The PROMISES study: A mixed methods approach to explore the acceptability of salivary progesterone testing for preterm birth risk among pregnant women and trained frontline healthcare workers in rural India

Introduction India has an overall neonatal mortality rate of 28/1000 live births, with higher rates in rural India. Approximately 3.5 million pregnancies in India are affected by preterm birth (PTB) annually and contribute to approximately a quarter of PTBs globally. Embedded within the PROMISES study (which aims to validate a low-cost salivary progesterone test for early detection of PTB risk), we present a mixed methods explanatory sequential feasibility substudy of the salivary progesterone test. Methods A pretraining and post-training questionnaire to assess Accredited Social Health Activists (ASHAs) (n=201) knowledge and experience of PTB and salivary progesterone sampling was analysed using the McNemar test. Descriptive statistics for a cross-sectional survey of pregnant women (n=400) are presented in which the acceptability of this test for pregnant women is assessed. Structured interviews were undertaken with ASHAs (n=10) and pregnant women (n=9), and were analysed using thematic framework analysis to explore the barriers and facilitators influencing the use of this test in rural India. Results Before training, ASHAs' knowledge of PTB (including risk factors, causes, postnatal support and testing) was very limited. After the training programme, there was a significant improvement in the ASHAs' knowledge of PTB. All 400 women reported the salivary test was acceptable with the majority finding it easy but not quick or better than drawing blood. For the qualitative aspects of the study, analysis of interview data with ASHAs and women, our thematic framework comprised of three main areas: implementation of intervention; networks of influence and access to healthcare. Qualitative data were stratified and presented as barriers and facilitators. Conclusion This study suggests support for ongoing investigations validating PTB testing using salivary progesterone in rural settings

Effects of the fatty acid amide hydrolase inhibitor URB597 on coping behavior under challenging conditions in mice

RATIONALE: Recent evidence suggests that in addition to controlling emotional behavior in general, endocannabinoid signaling is engaged in shaping behavioral responses to challenges. This important function of endocannabinoids is still poorly understood. OBJECTIVES: Here we investigated the impact of blockade of fatty acid amide hydrolase (FAAH), the degrading enzyme of anandamide on behavioral responses induced by challenges of different intensity. METHODS: Mice treated with FAAH inhibitor URB597 were either manually restrained on their backs (back test) or received foot-shocks. RESULTS: The behavior of mice showed bimodal distribution in the back test: they either predominantly showed escape attempts or equally distributed time between passivity and escape. URB597 increased escapes in animals with low escape scores. No effects were noticed in mice showing high escape scores, which is likely due to a ceiling effect. We hypothesized that stronger stressors would wash out individual differences in coping; therefore, we exposed mice to foot-shocks that decreased locomotion and increased freezing in all mice. URB597 ameliorated both responses. The re-exposure of mice to the shock cage 14 days later without delivering shocks or treatment was followed by reduced and fragmented sleep as shown by electrophysiological recordings. Surprisingly, sleep was more disturbed after the reminder than after shocks in rats receiving vehicle before foot-shocks. These reminder-induced disturbances were abolished by URB597 administered before shocks. CONCLUSIONS: These findings suggest that FAAH blockade has an important role in the selection of behavioral responses under challenging conditions and-judging from its long-term effects-that it influences the cognitive appraisal of the challenge

Apoptosis-like cell death in Leishmania donovani treated with KalsomeTM10, a new liposomal amphotericin B

The present study aimed to elucidate the cell death mechanism in Leishmania donovani upon treatment with KalsomeTM10, a new liposomal amphotericin B. Methodology/Principal findings We studied morphological alterations in promastigotes through phase contrast and scanning electron microscopy. Phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential and disruption of mitochondrial integrity was determined by flow cytometry using annexinV-FITC, JC-1 and mitotraker, respectively. For analysing oxidative stress, generation of H2O2 (bioluminescence kit) and mitochondrial superoxide O2 − (mitosox) were measured. DNA fragmentation was evaluated using terminal deoxyribonucleotidyl transferase mediated dUTP nick-end labelling (TUNEL) and DNA laddering assay. We found that KalsomeTM10 is more effective then Ambisome against the promastigote as well as intracellular amastigote forms. The mechanistic study showed that KalsomeTM10 induced several morphological alterations in promastigotes typical of apoptosis. KalsomeTM10 treatment showed a dose- and time-dependent exposure of PS in promastigotes. Further,study on mitochondrial pathway revealed loss of mitochondrial membrane potential as well as disruption in mitochondrial integrity with depletion of intracellular pool of ATP. KalsomeTM10 treated promastigotes showed increased ROS production, diminished GSH levels and increased caspase-like activity. DNA fragmentation and cell cycle arrest was observed in KalsomeTM10 treated promastigotes. Apoptotic DNA fragmentation was also observed in KalsomeTM10 treated intracellular amastigotes. KalsomeTM10 induced generation of ROS and nitric oxide leads to the killing of the intracellular parasites. Moreover, endocytosis is indispensable for KalsomeTM10 mediated anti-leishmanial effect in host macrophag

Rapid Transient Production in Plants by Replicating and Non-Replicating Vectors Yields High Quality Functional Anti-HIV Antibody

Background: The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product. Methodology/Principal Findings: To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV) RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue) of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER). Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO) cell-produced 2G12. Conclusions: Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for biopharmaceutical development and production

Sharing vocabularies: towards horizontal alignment of values-driven business functions

This paper highlights the emergence of different ‘vocabularies’ that describe various values-driven business functions within large organisations and argues for improved horizontal alignment between them. We investigate two established functions that have long-standing organisational histories: Ethics and Compliance (E&C) and Corporate Social Responsibility (CSR). By drawing upon research on organisational alignment, we explain both the need for and the potential benefit of greater alignment between these values-driven functions. We then examine the structural and socio-cultural dimensions of organisational systems through which E&C and CSR horizontal alignment can be coordinated to improve synergies, address tensions, and generate insight to inform future research and practice in the field of Business and Society. The paper concludes with research questions that can inform future scholarly research and a practical model to guide organizations’ efforts towards inter-functional, horizontal alignment of values-driven organizational practice