Delivering a “Dose of Hope”: A Faith-Based Program to Increase Older African Americans’ Participation in Clinical Trials

Background: Underrepresentation of older-age racial and ethnic minorities in clinical research is a significant barrier to health in the United States, as it impedes medical research advancement of effective preventive and therapeutic strategies. Objective: The objective of the study was to develop and test the feasibility of a community-developed faith-based intervention and evaluate its potential to increase the number of older African Americans in clinical research. Methods: Using a cluster-randomized design, we worked with six matched churches to enroll at least 210 persons. We provided those in the intervention group churches with three educational sessions on the role of clinical trials in addressing health disparity topics, and those in the comparison group completed surveys at the same timepoints. All persons enrolled in the study received ongoing information via newsletters and direct outreach on an array of clinical studies seeking participants. We evaluated the short-, mid-, and longer-term effects of the interventional program on clinical trial-related outcomes (ie, screening and enrollment)

Plio-Pleistocene productivity reconstructions in the Indian Monsoon region

The Indian Summer Monsoon (ISM) brings seasonal winds and rains to the Indian subcontinent. The winds cause surface ocean mixing in the southern Bay of Bengal (BoB), bringing nutrients to the surface that fuel ocean productivity and export of carbon to the sea floor. To improve the understanding of the role of monsoon winds in low-latitude surface ocean productivity and carbon export, the Plio-Pleistocene interval is ideal because boundary conditions were evolving. We aim to reconstruct variability in surface ocean and export productivity across the late-Pliocene and early-Pleistocene in response to ISM wind-driven mixing in the southern BoB. Here we analyse sediments from IODP Site U1443 (Exp. 353) from ~1.9-2.8 million years ago. A new benthic oxygen isotope (δ18O) stratigraphy (at ~3-thousand-year resolution) and age model tied to the global benthic δ18O stack are presented. We utilise these sediments to obtain bulk sediment X-ray fluorescence (XRF) core scanning elemental data and coccolithophore assemblages to infer changes in summer monsoon runoff and surface ocean productivity influenced by monsoon wind strength. We use % Florisphaera profunda (coccolithophore assemblage) along with bulk sediment XRF Br as productivity indicators and a “terrigenous” bulk sediment XRF elemental composition stack as a wind strength and runoff indicator. We observe increased productivity during glacials (MIS 96, 98, 100), coinciding with increased terrigenous input. This observation is coherent with previous low-latitude productivity records from the equatorial Pacific. However, in contrast to equatorial Pacific productivity records, influenced by obliquity, our southern BoB records show robust surface productivity (% F. profunda) and summer monsoon runoff (terrigenous stack) peaks in both the obliquity and precession bands. We will discuss linkages between monsoon wind and runoff across the Plio-Pleistocene in context with other monsoon records

Tied to the worldly work of writing: parent as ethnographer

Parent narratives have contributed to ethnographic accounts of the lives of autistic children (Kelly, 2005) but there are fewer examples of parents producing their own autoethnographies. This paper explores the affordances of an online blog for enabling a parent of an autistic child to produce a written record of practice which may be considered 'autoethnographic'. Richardson’s (2005) framework for ethnography as Creative Analytic Process is applied to extracts from a blog post in order to consider its contribution; reflexivity; aesthetic merit; and impact. The paper addresses the methodological and ethical implications of reconceptualising parents as researchers and the potential contribution of new writing platforms to the development of auto/ethnography. Key words: Autism, Auto/ethnography, Blog, Disability, Mothe

IGG3 Subclass Antibodies Recognize Antigenically Drifted Influenza Viruses and SARS-CoV-2 Variants Through Efficient Bivalent Binding

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 and BA.1 strains of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality but also for binding and neutralization of antigenically drifted viruses

Major contribution of the type II beta carbonic anhydrase CanB (Cj0237) to the capnophilic growth phenotype of Campylobacter jejuni

Campylobacter jejuni, the leading cause of human bacterial gastroenteritis, requires low environmental oxygen and high carbon dioxide for optimum growth, but the molecular basis for the carbon dioxide requirement is unclear. One factor may be inefficient conversion of gaseous CO2 to bicarbonate, the required substrate of various carboxylases. Two putative carbonic anhydrases (CAs) are encoded in the genome of C. jejuni strain NCTC 11168 (Cj0229 and Cj0237). Here, we show that the deletion of the cj0237 (canB) gene alone prevents growth in complex media at low (1% v/v) CO2 and significantly reduces the growth rate at high (5% v/v) CO2. In minimal media incubated under high CO2, the canB mutant grew on L-aspartate but not on the key C3 compounds L-serine, pyruvate and L-lactate, showing that CanB is crucial in bicarbonate provision for pyruvate carboxylase-mediated oxaloacetate synthesis. Nevertheless, purified CanB (a dimeric, anion and acetazolamide sensitive, zinc-containing type II beta-class enzyme) hydrates CO2 actively only above pH 8 and with a high Km (∼34 mM). At typical cytoplasmic pH values and low CO2, these kinetic properties might limit intracellular bicarbonate availability. Taken together, our data suggest CanB is a major contributor to the capnophilic growth phenotype of C. jejuni

The London exercise and pregnant smokers (LEAP) trial: A randomised controlled trial of physical activity for smoking cessation in pregnancy with an economic evaluation

Background: Smoking during pregnancy is the main preventable cause of poor birth outcomes. Improved methods are needed to help women to stop smoking during pregnancy. Pregnancy provides a compelling rationale for physical activity (PA) interventions as cessation medication is contraindicated or ineffective, and an effective PA intervention could be highly cost-effective.  Objective: To examine the effectiveness and cost-effectiveness of a PA intervention plus standard behavioural support for smoking cessation relative to behavioural support alone for achieving smoking cessation at the end of pregnancy.  Design: Multicentre, two-group, pragmatic randomised controlled trial and economic evaluation with follow-up at the end of pregnancy and 6 months postnatally. Randomisation was tratified by centre and a computer-generated sequence was used to allocate participants using a 1: 1 ratio. Setting: 13 hospitals offering antenatal care in the UK.  Participants: Women between 10 and 24 weeks’ gestation smoking five or more cigarettes a day before pregnancy and one or more during pregnancy.  Interventions: Participants were randomised to behavioural support for smoking cessation (control) or behavioural support plus a PA intervention consisting of supervised treadmill exercise plus PA consultations. Neither participants nor researchers were blinded to treatment allocation.  Main outcome measures: The primary outcome was self-reported, continuous smoking abstinence between a quit date and end of pregnancy, validated by expired carbon monoxide and/or salivary cotinine. Secondary outcomes were maternal weight, depression, birth outcomes, withdrawal symptoms and urges to smoke. The economic evaluation investigated the costs of the PA intervention compared with the control intervention.  Results: In total, 789 women were randomised (n = 394 PA, n = 395 control). Four were excluded post randomisation (two had been enrolled twice in sequential pregnancies and two were ineligible and randomised erroneously). The intention-to-treat analysis comprised 785 participants (n = 392 PA, n = 393 control). There was no significant difference in the rate of abstinence at the end of pregnancy between the PA group (7.7%) and the control group (6.4%) [odds ratio for PA group abstinence 1.21, 95% confidence interval (CI) 0.70 to 2.10]. For the PA group compared with the control group, there was a 33% (95% CI 14% to 56%), 28% (95% CI 7% to 52%) and 36% (95% CI 12% to 65%) significantly greater increase in self-reported minutes of moderate- and vigorous-intensity PA from baseline to 1 week, 4 weeks and 6 weeks respectively. Accelerometer data showed that there was no significant difference in PA levels between the groups. There were no significant differences between the groups for change in maternal weight, depression, withdrawal symptoms or urges to smoke. Adverse events and birth outcomes were similar between the groups except for there being significantly more caesarean births in the control group than in the PA group (28.7% vs. 21.3%; p < 0.023). The PA intervention was less costly than the control intervention by £35 per participant. This was mainly attributable to increased health-care usage in the control group. However, there was considerable statistical uncertainty around this estimate.  Conclusions: During pregnancy, offering an intervention combining supervised exercise and PA counselling does not add to the effectiveness of behavioural support for smoking cessation. Only 10% of participants had PA levels accessed by accelerometer and it is, therefore, unclear whether or not the lack of an effect on the primary outcome is the result of insufficient increases in PA. Research is needed to identify the smoking populations most suitable for PA interventions and methods for increasing PA adherence.  Trial registration: Current Controlled Trials ISRCTN48600346

The Role of the st313-td Gene in Virulence of Salmonella Typhimurium ST313

Multidrug-resistant Salmonella enterica serovar Typhimurium ST313 has emerged in sub-Saharan Africa causing severe infections in humans. Therefore, it has been speculated that this specific sequence type, ST313, carries factors associated with increased pathogenicity. We assessed the role in virulence of a gene with a yet unknown function, st313-td, detected in ST313 through comparative genomics. Additionally, the structure of the genomic island ST313-GI, harbouring the gene was determined. The gene st313-td was cloned into wild type S. Typhimurium 4/74 (4/74-C) as well as knocked out in S. Typhimurium ST313 02-03/002 (Δst313-td) followed by complementation (02-03/002-C). Δst313-td was less virulent in mice following i.p. challenge than the wild type and this phenotype could be partly complemented in trans, indicating that st313-td plays a role during systemic infection. The gene st313-td was shown not to affect invasion of cultured epithelial cells, while the absence of the gene significantly affects uptake and intracellular survival within macrophages. The gene st313-td was proven to be strongly associated to invasiveness, harboured by 92.5% of S. Typhimurium blood isolates (n = 82) and 100% of S. Dublin strains (n = 50) analysed. On the contrary, S. Typhimurium isolates of animal and food origin (n = 82) did not carry st313-td. Six human, non-blood isolates of S. Typhimurium from Belarus, China and Nepal harboured the gene and belonged to sequence types ST398 and ST19. Our data showed a global presence of the st313-td gene and in other sequence types than ST313. The gene st313-td was shown to be expressed during logarithmic phase of growth in 14 selected Salmonella strains carrying the gene. This study reveals that st313-td plays a role in S. Typhimurium ST313 pathogenesis and adds another chapter to understanding of the virulence of S. Typhimurium and in particular of the emerging sequence type ST313