Gene therapy for sickle cell disease: recent advances, clinical trials and future directions.

Sickle cell disease (SCD) is the most common inherited blood disorder worldwide, impacting millions and imposing severe healthcare challenges, particularly in resource-limited regions. Current treatments have variable efficacy and require lifelong adherence. Allogeneic Hematopoietic Stem Cell Transplantation can be curative but comes with significant side effects and limited donor availability limits its widespread applicability.

"Change Isn't Exactly Easy": Autistic University Students' Lived Learning Experiences During the COVID-19 Pandemic.

Background: The COVID-19 (coronavirus disease 2019) pandemic-related isolation measures caused significant unexpected changes in learning experiences for all university students, including autistic students. So far, there has been a lack of information on autistic university students' lived learning experiences caused by the changes in the teaching delivery formats from face-to-face to online during this time. Our study addressed this gap by investigating eight autistic students' reported learning experiences during the rapid changes caused by the pandemic and discussing student-advocated learning supports.

Nucleated Red Blood Cells in Children With Sickle Cell Disease Hospitalized for Pain.

Acute chest syndrome (ACS) and transfusion requirements are common and difficult to predict during hospitalizations for acute vaso-occlusive episodes (VOE) among individuals with sickle cell disease (SCD). This study examined the relationship between nucleated red blood cell (NRBC) counts during hospitalization for VOE and development of ACS or transfusion requirement among children with SCD. Retrospective chart review was performed for 264 encounters of patients with SCD hospitalized for uncomplicated VOE who had NRBC count data at admission during a 5-year period.

Exploring the genomic basis of early childhood caries: a pilot study.

Objective: A genetic component in early childhood caries (ECC) is theorized, but no genome-wide investigations of ECC have been conducted. This pilot study is part of a long-term research program aimed to: (1) determine the proportion of ECC variance attributable to the human genome and (2) identify ECC-associated genetic loci.

Methods: The study's community-based sample comprised 212 children (mean age=39 months; range = 30-52 months; males = 55%; Hispanic/Latino = 35%, African-American = 32%; American Academy of Pediatric Dentistry definition of ECC prevalence = 38%).

RNA Trans-Splicing Targeting Endogenous β-Globin Pre-Messenger RNA in Human Erythroid Cells.

Sickle cell disease results from a point mutation in exon 1 of the β-globin gene (total 3 exons). Replacing sickle β-globin exon 1 (and exon 2) with a normal sequence by trans-splicing is a potential therapeutic strategy. Therefore, this study sought to develop trans-splicing targeting β-globin pre-messenger RNA among human erythroid cells.

Kinetics of lentiviral vector transduction in human CD34(+) cells.

Unlike cell lines, human hematopoietic stem cells (HSCs) are less efficiently transduced with HIV-1 vectors, potentially limiting this approach. To investigate which step (internalization, reverse transcription, nuclear transport, and integration) limits lentiviral transduction, we evaluated the kinetics of lentiviral transduction in human CD34(+) cells. We transduced HeLa and CD34(+) cells with self-inactivating HIV-1 vector at low and tenfold higher multiplicity of infection (MOI) and evaluated vector amounts at various time points based on the rationale that if a given step was not limiting, tenfold greater vector amounts would be obtained at the tenfold higher MOI.

Assessment of early occlusal caries pre- and post-sealant application--an imaging approach.

Background And Objective: Clinicians have difficulty assessing and monitoring early occlusal caries. Traditional clinical exam and radiographs are unable to detect the subtle alterations in enamel indicative of de- or re-mineralization, particularly under dental sealants. Although clinicians have used laser fluorescence (LF) to address this gap, this modality has demonstrated weak correlation with histology.

Early use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type 2 diabetes.

Objective: To evaluate the efficacy and safety of the available glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exenatide and liraglutide (marketed as Byetta * and Victoza † , respectively) in first- or second-line pharmacotherapy for type 2 diabetes (T2D), described here as 'early use'.

Research Design And Methods: MEDLINE, EMBASE and Google Scholar databases were queried for clinical trial reports using the terms incretin, GLP-1, exenatide and liraglutide. Relevant articles were those that employed these agents in treatment-naïve patients with T2D and in patients who had failed on metformin monotherapy.

Biomonitoring study of a group of workers potentially exposed to traffic fumes.

Risk assessment of environmental pollutants is concerned with the identification of compounds in the environment that might be hazardous to human health: measuring exposure levels, measuring cellular damage and then estimating the probability of harm occurring. The feasibility of such a comprehensive approach has been explored in this study of two groups of workers, one of which may be occupationally exposed to exhaust fumes. No statistically significant difference in cellular damage, as measured by the lymphocyte micronucleus assay, was found between these two groups of workers, although clear differences in exposure levels to volatile organic compounds were detected.

Lipids and oxidised lipids in human atherosclerotic lesions at different stages of development.

Lipids and oxidised lipids were analysed by GC and GC-MS in human necropsy samples of normal artery and individual atherosclerotic lesions, from aorta and common carotid artery, including fatty streaks, intermediate lesions and advanced lesions. Age-related increases were seen for linoleate, oleate and cholesterol in normal artery, but not in lesions. Each category of lesion was much richer than normal artery in all the lipids measured and in oxidised lipids (oxysterols and hydroxyoctadecadienoic acids), although a degree of overlap existed between the compositions of the various categories of lesion.

Production of oxidized lipids during modification of low-density lipoprotein by macrophages or copper.

The oxidation of low-density lipoprotein (LDL) is implicated in atherosclerosis. Lipids and oxidized lipids were analysed by gas chromatography and gas chromatography-mass spectrometry in human LDL incubated with mouse peritoneal macrophages (MPM) or copper (II) sulphate in Ham's F-10 medium or medium alone (control). MPM-modification and copper-catalysed oxidation of LDL resulted in the formation of oxysterols, mainly cholest-5-en-3 beta,7 beta-diol (7 beta-OH-CHOL); 7%-19% of the initial cholesterol was converted to 7 beta-OH-CHOL in 24 h.

Lipids and oxidised lipids in human atheroma and normal aorta.

Lipids and oxidised lipids were analysed by GC and GC-MS in samples of human atheroma (necrotic gruel from the interior of advanced atherosclerotic plaques in the aorta) and human normal aorta (lesion-free intima plus inner media) from necropsy subjects. Cholest-5-en-3 beta,26-diol and cholest-5-en-3 beta,7 beta-diol were detected in all the atheroma samples examined but not in significant amounts in normal aorta. In atheroma, cholest-5-en-3 beta,26-diol was approximately proportional to cholesterol.

Oxidation of cholesteryl linoleate by human monocyte-macrophages in vitro.

The amount of cholest-5-en-3 beta,7 beta-diol (CD) was significantly higher in cultures of human monocytes incubated with cholesteryl linoleate-bovine serum albumin (CL/BSA) artificial lipoproteins than in no-cell control incubations of CL/BSA. CD production by monocytes was almost completely inhibited by the radical scavengers butylated hydroxytoluene (BHT), probucol, and alpha-tocopherol, and was partially inhibited by the metal chelator EDTA. The production of CD was accompanied by decrease in linoleic acid.

The relationship of temperament and adjustment in Japanese schools.

We hypothesized that children whose temperaments match the features, demands, and values of their environment will demonstrate a better fit or adjustment to that environment. Culture is one factor that influences the environment. This study examined the temperament ideal held by Japanese teachers (N = 18) as well as the relationship between judged temperament and the adjustment of children (N = 108) in kindergarten, first-, and second-grade Japanese classrooms.

Polyadenylation of histone mRNA in Xenopus oocytes and embryos.

Oogenesis of amphibians is an atypical situation in which histone mRNA is polyadenylated. The poly(A) tract on H4 mRNA has been examined by S1 nuclease analysis. Throughout oogenesis the poly(A) tract is very short, and nonexistent on some mRNA molecules.

Are there major developmentally regulated H4 gene classes in Xenopus?

Primer extension analysis has been used to study the principal H4 mRNAs present at different developmental stages and in several adult tissues of Xenopus borealis and X. laevis. In X.

Organization and expression of cloned histone gene clusters from Xenopus laevis and X. borealis.

We have isolated several clones containing Xenopus histone genes from genomic libraries of X. laevis and X. borealis DNA.

Paternal gene expression in developing hybrid embryos of Xenopus laevis and Xenopus borealis.

We have studied protein synthesis in the viable hybrid Xenopus laevis (female) X Xenopus borealis (male) using 2D gel electrophoresis. Fourteen borealis-specific proteins were studied. Two of these proteins appeared by the gastrula stage, five in the gastrula and the rest later.

Actin synthesis during the early development of Xenopus laevis.

Cytoskeletal beta and gamma-actin are amongst the most rapidly made proteins of oocytes, blastulae and late embryonic stages of Xenopus laevis but, relative to other proteins, the rate of synthesis is low in the egg or cleaving embryo, although the messenger RNA is present in comparable amounts at the different stages. Actin synthesis therefore involves post-transcriptional regulation. alpha-Actin, the actin class characteristics of straited muscle cells, is first detectable in late gastrulae and it is an abundant newly synthetized protein from the neurula stage onwards.

The application of differential pulse voltammetry at the glassy carbon electrode to multivitamin analysis.

Differential pulse voltammetry at the glassy carbon electrode has been applied to the determination of ascorbic acid, pyridoxine and folic acid in a multivitamin preparation. The individual vitamins all gave well-defined peaks in the anodic region with a linear response of peak current to concentration. The water-soluble vitamins were extracted into aqueous solution and folic acid into dibasic potassium phosphate solution.

Changes in protein synthesis during the development of Xenopus laevis.

Patterns of protein synthesis during the development of Xenopus were studied by two-dimensional gel electrophoresis. Up to the end of the blastula stage we find no newly synthesized proteins which are not already made in the oocyte. The first new proteins are seen during gastrulation, and they increase in number during neurulation.

The determination of aluminium in antacid formulations by Gran's Plot titration with sodium fluoride.

The aluminium content of a number of proprietary antacid formulations has been determined by titration with sodium fluoride, using the fluoride activity electrode as an end-point detector. Results compared favourably with the official method. The fluoride titration, however, involved less sample manipulation and was more rapid to carry out.