Evaluation of Traditional Medicines II: The Use of Metabolite Peak-Kinetics to Monitor PHELA in Rat Plasma.

PHELA is a herbal mixture of four African traditional medicinal plants that is under development by the Medical Research Council (MRC) for use as an immune stimulant in immune compromised individuals. Before major in vivo investigations could be conducted, there was a need to establish a plasma marker for concentration monitoring of PHELA. Chromatographic separation was achieved using a C18 RP column (250 mm x 4.6 mm x 5 μm), 70% acetonitrile in water and fluorescent detection. Three groups of rats (n=5) were administered with PHELA (15.4 mg/kg) and one rat from each group was sacrificed at 1, 2, 4, 6 and 8 hours. Surprisingly, on the HPLC analysis, none of the marker peaks of spiked plasma were detectable in the plasma of treated animals. Instead, a new peak was observed at 9.2 minutes, which implied that it was a metabolite of PHELA. Using peak area per unit plasma volume (PK-area/L), the relevant pharmacokinetic parameters were derived. The metabolite’s half-life was 3.47±0.35 hours and reached maximum concentration at 4.67 ± 1.15 hrs. It was estimated that with once daily dosing of PHELA, the concentration at steady state (Css) would be 47.52 ± 5.94 PK-area/L with no drug accumulation (Acc index =.009 ± 0.004). In conclusion, the use of peak area per unit volume to derive pharmacokinetics of unknown compounds (Peak-kinetics) and to confirm ingestion of PHELA were demonstrated with a hope that they may appeal to those experiencing similar problems with monitoring of herbal products of which little is known.Key words: PHELA, Herbal medicine, Peak-kinetics, plasma, HPLC metho

Evaluation of Traditional Medicines III: The Mechanism of Immune Modulation by PHELA.

PHELA is a herbal traditional medicine that is under development for use as an immune booster in immune compromised individuals. Therefore, the aim of this study was to determine PHELA’s mechanism of action by observing for changes in cytokine profiles. Four groups of Sprague Dawley rats (n = 8) were treated daily and separately with normal-saline, cyclosporine-A, PHELA-only and PHELA+ cyclosporine-A. Thereafter, 4 animals from each group were sacrificed after 7 and 14 days of treatment. Serum Th1 cytokines (IL-2, IFN-γ and TNF-ά) and Th2 cytokines (IL-4 and IL-10) were measured by ELISA. The concentrations of Th1 cytokines in the PHELA-only treated group were similar to the control group on days 7 and 14. However, the Th1 cytokines were higher in the PHELA+cyclosporine-A treated group compared to cyclosporine-A group, and cyclosporine-A concentrations were similar in both groups. These results show that PHELA did not stimulate Th1 cytokines of a normal immune system but stimulated them when the immune system was suppressed by cyclosporine-A. In conclusion, PHELA is an immune-stimulant to a compromised immune system.Key words: PHELA, traditional medicine, cyclosporine-A, cytokines, immune stimulan

Nutritional status of renal transplant patients

Objective. To assess the effect of renal transplantation on the nutritional status of patients.Design. Prospective descriptive study.Setting. Renal Transplant Clinic at Tygerberg Hospital, Western Cape.Subjects. Fifty-eight renal transplant patients from Tygerberg Hospital were enrolled in the study. The sample was divided into two groups of 29 patients each: group 1, less than 28 months post-transplant; and group 2, more than 28 months post-transplant.Outcome measures. Nutritional status assessment comprised biochemical evaluation, a dietary history, anthropometric measurements and a clinical examination.Results. Serum vitamin B6 levels were below normal in 56% of patients from group 1 and 59% from group 2. Vitamin B6 intake, however, was insufficient in only 14% of patients from group 1and10% from group 2. Serum vitamin C levels were below normal in 7% of patients from group 1 and 24% from group 2, while vitamin C intake was insufficient in 21%and14% of patients from groups 1 and 2 respectively. Serum magnesium levels were below normal in 55% of patients from group 1, and in 28% from group 2. Serum albumin and cholesterol levels increased significantly during the post-transplant period in the total sample (P = 0.0001). There was also a significant increase in body mass index (P = 0.0001) during the post-transplant period.Conclusions. Several nutritional abnormalities were observed, which primarily reflect the side-effects of immunosuppressive therapy. The causes, consequences and treatment of the vitamin B6 and vitamin C deficiencies in renal transplant recipients need further investigation

Effects of the Insemination of Hydrogen Peroxide-Treated Epididymal Mouse Spermatozoa on γH2AX Repair and Embryo Development

BACKGROUND: Cryopreservation of human semen for assisted reproduction is complicated by cryodamage to spermatozoa caused by excessive reactive oxygen species (ROS) generation. METHODS AND FINDINGS: We used exogenous ROS (H(2)O(2)) to simulate cryopreservation and examined DNA damage repair in embryos fertilized with sperm with H(2)O(2)-induced DNA damage. Sperm samples were collected from epididymis of adult male KM mice and treated with capacitation medium (containing 0, 0.1, 0.5 and 1 mM H(2)O(2)) or cryopreservation. The model of DNA-damaged sperm was based on sperm motility, viability and the expression of γH2AX, the DNA damage-repair marker. We examined fertility rate, development, cell cleavage, and γH2AX level in embryos fertilized with DNA-damaged sperm. Cryopreservation and 1-mM H(2)O(2) treatment produced similar DNA damage. Most of the one- and two-cell embryos fertilized with DNA-damaged sperm showed a delay in cleavage before the blastocyst stage. Immunocytochemistry revealed γH2AX in the one- and four-cell embryos. CONCLUSIONS: γH2AX may be involved in repair of preimplantation embryos fertilized with oxygen-stressed spermatozoa

The influence of refuge sharing on social behaviour in the lizard Tiliqua rugosa

Refuge sharing by otherwise solitary individuals during periods of inactivity is an integral part of social behaviour and has been suggested to be the precursor to more complex social behaviour. We compared social association patterns of active versus inactive sheltering individuals in the social Australian sleepy lizard, Tiliqua rugosa, to empirically test the hypothesis that refuge sharing facilitates social associations while individuals are active. We fitted 18 neighbouring lizards with Global Positioning System (GPS) recorders to continuously monitor social associations among all individuals, based on location records taken every 10 min for 3 months. Based on these spatial data, we constructed three weighted, undirected social networks. Two networks were based on empirical association data (one for active and one for inactive lizards in their refuges), and a third null model network was based on hypothetical random refuge sharing. We found patterns opposite to the predictions of our hypothesis. Most importantly, association strength was higher in active than in inactive sheltering lizards. That is, individual lizards were more likely to associate with other lizards while active than while inactive and in shelters. Thus, refuge sharing did not lead to increased frequencies of social associations while lizards were active, and we did not find any evidence that refuge sharing was a precursor to sleepy lizard social behaviour. Our study of an unusually social reptile provides both quantitative data on the relationship between refuge sharing and social associations during periods of activity and further insights into the evolution of social behaviour in vertebrates

Subject specific demands of teaching: Implications for out-of-field teachers

This chapter provides a framework for thinking about the subject-specific nature of teaching in terms of the knowledge, modes of inquiry and discursive practices that delineate one subject from another in the traditional school curriculum. The chapter will explore how these disciplinary traits are translated into teaching as curriculum, knowledge and pedagogy, and how this subject-specificity of teaching is juxtaposed against the more generic aspects of teaching. The chapter explores the idea that if a teacher’s expertise can be situated within a field, then they can also be positioned out-of-field. Implications for teaching out-of-field are discussed in terms of the subject-specific knowledge, processes and skills, and the difficulties associated with teacher practice. English and Australian illustrations of teacher practices from in-field and out-of-field situations are provided, in particular highlighting the demands of moving across subject boundaries. Cross-fertilisation is especially evident when subjects are integrated, therefore, the issues associated with integrated curriculum are discussed where the traditional subject boundaries are being challenged as schools are reorganised to integrate subjects through, for example, STEM teaching, or holistic curriculum designs

Phase-specific and lifetime costs of cancer care in Ontario, Canada

BACKGROUND: Cancer is a major public health issue and represents a significant economic burden to health care systems worldwide. The objective of this analysis was to estimate phase-specific, 5-year and lifetime net costs for the 21 most prevalent cancer sites, and remaining tumour sites combined, in Ontario, Canada. METHODS: We selected all adult patients diagnosed with a primary cancer between 1997 and 2007, with valid ICD-O site and histology codes, and who survived 30 days or more after diagnosis, from the Ontario Cancer Registry (N = 394,092). Patients were linked to treatment data from Cancer Care Ontario and administrative health care databases at the Institute for Clinical and Evaluative Sciences. Net costs (i.e., cost difference between patients and matched non-cancer control subjects) were estimated by phase of care and sex, and used to estimate 5-year and lifetime costs. RESULTS: Mean net costs of care (2009 CAD) were highest in the initial (6 months post-diagnosis) and terminal (12 months pre-death) phases, and lowest in the (3 months) pre-diagnosis and continuing phases of care. Phase-specific net costs were generally lowest for melanoma and highest for brain cancer. Mean 5-year net costs varied from less than $25,000 for melanoma, thyroid and testicular cancers to more than$60,000 for multiple myeloma and leukemia. Lifetime costs ranged from less than $55,000 for lung and liver cancers to over$110,000 for leukemia, multiple myeloma, lymphoma and breast cancer. CONCLUSIONS: Costs of cancer care are substantial and vary by cancer site, phase of care and time horizon analyzed. These cost estimates are valuable to decision makers to understand the economic burden of cancer care and may be useful inputs to researchers undertaking cancer-related economic evaluations

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

The evolutionary signal in metagenome phyletic profiles predicts many gene functions

Background. The function of many genes is still not known even in model organisms. An increasing availability of microbiome DNA sequencing data provides an opportunity to infer gene function in a systematic manner. Results. We evaluated if the evolutionary signal contained in metagenome phyletic profiles (MPP) is predictive of a broad array of gene functions. The MPPs are an encoding of environmental DNA sequencing data that consists of relative abundances of gene families across metagenomes. We find that such MPPs can accurately predict 826 Gene Ontology functional categories, while drawing on human gut microbiomes, ocean metagenomes, and DNA sequences from various other engineered and natural environments. Overall, in this task, the MPPs are highly accurate, and moreover they provide coverage for a set of Gene Ontology terms largely complementary to standard phylogenetic profiles, derived from fully sequenced genomes. We also find that metagenomes approximated from taxon relative abundance obtained via 16S rRNA gene sequencing may provide surprisingly useful predictive models. Crucially, the MPPs derived from different types of environments can infer distinct, non-overlapping sets of gene functions and therefore complement each other. Consistently, simulations on > 5000 metagenomes indicate that the amount of data is not in itself critical for maximizing predictive accuracy, while the diversity of sampled environments appears to be the critical factor for obtaining robust models. Conclusions. In past work, metagenomics has provided invaluable insight into ecology of various habitats, into diversity of microbial life and also into human health and disease mechanisms. We propose that environmental DNA sequencing additionally constitutes a useful tool to predict biological roles of genes, yielding inferences out of reach for existing comparative genomics approaches

Global landscape review of serotype-specific invasive pneumococcal disease surveillance among countries using PCV10/13: The pneumococcal serotype replacement and distribution estimation (PSERENADE) project

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon