Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

T Cells Redirected to EphA2 for the Immunotherapy of Glioblastoma

Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.     

A prospective study of blood donations in healthy elderly persons

Iron stores were observed in 57 healthy elderly volunteers, between 63 and 77 years of age, who donated 5 units of blood over approximately 1 year. An equal number of nondonors who contributed approximately 7 mL of blood at each visit for iron status measurements only were seen at the same frequency as the donor population. At entrance to the study, iron stores in women and men averaged 724 and 875 mg, respectively. After five donations, mean iron stores dropped to 67 mg in women (n = 27) and 362 mg in men (n = 30); four women (15%) became iron deficient, while two (7%) developed iron deficiency anemia. Three men (10%) developed iron deficiency, but none were found to be anemic. Mean intakes of iron were 23.3 and 22.5 mg per day, respectively, for women and men. Iron intakes were adequate to meet iron requirements of nondonors, but they were not sufficient to halt the steady decrease in iron stores among the donor population, in whom iron absorption increased from approximately 5 percent at entrance to 14 percent at the time of the fifth donation. In summary, healthy elderly persons may contribute to the national blood resource; however, donations should probably be limited to less than five per year or donors should regularly take an iron supplement to preserve reasonable amounts of iron reserves.     

A comparison of the efficiency of surfactant contact lens cleaners in removing eyeliner adherent to various soft contact lenses

We compared the efficiency of removing cosmetic eyeliner deposits from soft contact lenses with a variety of surfactant cleaners. Four types of daily cleaners were used to clean two groups of soft contact lenses (Group 1 and Group 2 : FDA classification) contaminated with an eyeliner. The lenses were cleaned in a Clensatron 700CL Automatic Contact Lens Cleaning unit. The amount of lens contamination before and after cleaning was quantified by digitising a photograph of the lens surface. We found that: 1. the eyeliner was less likely to adhere to Group 2 lenses, 2. the efficiency of removing eyeliner was independent of the cleaning solutions we used; when contaminated, Group 2 lenses were generally easier to clean, 3. the Clensatron unit was not as efficient as digital rubbing in removing the eyeliner.     

Bilateral subacromial bursitis with macroscopic rice bodies: Ultrasound,CT and MR appearance

The radiological findings of ultrasound, CT and MR of a case of bilateral subacromial bursitis with macroscopic rice bodies is described. The previous literature is also reviewed.     

Reduced basal salivary cortisol in children with asthma and allergic rhinitis

Aim: Reduced basal cortisol is reported in allergic disease. We investigated if basal salivary cortisol levels were reduced in children with asthma or allergic rhinitis, controlling for inhaled corticosteroids (ICS) use. Methods: Morning and evening saliva of asthmatic children aged 7–12 years (n = 50) and that of controls (n = 52) were sampled. A total of 19 asthmatics and four controls had allergic rhinitis. Healthy children were controls without rhinitis. Of all, 14 asthmatic children used low, and 12 used moderate or high doses of ICS. Cortisol was analysed by radioimmunoassay. Results: Morning salivary cortisol median (95% CI) was lower in asthmatics (8.7 (7.1, 9.7)) compared with that in controls (10.4 (9.6, 11.8); p = 0.006), which was similar for evening cortisol levels. Regression analyses demonstrated that asthmatics using moderate or high doses of ICS had reduced morning salivary cortisol adjusted (for age and gender) odds ratio (aOR) (95% CI) (0.54 (0.37, 0.80); p = 0.002) and reduced evening cortisol aOR (0.09 (0.01, 0.6); p = 0.02) compared with that in healthy children. Asthmatics with rhinitis on no or low doses of ICS had reduced morning cortisol aOR (0.73 (0.56, 0.96); p = 0.02) compared with that in healthy children. Conclusion: Asthmatic children on moderate or high doses of inhaled corticosteroids had reduced salivary cortisol, but co‐morbidity of asthma and rhinitis was also associated with reduced cortisol levels.     

Knowledge and attitudes of infection prevention and control among health sciences students at University of Namibia

Background

Health Sciences students are exposed early to hospitals and to activities which increase their risk of acquiring infections. Infection control practices are geared towards reduction of occurrence and transmission of infectious diseases.

Objective

To evaluate knowledge and attitudes of infection prevention and control among Health Science students at University of Namibia.

Methods

To assess students'' knowledge and attitudes regarding infection prevention and control and their sources of information, a self-administered questionnaire was used to look at standard precautions especially hands hygiene.

Results

One hundred sixty two students participated in this study of which 31 were medical, 17 were radiography and 114 were nursing students. Medical students had better overall scores (73%) compared to nursing students (66%) and radiology students (61%). There was no significant difference in scores between sexes or location of the high school being either in rural or urban setting.

Conclusion

Serious efforts are needed to improve or review curriculum so that health sciences students'' knowledge on infection prevention and control is imparted early before they are introduced to the wards.