Surgical Patients\' Knowledge and Acceptance of Autologous Blood Transfusion.

Background: Homologous blood transfusion carries a well-documented array of risks especially in an HIV endemic environment like Nigeria. It is therefore imperative to consider other forms of restoring blood volume in surgical patients. Autologous blood transfusion (ABT) is one of the ways the problem of HIV transmission can be reduced among surgical patients. The knowledge and acceptability of ABT among surgical patients about ABT, especially pre-donated ABT were assessed. It also assessed whether or not surgeons inform elective surgical patients about this alternative Materials And Methods Questionnaires were distributed among elective surgical patients that presented during the study period. The knowledge, willingness and the factors influencing the willingness of the patients to participate in ABT were investigated. The data were analyzed with SPSS Version10. Results Of the 116 patients [71 males; 45 females] interviewed, 29 (25.0 %) had heard about ABT, 80 (69.0 %) patients had never heard about ABT while 7 (6.1 %) were not sure. Of the 29 respondents who had heard about ABT, only 2 had had ABT. Of the 48 patients who needed blood for current surgical problems, only 4 (9.3 %) would have ABT. There was a significant difference in the number of respondents who believed that ABT is better than homologous transfusion (x2 = 69.11, p < 0.001). Conclusion The knowledge of ABT is low among our surgical patients and surgeons should present this alternative to their patients. The acceptance of ABT may also help in reducing or eliminating HIV transmission via blood transfusion. Keywords: homologous, hepatitis, surgical procedures, blood volume.Sudan Journal of Medical Sciences Vol. 3 (2) 2008: pp. 109-11

Synergistic Anticancer Effects of the 9.2.27PE Immunotoxin and ABT-737 in Melanoma

In cancer, combinations of drugs targeting different cellular functions is well accepted to improve tumor control. We studied the effects of a Pseudomonas exotoxin A (PE) - based immunotoxin, the 9.2.27PE, and the BH-3 mimetic compound ABT-737 in a panel of melanoma cell lines. The drug combination resulted in synergistic cytotoxicity, and the cell death observed was associated with apoptosis, as activation of caspase-3, inactivation of Poly (ADP-ribose) polymerase (PARP) and increased DNA fragmentation could be prevented by pre-treatment with caspase and cathepsin inhibitors. We further show that ABT-737 caused endoplasmic reticulum (ER) stress with increased GRP78 and phosphorylated eIF2α protein levels. Moreover, treatment with ABT-737 increased the intracellular calcium levels, an effect which was enhanced by 9.2.27PE, which as a single entity drug had minimal effect on calcium release from the ER. In addition, silencing of Mcl-1 by short hairpin RNA (shRNA) enhanced the intracellular calcium levels and cytotoxicity caused by ABT-737. Notably, the combination of 9.2.27PE and ABT-737 caused growth delay in a human melanoma xenograft mice model, supporting further investigations of this particular drug combination

Advances in the Analytical Methods for Determining the Antioxidant Properties of Honey: A Review

Free radicals and reactive oxygen species (ROS) have been implicated in contributing to the processes of aging and disease. In an effort to combat free radical activity, scientists are studying the effects of increasing individuals' antioxidant levels through diet and dietary supplements. Honey appears to act as an antioxidant in more ways than one. In the body, honey can mop up free radicals and contribute to better health. Various antioxidant activity methods have been used to measure and compare the antioxidant activity of honey. In recent years, DPPH (Diphenyl-1-picrylhydrazyl), FRAP (Ferric Reducing Antioxidant Power), ORAC (The Oxygen Radical Absorbance Capacity), ABTS [2, 2-azinobis (3-ehtylbenzothiazoline-6-sulfonic acid) diamonium salt], TEAC [6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acid (Trolox)-equivalent antioxidant capacity] assays have been used to evaluate antioxidant activity of honey. The antioxidant activity of honey is also measured by ascorbic acid content and different enzyme assays like Catalase (CAT), Glutathione Peroxidase (GPO), Superoxide Dismutase (SOD). Among the different methods available, methods that have been validated, standardized and widely reported are recommended.Key words: Honey; antioxidant properties; DPPH; FRAP; ORAC; TEAC; ABT

Complementary Metagenomic Approaches Improve Reconstruction of Microbial Diversity in a Forest Soil.

Soil ecosystems harbor diverse microorganisms and yet remain only partially characterized as neither single-cell sequencing nor whole-community sequencing offers a complete picture of these complex communities. Thus, the genetic and metabolic potential of this "uncultivated majority" remains underexplored. To address these challenges, we applied a pooled-cell-sorting-based mini-metagenomics approach and compared the results to bulk metagenomics. Informatic binning of these data produced 200 mini-metagenome assembled genomes (sorted-MAGs) and 29 bulk metagenome assembled genomes (MAGs). The sorted and bulk MAGs increased the known phylogenetic diversity of soil taxa by 7.2% with respect to the Joint Genome Institute IMG/M database and showed clade-specific sequence recruitment patterns across diverse terrestrial soil metagenomes. Additionally, sorted-MAGs expanded the rare biosphere not captured through MAGs from bulk sequences, exemplified through phylogenetic and functional analyses of members of the phylum Bacteroidetes Analysis of 67 Bacteroidetes sorted-MAGs showed conserved patterns of carbon metabolism across four clades. These results indicate that mini-metagenomics enables genome-resolved investigation of predicted metabolism and demonstrates the utility of combining metagenomics methods to tap into the diversity of heterogeneous microbial assemblages.IMPORTANCE Microbial ecologists have historically used cultivation-based approaches as well as amplicon sequencing and shotgun metagenomics to characterize microbial diversity in soil. However, challenges persist in the study of microbial diversity, including the recalcitrance of the majority of microorganisms to laboratory cultivation and limited sequence assembly from highly complex samples. The uncultivated majority thus remains a reservoir of untapped genetic diversity. To address some of the challenges associated with bulk metagenomics as well as low throughput of single-cell genomics, we applied flow cytometry-enabled mini-metagenomics to capture expanded microbial diversity from forest soil and compare it to soil bulk metagenomics. Our resulting data from this pooled-cell sorting approach combined with bulk metagenomics revealed increased phylogenetic diversity through novel soil taxa and rare biosphere members. In-depth analysis of genomes within the highly represented Bacteroidetes phylum provided insights into conserved and clade-specific patterns of carbon metabolism

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Mapping environmental injustices: pitfalls and potential of geographic information systems in assessing environmental health and equity.

Geographic Information Systems (GIS) have been used increasingly to map instances of environmental injustice, the disproportionate exposure of certain populations to environmental hazards. Some of the technical and analytic difficulties of mapping environmental injustice are outlined in this article, along with suggestions for using GIS to better assess and predict environmental health and equity. I examine 13 GIS-based environmental equity studies conducted within the past decade and use a study of noxious land use locations in the Bronx, New York, to illustrate and evaluate the differences in two common methods of determining exposure extent and the characteristics of proximate populations. Unresolved issues in mapping environmental equity and health include lack of comprehensive hazards databases; the inadequacy of current exposure indices; the need to develop realistic methodologies for determining the geographic extent of exposure and the characteristics of the affected populations; and the paucity and insufficiency of health assessment data. GIS have great potential to help us understand the spatial relationship between pollution and health. Refinements in exposure indices; the use of dispersion modeling and advanced proximity analysis; the application of neighborhood-scale analysis; and the consideration of other factors such as zoning and planning policies will enable more conclusive findings. The environmental equity studies reviewed in this article found a disproportionate environmental burden based on race and/or income. It is critical now to demonstrate correspondence between environmental burdens and adverse health impacts--to show the disproportionate effects of pollution rather than just the disproportionate distribution of pollution sources

Social Aspects of Malaria among Students in Two Tertiary Institutions in Lagos, Nigeria

Studies were carried out on the social aspects of malaria among 600 students. Three hundred students (150 male, 150 females) were randomly selected from two tertiary institutions in Lagos, Nigeria. These schools are Lagos State University (LASU) and AOCOED (Adeniran Ogunsanya College of Education). A structured questionnaire elicited relevant information on knowledge, perception and social aspects of malaria. Students aged 21-23, from faculty of arts and in their second year participated mostly in the study with no significant difference between the two schools. In LASU, 223(74.3%) and 211(70.3%) in AOCOED knew the cause of malaria (P&gt;0.05). In LASU, 282(94%) and 192(64%) in AOCOED believed that malaria could be prevented (P&lt;0.05). In LASU, 283(96%) and 283(94.3%) in AOCOED believed malaria could be treated (P&gt;0.05). 109 (36.3%) respondents in LASU and 112(37.3%) in AOCOED thought that malaria was contagious (P&gt;0.05). Fever was the most recognised symptom of malaria in both schools and self-medication was more popular in AOCOED. In LASU, 284(94.6%) and AOCOED, 273(91%) had malaria in the past one year (P&gt;0.05). 146(48.7%) of the students who participated in LASU and 206(68.6%) in AOCOED had been admitted for malaria within the past one year (P&lt;0.05). Class absenteeism and low academic performance were significantly higher in AOCOED than LASU. However, our results suggested that the LASU students were more informed about malaria than the AOCOED students because their knowledge and perception was better. The students, despite their academic backgrounds need intensified health education on malaria incorporated into their schools&rsquo; curriculum.Keywords: Academic performance, Knowledge and perception, Malaria, Socioeconomic status, Student

Novel Binding Mode of a Potent and Selective Tankyrase Inhibitor

Tankyrases (TNKS1 and TNKS2) are key regulators of cellular processes such as telomere pathway and Wnt signaling. IWRs (inhibitors of Wnt response) have recently been identified as potent and selective inhibitors of tankyrases. However, it is not clear how these IWRs interact with tankyrases. Here we report the crystal structure of the catalytic domain of human TNKS1 in complex with IWR2, which reveals a novel binding site for tankyrase inhibitors. The TNKS1/IWR2 complex provides a molecular basis for their strong and specific interactions and suggests clues for further development of tankyrase inhibitors

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context