Counternarratives from Women of Color Academics: Bravery, Vulnerablility and Resistance

This book documents the lived experiences of women of color academics who have leveraged their professional positions to challenge the status quo in their scholarship, teaching, service, activism, and leadership. By presenting reflexive work from various vantage points within and outside of the academy, contributors document the cultivation of mentoring relationships, the use of administrative roles to challenge institutional leadership, and more. Through an emphasis on the various ways in which women of color have succeeded in the academy—albeit with setbacks along the way—this volume aims to change the discourse surrounding women of color academics: from a focus on trauma and mere survival to a focus on courage and thriving.https://scholarship.richmond.edu/bookshelf/1311/thumbnail.jp

A Toolkit to assess health needs for congenital disorders in low- and middle-income countries: an instrument for public health action.

BACKGROUND: In 2010 the World Health Assembly called for action to improve the care and prevention of congenital disorders, noting that technical guidance would be required for this task, especially in low- and middle-income countries. Responding to this call, we have developed a freely available web-accessible Toolkit for assessing health needs for congenital disorders. METHODS: Materials for the Toolkit website (http://toolkit.phgfoundation.org) were prepared by an iterative process of writing, discussion and modification by the project team, with advice from external experts. A customized database was developed using epidemiological, demographic, socio-economic and health-services data from a range of validated sources. Document-processing and data integration software combines data from the database with a template to generate topic- and country-specific Calculator documents for quantitative analysis. RESULTS: The Toolkit guides users through selection of topics (including both clinical conditions and relevant health services), assembly and evaluation of qualitative and quantitative information, assessment of the potential effects of selected interventions, and planning and prioritization of actions to reduce the risk or prevalence of congenital disorders. CONCLUSIONS: The Toolkit enables users without epidemiological or public health expertise to undertake health needs assessment as a prerequisite for strategic planning in relation to congenital disorders in their country or region

Neonatal mortality in NHS maternity units by timing and mode of birth: a retrospective linked cohort study

OBJECTIVES: To compare neonatal mortality in English hospitals by time of day and day of the week according to care pathway. DESIGN: Retrospective cohort linking birth registration, birth notification and hospital episode data. SETTING: National Health Service (NHS) hospitals in England. PARTICIPANTS: 6 054 536 liveborn singleton births from 2005 to 2014 in NHS maternity units in England. MAIN OUTCOME MEASURES: Neonatal mortality. RESULTS: After adjustment for confounders, there was no significant difference in the odds of neonatal mortality attributed to asphyxia, anoxia or trauma outside of working hours compared with working hours for spontaneous births or instrumental births. Stratification of emergency caesareans by onset of labour showed no difference in mortality by birth timing for emergency caesareans with spontaneous or induced onset of labour. Higher odds of neonatal mortality attributed to asphyxia, anoxia or trauma out of hours for emergency caesareans without labour translated to a small absolute difference in mortality risk. CONCLUSIONS: The apparent 'weekend effect' may result from deaths among the relatively small numbers of babies who were coded as born by emergency caesarean section without labour outside normal working hours. Further research should investigate the potential contribution of care-seeking and community-based factors as well as the adequacy of staffing for managing these relatively unusual emergencies

Is aristolochic acid nephropathy a widespread problem in developing countries? A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical - phytochemical approach

Ethnopharmacological relevance: Species of Aristolochia are associated with aristolochic acid nephropathy (AAN), a renal interstitial fibrosis and upper urinary tract cancer (UUC). Aristolochic acid nephropathy has been reported in ten countries but its true incidence is unknown and most likely underestimated. By combining an ethnobotanical and phytochemical approach we provide evidence for the risk of AAN occurring in Bangladesh. More specifically, we assess the intra-specific variation of aristolochic acid analogues in medicinally used A. indica samples from Bangladesh. Materials and Methods: Ethnobotanical information was collected from 16 kavirajes (traditional healers) in different study locations in Bangladesh. Plant samples were obtained from native habitats, botanical gardens, herbal markets and pharmaceutical companies. The samples were extracted using 70% methanol and were analysed using LC-DAD-MS and 1H-NMR. Results: Roots as well as leaves are commonly used for symptoms such as snake bites and sexual problems. Among the informants knowledge about toxicity or side effects is very limited and A. indica is often administered in very high doses. Replacement of A. indica with other medicinal plants such as Rauvolfia serpentina (L.) Benth. ex Kurz was common. A. indica samples contained a variety of aristolochic acid analogues such as aristolochic acid I, aristolochic acid II, cepharadione A and related compounds. Conclusions: AAN cases are likely to occur in Bangladesh and more awareness needs to be raised about the health risks associated with the use of A. indica and other species of Aristolochia as herbal medicines

Maternity service reconfigurations for intrapartum and postnatal midwifery staffing shortages: modelling of low-risk births in England

Introduction Choice of birth setting is important and it is valuable to know how reconfiguring available settings may affect midwifery staffing needs. COVID-19-related health system pressures have meant restriction of community births. We aimed to model the potential of service reconfigurations to offset midwifery staffing shortages. Methods We adapted the Birthrate Plus method to develop a tool that models the effects on intrapartum and postnatal midwifery staffing requirements of changing service configurations for low-risk births. We tested our tool on two hypothetical model trusts with different baseline configurations of hospital and community low-risk birth services, representing those most common in England, and applied it to scenarios with midwifery staffing shortages of 15%, 25% and 35%. In scenarios with midwifery staffing shortages above 15%, we modelled restricting community births in line with professional guidance on COVID-19 service reconfiguration. For shortages of 15%, we modelled expanding community births per the target of the Maternity Transformation programme. Results Expanding community births with 15% shortages required 0.0 and 0.1 whole-time equivalent more midwives in our respective trusts compared with baseline, representing 0% and 0.1% of overall staffing requirements net of shortages. Restricting home births with 25% shortages reduced midwifery staffing need by 0.1 midwives (–0.1% of staffing) and 0.3 midwives (–0.3%). Suspending community births with 35% shortages meant changes of –0.3 midwives (–0.3%) and –0.5 midwives (–0.5%) in the two trusts. Sensitivity analysis showed that our results were robust even under extreme assumptions. Conclusion Our model found that reconfiguring maternity services in response to shortages has a negligible effect on intrapartum and postnatal midwifery staffing needs. Given this, with lower degrees of shortage, managers can consider increasing community birth options where there is demand. In situations of severe shortage, reconfiguration cannot recoup the shortage and managers must decide how to modify service arrangements

The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein

In mammalian cells, MCTs (monocarboxylate transporters) require association with an ancillary protein to enable plasma membrane expression of the active transporter. Basigin is the preferred binding partner for MCT1, MCT3 and MCT4, and embigin for MCT2. In rat and rabbit erythrocytes, MCT1 is associated with embigin and basigin respectively, but its sensitivity to inhibition by AR-C155858 was found to be identical. Using RT (reverse transcription)–PCR, we have shown that Xenopus laevis oocytes contain endogenous basigin, but not embigin. Co-expression of exogenous embigin was without effect on either the expression of MCT1 or its inhibition by AR-C155858. In contrast, expression of active MCT2 at the plasma membrane of oocytes was significantly enhanced by co-expression of exogenous embigin. This additional transport activity was insensitive to inhibition by AR-C155858 unlike that by MCT2 expressed with endogenous basigin that was potently inhibited by AR-C155858. Chimaeras and C-terminal truncations of MCT1 and MCT2 were also expressed in oocytes in the presence and absence of exogenous embigin. L-Lactate Km values for these constructs were determined and revealed that the TM (transmembrane) domains of an MCT, most probably TM7–TM12, but not the C-terminus, are the major determinants of L-lactate affinity, whereas the associated ancillary protein has little or no effect. Inhibitor titrations of lactate transport by these constructs indicated that embigin modulates MCT2 sensitivity to AR-C155858 through interactions with both the intracellular C-terminus and TMs 3 and 6 of MCT2. The C-terminus of MCT2 was found to be essential for its expression with endogenous basigin

AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7–10

In the present study we characterize the properties of the potent MCT1 (monocarboxylate transporter 1) inhibitor AR-C155858. Inhibitor titrations of L-lactate transport by MCT1 in rat erythrocytes were used to determine the Ki value and number of AR-C155858-binding sites (Et) on MCT1 and the turnover number of the transporter (kcat). Derived values were 2.3±1.4 nM, 1.29±0.09 nmol per ml of packed cells and 12.2±1.1 s−1 respectively. When expressed in Xenopus laevis oocytes, MCT1 and MCT2 were potently inhibited by AR-C155858, whereas MCT4 was not. Inhibition of MCT1 was shown to be time-dependent, and the compound was also active when microinjected, suggesting that AR-C155858 probably enters the cell before binding to an intracellular site on MCT1. Measurement of the inhibitor sensitivity of several chimaeric transporters combining different domains of MCT1 and MCT4 revealed that the binding site for AR-C155858 is contained within the C-terminal half of MCT1, and involves TM (transmembrane) domains 7–10. This is consistent with previous data identifying Phe360 (in TM10) and Asp302 plus Arg306 (TM8) as key residues in substrate binding and translocation by MCT1. Measurement of the Km values of the chimaeras for L-lactate and pyruvate demonstrate that both the C- and N-terminal halves of the molecule influence transport kinetics consistent with our proposed molecular model of MCT1 and its translocation mechanism that requires Lys38 in TM1 in addition to Asp302 and Arg306 in TM8 [Wilson, Meredith, Bunnun, Sessions and Halestrap (2009) J. Biol. Chem. 284, 20011–20021]

Cardiovascular actions of the hypotensive agent, N, N-diallylmelamine (U-7720)

Diallylmelamine is an effective hypotensive agent in hypertensive dogs and rats, having a duration of action exceeding twenty-four hours from a single oral dose. It has limited efficacy in normotensive rats. Hypotensive activity of gradual onset is preceded by a latent period of up to two hours and becomes maximal six hours or more after dosing. This agent does not depress cardiac output or sympathetic vasoconstrictor activity. It is suggested that its hypotensive activity results from a direct effect upon vascular smooth muscle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46303/1/210_2004_Article_BF00245728.pd

Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations

The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we have previously employed drug-repositioning to identify the anti-amoebic drug, emetine dihydrochloride hydrate, as a potential candidate for repositioned use against malaria. Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with its anti-amoebic potency (ED50 26±32 uM), practical use of the compound has been limited by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner drug would present an opportunity for dose-reduction, thus increasing the therapeutic window. The lack of reliable and standardised methodology to enable the in vitro definition of synergistic potential for antimalarials is a major drawback. Here we use isobologram and combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define drug interactivity in an objective, automated manner. The method, based on the median effect principle proposed by Chou and Talalay, was initially validated for antimalarial application using the known synergistic combination (atovaquone-proguanil). The combination was used to further understand the relationship between SYBR Green viability and cytocidal versus cytostatic effects of drugs at higher levels of inhibition. We report here the use of the optimised Chou Talalay method to define synergistic antimalarial drug interactivity between emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential route to harness the nanomolar antimalarial efficacy of this affordable natural product

Low doses of caffeine reduce heart rate during submaximal cycle ergometry

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to examine the cardiovascular effects of two low-levels of caffeine ingestion in non habitual caffeine users at various submaximal and maximal exercise intensities.</p> <p>Methods</p> <p>Nine male subjects (19–25 yr; 83.3 ± 3.1 kg; 184 ± 2 cm), underwent three testing sessions administered in a randomized and double-blind fashion. During each session, subjects were provided 4 oz of water and a gelatin capsule containing a placebo, 1.5 mg/kg caffeine, or 3.0 mg/kg caffeine. After thirty minutes of rest, a warm-up (30 Watts for 2 min) the pedal rate of 60 rpm was maintained at a steady-state output of 60 watts for five minutes; increased to 120 watts for five minutes and to 180 watts for five minutes. After a 2 min rest the workload was 180 watts for one minute and increased by 30 watts every minute until exhaustion. Heart rate (HR) was measured during the last 15-seconds of each minute of submaximal exercise. Systolic blood pressure (BP) was measured at rest and during each of the three sub-maximal steady state power outputs. Minute ventilation (V_E), Tidal volume (V_T), Breathing frequency (Bf), Rating of perceived exertion (RPE), Respiratory exchange ratio (RER), and Oxygen consumption (VO₂) were measured at rest and during each minute of exercise.</p> <p>Results</p> <p>Caffeine at 1.5 and 3.0 mg/kg body weight significantly lowered (p < 0.05) HR during all three submaximal exercise intensities compared to placebo (range – 4 to 7 bpm lower) but not at rest or maximal exercise. BP was significantly higher (p < 0.05) at rest and after the 3 mg/kg caffeine vs placebo (116 ± 13 vs 123 ± 10 mm Hg). Neither dose of caffeine had any effect on BP during submaximal exercise. Caffeine had no effect on V_E, V_T, VO₂, RPE, maximal power output or time to exhaustion.</p> <p>Conclusion</p> <p>In non habitual caffeine users it appears that consuming a caffeine pill (1.5 & 3.0 mg/kg) at a dose comparable to 1–3 cups of coffee lowers heart rate during submaximal exercise but not at near maximal and maximal exercise. In addition, this caffeine dose also only appears to affect systolic blood pressure at rest but not during cycling exercise.</p