assess barriers to healthcare and the impact of SCD on quality of life in Grenada.Methods: Both adults aged 18+ (n = 19) and caregivers of children aged 2–17 (n = 26) completed validated survey measures regarding barriers to care and quality of life, along with a genetics knowledge questionnaire. Caregivers also completed a caregiver burden scale. Survey scores were calculated, and responses were analyzed for an association between demographic variables.Results: The Barriers to Care Questionnaire, in which lower scores indicate more barriers, revealed that both adults (mean = 69.9) and children (mean = 75.5) with SCD experienced reduced access to care. The Adult Sickle Cell Quality of Life Measurement Information System indicated increased depression and loneliness in adults, with the lowest scores in the Emotional subscale. However, the Pediatric Quality of Life Inventory answered by caregivers of children with SCD showed the lowest scores in the Physical Functioning subscale. Further analysis using the Caregiver Burden Scale‐Zarit Burden Interview revealed that 53.8% of caregivers of children with SCD indicated “little to no burden,” which may reflect a difference in cultural expectations of a caregiver between high‐income countries and Grenada. Finally, ~80% of respondents knew that SCD was a genetic condition; however, 61%–84% could not correctly indicate recurrence risks, demonstrating a need for additional education.Conclusion: These data provide new insights regarding the experience of living with SCD in Grenada and support the need for further investigations into specific barriers to healthcare delivery, which could also improve education and well‐being for those affected by SCD in Grenada and in the broader Caribbean community.

Peptidyl-prolyl isomerase (PPIase) lipoproteins have been shown to influence the virulence of a number of Gram-positive bacterial human and animal pathogens, most likely through facilitating the folding of cell envelope and secreted virulence factors. Here, we used a proteomic approach to demonstrate that the Streptococcus equi PPIase SEQ0694 alters the production of multiple secreted proteins, including at least two putative virulence factors (FNE and IdeE2). We demonstrate also that, despite some unusual sequence features, recombinant SEQ0694 and its central parvulin domain are functional PPIases. These data add to our knowledge of the mechanisms by which lipoprotein PPIases contribute to the virulence of streptococcal pathogens.

Animal models of genetic disorders that have risen due to selective breeding can be used as a valuable model to teach the basic concepts of population genetics. The Clumber Spaniel is a breed of dog created in the mid-1700s by the 4th Duc du Noailles. He selectively bred this dog for the elderly gentleman. This sleepy-looking breed survives today, though 1% suffer from severe exercise intolerance due to an autosomal-recessive founder mutation in the pyruvate dehydrogenase phosphatase 1 (PDP1) gene. PDP1 deficiency was long suspected to be a human metabolic disorder and described at the molecular level in 2005 by Robinson and coworkers. The Robinson group later identified a founder mutation within the PDP1 gene of the Clumber spaniel. This case clearly illustrates how a detrimental mutant allele in a small population, when selecting for phenotype, can persist in the progeny of that group. In this review, we discuss the origin of the “Founder Effect” theory and present an example of how a bottleneck that occurred during the selective breeding of the Clumber spaniel over 250 years ago led to the current genetic status of the breed. Today, genotyping can help reduce the incidence of PDP1 in the Clumber breed.

Hemoglobinopathies such as sickle cell disease (SCD) and beta (β)-thalassemia are inherited disorders characterized by defective or insufficient β-globin chain production, resulting in chronic anemia, multi-organ damage, and reduced life expectancy. Affecting millions worldwide, particularly in sub-Saharan Africa, the Mediterranean, South Asia, the Middle East, and the Caribbean, these conditions represent the most common monogenic diseases globally. Traditional treatments, including blood transfusions and hydroxyurea, offer limited long-term benefit, while allogeneic bone marrow transplantation is curative but constrained by donor availability and procedural risks. In recent years, gene therapy and genome editing technologies have emerged as transformative tools, offering the potential for durable, patient-specific cures. This chapter reviews the underlying molecular mechanisms of SCD and β-thalassemia and explores current gene therapy approaches, including lentiviral gene addition and CRISPR-Cas9-mediated editing. A major focus is on reactivation of fetal hemoglobin (HbF) through targeted disruption of transcriptional repressors such as BCL11A. Clinical trial outcomes are examined alongside European Union (EU), United States of America (USA), and United Kingdom (UK) approved therapies such as Casgevy, Lyfgenia, and Zynteglo, highlighting both the therapeutic promise and real-world challenges, including myeloablative toxicity, access disparities, and infrastructure limitations. The chapter also emphasizes the global dimension of hemoglobinopathies and the urgent need for equitable implementation strategies, especially in resource-limited settings. Integrating insights from molecular genetics, clinical research, and global health policy, this chapter provides a comprehensive and up-to-date synthesis of genome editing advances and their application in curing SCD and β-thalassemia.

Sickle cell disease (SCD) is a monogenic hemoglobinopathy in which hemoglobin S (HbS) polymerizes on deoxygenation, leading to sickling of red blood cells (RBCs) and driving the acute vaso-occlusive crisis (VOC). With curative (transformative) therapies inaccessible to most patients in sub-Saharan Africa and the Caribbean, where burden is highest, optimizing acute VOC care is a priority; yet oxygen is given reactively, after hypoxemia is documented, not at symptom onset when polymerization is most interruptible. We conducted a structured narrative review integrating HbS polymerization kinetics, clinical studies of oxygen-based therapies, trial protocols, and home-care implementation evidence (PubMed, Scopus, Google Scholar; 1974–2026). When RBCs release oxygen, HbS does not solidify at once: a brief pause, the nucleation delay phase (t_D), precedes polymerization and sickling. Because t_D falls steeply as deoxygenated hemoglobin rises (inversely, to its ~30th–50th power), a small early gain in oxygen saturation (~5–10%) lengthens it many-fold, opening a short window, roughly 30 min from onset, during which oxygen may abort a crisis. The clinical message is that timing, not dose, is decisive: oxygen at the first symptoms may prevent a crisis that the same oxygen, given later, cannot. Standard, high-flow, hyperbaric, and inhaled nitric-oxide modalities help in selected hospital settings, and the DREPADOM model shows community delivery before hospital arrival is feasible and safe. The central argument is precision in timing, not quantity: starting oxygen at symptom onset could turn a low-cost, universally available treatment into a crisis-aborting one for patients beyond the reach of curative therapy. We advance this as a mechanistically grounded but clinically untested hypothesis; regional implementation trials in the Caribbean and sub-Saharan Africa are urgently warranted.