What Would I Know About Mercy? Faith and Optimistic Expectancies Among African Americans

A small body of research has begun to explore the association between faith and optimism among African Americans. However, missing from the extant work is an examination of the extent to which traditional indices of religious commitment work together with beliefs about God to shape optimism. The present study examines the utility of indices of social location, religious commitment (i.e., early and current religious service attendance, subjective religiosity), belief about the quality of one’s relationship with God (i.e., a belief that one is connected to a loving God), and beliefs about being the recipient of divine forgiveness for predicting dispositional optimism among a sample of community residing African American adults (N = 241). Age, subjective religiosity, and organizational religiosity were positively related to optimism in bivariate analyses. Hierarchical regression analyses demonstrated a significant association between age, subjective religiosity, and optimism; however, those associations were eliminated once relationship with God and belief in one’s forgiveness by God were entered into the model. Only belief in God’s love predicted optimism in multivariate analyses. Serial mediation analyses revealed that beliefs about the quality of one’s relationship with God and belief in divine forgiveness fully mediated the relationship between subjective religiosity and optimism, but that the relationship is driven largely by relationship with God. Implications of these findings are discussed

OC 8510 BIOTRANSFORMATION OF PRAZIQUANTEL FOR THE PHARMACOKINETIC OPTIMISATION OF PRAZIQUANTEL USE IN MASS DRUG ADMINISTRATION AND DEVELOPMENT OF NEW PAEDIATRIC FORMULATIONS

BackgroundPraziquantel (PZQ) is the only drug available for the treatment of all forms of schistosomiasis. New paediatric formulations for the active enantiomer R-PZQ and the racemate PZQ are currently under development. There is however limited drug metabolism and pharmacokinetic data on PZQ available to support these initiatives. Detailed knowledge of PZQ metabolism will enable the use of PBPK modelling to determine appropriate doses for the new formulations in paediatric patients and to predict risks for drug-drug interactions in mass drug administration.MethodsBiotransformation studies on PZQ were conducted in human liver microsomes and recombinant Cytochrome P450s (CYPs). Structure elucidation was inferred from mass spectra. Enzyme kinetic studies to determine the Michaelis-Menten kinetics, Km and Vmax, of the formation of the main metabolites and analysis of clinical samples were determined by LC-MS/MS.ResultsCYP reaction phenotyping studies with HLM and r-CYPs indicate major involvement of CYP1A2, 2 C19, 2D6 and 3A4/5 in the metabolism of R- and S-PZQ. Biotransformation studies showed that PZQ is metabolised to cis-4-OH-PZQ mainly by CYP1A2 and CYP2C19. CYP3A4/5 metabolises PZQ to a mono-hydroxyl metabolite (X-OH-PZQ) whilst CYP2D6 metabolises PZQ to minor novel mono-hydroxyl metabolite (Y-OH-PZQ) both pending structural elucidation by nuclear magnetic resonance. R-PZQ was more rapidly cleared than S–PZQ with variable interindividual AUC and Cmax.Discussion and conclusionThe differential role of CYP1A2 and CYP2C19 and of CYP3A4 and CYP3A5 in the formation the 4-OH-PZQ and the novel X-OH-PZQ respectively are intriguing findings as this has not been reported before in humans. In vitro, cis and not trans 4-OH-PZQ formation has been observed contrary in vivo reports in humans which indicate trans 4-OH-PZQ as the main metabolite. The data will enable us to understand the rapid clearance of PZQ and predict potential drug-drug-gene interactions which mayexplain the inter-individual variability of PZQ pharmacokinetics

Improving Experiences of the Menopause for Women in Zimbabwe and South Africa:Co-Producing an Information Resource

Women in sub-Saharan Africa report multiple impacts of menopause on daily life and have requested further information to support themselves. This study co-produced contextually relevant resources—booklets and poster—about menopause with women in Zimbabwe and South Africa. The study was conducted in four stages: interviews with women about the menopause; the development of prototype information resources; workshops with women to discuss country-specific resources; and the refinement of resources. During the interviews, women explained that they had not received or accessed much information about the menopause and thought the physical and psychological issues associated with the menopause had to be “endured”. Prototype information resources comprised booklets and a poster with contextually relevant images and information. Workshop participants suggested several changes, including the addition of more diverse images and further information about treatments. The resources were refined, translated into several African languages, and endorsed by the Ministry of Health in Zimbabwe and the South African Menopause Society in South Africa. Women will be able to access resources through healthcare clinics, community groups and churches. Working with women and other stakeholders enabled a development that was cognisant of experiences and needs. Work is now needed to improve access to treatments and support for menopause to reduce health inequities

A comparison of collision cross section values obtained via travelling wave ion mobility-mass spectrometry and ultra high performance liquid chromatography-ion mobility-mass spectrometry : application to the characterisation of metabolites in rat urine

A comprehensive Collision Cross Section (CCS) library was obtained via Travelling Wave Ion Guide mobility measurements through direct infusion (DI). The library consists of CCS and Mass Spectral (MS) data in negative and positive ElectroSpray Ionisation (ESI) mode for 463 and 479 endogenous metabolites, respectively. For both ionisation modes combined, TWCCSN2 data were obtained for 542 non-redundant metabolites. These data were acquired on two different ion mobility enabled orthogonal acceleration QToF MS systems in two different laboratories, with the majority of the resulting TWCCSN2 values (from detected compounds) found to be within 1% of one another. Validation of these results against two independent, external TWCCSN2 data sources and predicted TWCCSN2 values indicated to be within 1-2% of these other values. The same metabolites were then analysed using a rapid reversed-phase ultra (high) performance liquid chromatographic (U(H)PLC) separation combined with IM and MS (IM-MS) thus providing retention time (tr), m/z and TWCCSN2 values (with the latter compared with the DI-IM-MS data). Analytes for which TWCCSN2 values were obtained by U(H)PLC-IM-MS showed good agreement with the results obtained from DI-IM-MS. The repeatability of the TWCCSN2 values obtained for these metabolites on the different ion mobility QToF systems, using either DI or LC, encouraged the further evaluation of the U(H)PLC-IM-MS approach via the analysis of samples of rat urine, from control and methotrexate-treated animals, in order to assess the potential of the approach for metabolite identification and profiling in metabolic phenotyping studies. Based on the database derived from the standards 63 metabolites were identified in rat urine, using positive ESI, based on the combination of tr, TWCCSN2 and MS data.</p

Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings

The Social Production of Altruism: Motivations for Caring Action in a Low-Income Urban Community

Contemporary social science paints a bleak picture of inner-city relational life. Indeed, the relationships of low-income, urban-residing Americans are represented as rife with distress, violence and family disruption. At present, no body of social scientific work systematically examines the factors that promote loving or selfless interactions among low-income, inner-city American individuals, families and communities. In an effort to fill that gap, this ethnographic study examined the motivations for altruism among a sample of adults (n = 40) who reside in an economically distressed housing community (i.e., housing project) in New York City. Content analyses of interviews indicated that participants attributed altruism to an interplay between 14 motives that were then ordered into four overarching categories of motives: (1) needs-centered motives, (2) norm-based motives deriving from religious/spiritual ideology, relationships and personal factors, (3) abstract motives (e.g., humanism), and (4) sociopolitical factors. The implications of these findings are discussed

High Throughput LC-MS Platform for Large Scale Screening of Bioactive Polar Lipids in Human Plasma and Serum

Lipids play a key role in many biological processes, and their accurate measurement is critical to unraveling the biology of diseases and human health. A high throughput HILIC-based (LC-MS) method for the semiquantitative screening of over 2000 lipids, based on over 4000 MRM transitions, was devised to produce an accessible and robust lipidomic screen for phospholipids in human plasma/serum. This methodology integrates many of the advantages of global lipid analysis with those of targeted approaches. Having used the method as an initial "wide class" screen, it can then be easily adapted for a more targeted analysis and quantification of key, dysregulated lipids. Robustness was assessed using 1550 continuous injections of plasma extracts onto a single column and via the evaluation of columns from 5 different batches of stationary phase. Initial screens in positive (239 lipids, 431 MRM transitions) and negative electrospray ionization (ESI) mode (232 lipids, 446 MRM transitions) were assessed for reproducibility, sensitivity, and dynamic range using analysis times of 8 min. The total number of lipids monitored using these screening methods was 433 with an overlap of 38 lipids in both modes. A polarity switching method for accurate quantification, using the same LC conditions, was assessed for intra- and interday reproducibility, accuracy, dynamic range, stability, carryover, dilution integrity, and matrix interferences and found to be acceptable. This polarity switching method was then applied to lipids important in the stratification of human prostate cancer samples