Skin flora and bacterial contamination of diversion pouch and recovered platelet components in Moroccan blood donors.

OBJECTIVE: The objective of this study was to evaluate bacterial reduction procedures used during whole-blood donations in Morocco. BACKGROUND: Bacterial contamination still poses serious challenges to blood safety, especially in countries with limited resources. METHODS: In the first part of this study, we analysed 233 swab samples taken from blood donors' antecubital fossa. After donation, a second batch of samples was analysed from the diversion pouches of corresponding donors. In addition, we searched for the prevalence of bacterial contamination in 568 randomly chosen platelet components at their expiration date in order to control for the entire blood unit preparation process. RESULTS: The most frequently found bacterial species at the antecubital fossa of healthy blood donors were coagulase-negative Staphylococcus, aerophilic Corynebacterium, Staphylococcus aureus, Bacillus sp. and Micrococcus sp. After donation, 5.15% of the diversion pouches were contaminated with bacterial species, the most notable being Bacillus sp., aerophilic Corynebacterium, coagulase-negative Staphylococcus, Staphylococcus aureus and Pseudomonas aeruginosa. Of 568 platelet components, 18 were contaminated with three bacterial species: Bacillus sp., coagulase-negative Staphylococcus and Staphylococcus aureus. CONCLUSION: All three bacterial species found in platelet components were detected on the skin of blood donors. Serious measures need to be taken and enforced to ensure blood safety.

H3ABioNet, a sustainable pan-African bioinformatics network for human heredity and health in Africa.

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.

Determinants of severe oral mucositis in paediatric cancer patients: a prospective study.

OBJECTIVE: To analyse the incidence and the determinants of severe oral mucositis (OM) in young cancer patients treated by standard chemotherapy. METHODS: The study was carried out at the Pediatric Hemato-Oncology unit of Children's Hospital of Rabat. Patients under 16 years of age with malignant disease treated by chemotherapy between January 2001 and December 2006 were recorded. RESULTS: Consecutive patients (n = 970) with malignant disease were studied. The age ranges from 2 months to 16 years (mean, 6.8 ± 4.1 years). OM occurred in 540 (55.6%) patients, and 17.9% of them encountered severe grades. Mean time to onset of the lesions was 10.5 ± 6.8 (range, 1-22 days) and mean duration was 6.8 ± 3.1 (range, 2-23 days). All chemotherapeutic protocols were associated with OM development (range, 20-100%). Patients with severe OM were more likely to have undifferentiated carcinoma of nasopharyngeal type (RR = 2.6, 95% IC 1.1-6.1), non-Hodgkin lymphoma (RR = 2.1, 95% CI 1.2-2.4) and acute leukaemia (RR = 1.7, 95% CI 1.5-3.6). Methotrexate-based therapies were also associated with the worsening of OM (RR = 1.7, 95% IC 1.2-2.6). CONCLUSION: Underlying disease and chemotherapy regimens are the principal risk factors of OM development. This model can help in the identification of patients at risk for adequate preventive and therapeutic measures.

HbS-Savaria: the anti-polymerization effect of a single mutation in human alpha-chains.

Recombinant alpha-Savaria globin (alpha(S49R)) was assembled with beta(S) chains by the alloplex intermediate pathway to generate tetrameric rHbS-Sarvaria (alpha (2) (S49R) beta (2) (E6V) ) that exhibited normal O(2) affinity and co-operatively at pH 7.4. Allosteric effectors, 2,3-DPG, L35, and NaCl increased O(2) affinity by 15%. Bohr effects were similar for rHbS-Savaria and HbS (0.38 +/- 0.025 vs. 0.46 +/- 0.03, respectively). The C(SAT) of HbS increased from 16.7 +/- 0.8 to 27.0 +/- 1.0 g/dL. Co-polymerization demonstrated inhibition predominantly by the Cis-dimer. Molecular modeling indicated that the positive charge at alpha-49 generated a strong anion-binding site and reduced flexibility of the CD-region by restricting movement in the E and F helices. The molecular distance between Arg-49 and Asn-78 in the neighboring double strand decreased, and electrostatic repulsion between the inter-double strands increased, resulting in inhibition of polymerization. The Savaria mutation may be useful for the design of super-inhibitory alpha-chains and gene therapy of sickle cell anemia.

Pair-wise interactions of polymerization inhibitory contact site mutations of hemoglobin-S.

The linkage of pair-wise interactions of contact site mutations of HbS has been studied using Le Lamentin [His-20 (alpha)-->Gln], Hoshida [Glu-43 (beta)-->Gln] and alpha(2)beta (2) (T87Q) mutations as the prototype of three distinct classes of contact sites of deoxy HbS fiber. Binary mixture experiments established that beta(A)-chain with the Thr-87 (beta)-->Gln mutation is as potent as the gamma-chain of HbF (alpha(2)gamma(2)) in inhibiting polymerization. On combining the influence of Le Lamentin mutation with that of beta (2) (T87Q) mutations; the net influence is only partial additivity. On the other hand, in binary mixture studies, combined influence of Hoshida mutation with that of beta (2) (T87Q) mutations is synergistic. Besides, a significant level of synergistic complementation is also seen when the Le Lamentin and Hoshida mutations are combined in HbS (symmetrical tetramers). Le Lamentin and Hoshida mutation introduced into the cis-dimer of the asymmetric hybrid tetramer completely neutralizes the Val-6 (beta) dependent polymerization. Accordingly, we propose that combining the perturbation of intra-double strand contact site with that of an inter-double strand contact site exhibit synergy when they are present in two different chains of the alphabeta dimer. A comparison of the present results with that of the earlier studies suggest that when the two contact site perturbations are from the same sub-unit of the alphabeta dimer only partial additivity is observed. The map of interaction linkage of the contact site mutations exposes new strategies in the design of novel anti-sickling Hbs for the gene therapy of sickle cell disease.

Mammalian linker-histone subtypes differentially affect gene expression in vivo.

Posttranslational modifications and remodeling of nucleosomes are critical factors in the regulation of transcription. Higher-order folding of chromatin also is likely to contribute to the control of gene expression, but the absence of a detailed description of the structure of the chromatin fiber has impaired progress in this area. Mammalian somatic cells contain a set of H1 linker-histone subtypes, H1 (0) and H1a to H1e, that bind to nucleosome core particles and to the linker DNA between nucleosomes. To determine whether the H1 histone subtypes play differential roles in the regulation of gene expression, we combined mice lacking specific H1 histone subtypes with mice carrying transgenes subject to position effects. Because position effects result from the unique chromatin structure created by the juxtaposition of regulatory elements in the transgene and at the site of integration, transgenes can serve as exquisitely sensitive indicators of chromatin structure. We report that some, but not all, linker histones can attenuate or accentuate position effects. The results suggest that the linker-histone subtypes play differential roles in the control of gene expression and that the sequential arrangement of the linker histones on the chromatin fiber might regulate higher-order chromatin structure and fine-tune expression levels.