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Background Healthcare professionals (HCPs) can play an important role in encouraging patients and their caregivers to be vaccinated. The objective of this qualitative study was to investigate HCPs’ perspectives on challenges in vaccine communication and unmet training needs in this domain. Methods Semi-structured interviews were conducted with 41 HCPs (mainly nurses and physicians) with vaccination roles (23 in England; 18 in France), gathering information on: (1) HCPs’ approach to vaccine conversations with patients; (2) Challenges of communicating about vaccines; (3) Vaccine-related training and learning resources available to HCPs, and; (4) HCPs’ training needs around vaccine communication. Results HCPs described a range of communication experiences that indicated insufficient time, information, and skills to confidently navigate difficult conversations with vaccine-hesitant patients. Communication skills were especially important to avoid conflict that could potentially damage the patient-provider relationship. Some HCPs interviewed had received communication training, but for most, this training was not specific to vaccination. Although general communication skills were transferable to vaccine conversations, most HCPs welcomed specific training and informational resources to support countering patients’ misconceptions or misinformation about vaccines. Conclusions HCPs would benefit from training tailored to address vaccine communication with patients, and this should be part of a systemic approach that also provides time and space to have effective vaccine conversations.

Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV-1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release.

Intracellular protein trafficking through secretory and endocytic pathways depends on the function of adaptor proteins that bind motifs on cargo proteins. The adaptor proteins then recruit coat proteins such as clathrin, enabling the formation of a transport vesicle. While studying the role of the clathrin adaptor proteins, AP-1, AP-2 and AP-3 in viral protein trafficking, we discovered that AP-1 and AP-3 potentially have a role in successful transfection of mammalian cells with DNA-liposome complexes (lipoplexes). We showed that AP-1, -2 and -3 are not required for lipoplexes to enter cells, but that lipoplexes and/or released DNA are unable to reach the nucleus in the absence of AP-1 or AP-3, leading to minimal exogenous gene expression. In contrast, gene expression from liposome-delivered mRNA, which does not require nuclear entry, was not impaired by the absence of AP-1 or AP-3. Despite the use of lipoplexes to mediate gene delivery being so widely used in cell biology and, more recently, gene therapy, the mechanism by which lipoplexes or DNA reach the nucleus is poorly characterised. This work sheds light on the components involved in this process, and demonstrates a novel role for AP-1 and AP-3 in trafficking lipoplexes.

Vaccinations for seasonal influenza and pertussis have been recommended for pregnant women in England since 2010 and 2012, respectively. Uptake rates are suboptimal with large regional variations. To improve uptake, from 2016 onwards maternity trusts were commissioned to offer pertussis (and other) vaccinations in addition to these being available in primary care. Since 2021, Covid-19 vaccination has also been recommended for pregnant women. Overall maternal vaccination rates are routinely available, but not the relative provision by maternity trusts. We aimed to describe the national picture of maternity trust provision of maternal vaccinations, including how the maternity trust vaccination programme has progressed. Cross-sectional survey plus comparisons with 2017–18 figures for maternity trust provision of pertussis vaccination, and with UKHSA data for total pertussis vaccination. Twelve NHS commissioners participated (from 13/06/22 to 31/03/23) providing data for 120 (of a total 124) maternity trusts across England. All 120 (100%) trusts were commissioned to deliver influenza, and 107 (89%) to deliver pertussis vaccinations, though not all actually administered the vaccines; 29% offered Covid-19 vaccinations. For 2021–22 we found a mean of 25% (range 0–81.3%) women were vaccinated for pertussis (a large increase compared with previous estimates for 2017–18); and 11% (range 0–74.2%) for influenza, via their maternity trust. Commissioners reported a negative impact of the pandemic on routine vaccination provision. There was indication of efficiency by vaccinating women attending for other appointments. There are diverse mechanisms for reporting pertussis and influenza vaccinations administered at maternity trusts back to primary care, which may be inefficient for maternity staff workload and accuracy of data transfer (especially for pertussis). A high proportion of maternity trusts provide both pertussis and influenza vaccinations, despite a negative impact of the pandemic. Reasons for large between-trust variation in vaccination rates should be explored to improve uptake and equity.

AimTo investigate primary care clinicians’ views of a prototype locally relevant, real-time viral surveillance system to assist diagnostic decision-making and antibiotic prescribing for paediatric respiratory tract infections (RTI). Clinicians’ perspectives on the content, anticipated use and impact were explored to inform intervention development.BackgroundChildren with RTIs are overprescribed antibiotics. Pressures on primary care and diagnostic uncertainty can lead to decisional biases towards prescribing. We hypothesise that real-time paediatric RTI surveillance data could reduce diagnostic uncertainty and help reduce unnecessary antibiotic prescribing.MethodologySemistructured one-to-one interviews with 21 clinicians from a range of urban general practitioner surgeries explored the clinical context and views of the prototype system. Transcripts were analysed using thematic analysis.ResultsThough clinicians self-identified as rational (not over)prescribers, cognitive biases influenced antibiotic prescribing decisions. Clinicians sought to avoid ‘anticipated regret’ around not prescribing for a child who then deteriorated. Clinicians were not aware of formal infection surveillance information sources (tending to assume many viruses are around), perceiving the information as novel and potentially useful. Perceptions of surveillance information as presented included: not relevant to decision-making/management; useful to confirm decisions post hoc; and increasing risks of missing sick children. Clinicians expressed wariness of using population-level data to influence individual patient decision-making and expressed preference for threat (high-risk) information identified by surveillance, rather than reassuring information about viral RTIs.ConclusionsMore work is needed to develop a surveillance intervention if it is to beneficially influence decision-making and antibiotic prescribing in primary care. Key challenges for developing interventions are how to address cognitive biases and how to communicate reassuring information to risk-oriented clinicians.

The RNA binding protein Unr, which contains five cold shock domains, has several specific roles in post-transcriptional control of gene expression. It can act as an activator or inhibitor of translation initiation, promote mRNA turnover, or stabilise mRNA. Its role depends on the mRNA and other proteins to which it binds, which includes cytoplasmic poly(A) binding protein 1 (PABP1). Since PABP1 binds to all polyadenylated mRNAs, and is involved in translation initiation by interaction with eukaryotic translation initiation factor 4G (eIF4G), we investigated whether Unr has a general role in translational control. We found that Unr strongly stimulates translation in vitro , and mutation of cold shock domains 2 or 4 inhibited its translation activity. The ability of Unr and its mutants to stimulate translation correlated with its ability to bind RNA, and to interact with PABP1. We found that Unr stimulated the binding of PABP1 to mRNA, and that Unr was required for the stable interaction of PABP1 and eIF4G in cells. siRNA-mediated knockdown of Unr reduced the overall level of cellular translation in cells, as well as that of cap-dependent and IRES-dependent reporters. These data describe a novel role for Unr in regulating cellular gene expression.

A 2-year (2017 and 2018) field lysimeter study was carried out to examine the effect of titanium dioxide nanoparticles (TiO 2 NPs) in irrigation wastewater on soil characteristics and potato ( Solanum tuberosum L.) yield. Potatoes were planted in lysimeters (1.00 m × 0.45 m) in sandy soil and subjected to four treatments: freshwater (FW), wastewater (WW), freshwater + TiO 2 NPs (FW + NP) and wastewater + TiO 2 NPs (WW + NP), in triplicate. Potato tubers were harvested at maturity (120 days after planting). Both the TiO 2 NPs (with/without 1 mg L −1  TiO 2 NPs) and irrigation treatments (FW vs. WW) had a significant effect ( p ≤ 0.05) on chlorophyll content; however, they had little or no effect on soil physicochemical parameters (cation exchange capacity (CEC), pH and soil organic matter (SOM)), plant growth parameters (plant height, above-ground and root fresh weight) or yield (tuber weight, number of tubers and tuber grading). For both years, the total nitrogen content of the leaves increased consistently together with leaf chlorophyll content. Furthermore, tuber yield under FW, WW and WW + NP treatments were higher in the first year than in the second, likely due to higher growing season temperatures in the second year. This study furthers the knowledge on the impact of TiO 2 NPs on plant growth by showing that at 1 mg L −1 , irrigation water can increase greenness without inhibiting plant growth and yield. In addition, the potato plants, irrigated with water containing TiO 2 NPs, did not become infected with early and late blight diseases either year.

Background There is a need to reduce unnecessary general practitioner (GP) consultations and improve antibiotic stewardship in primary care. Respiratory tract infections (RTIs) in children are the most common reason for consulting and prescribing. Most RTI research is conducted at the point of consultation, leaving a knowledge gap regarding the population burden of RTIs. Methods Community-based, online prospective inception cohort study with nested qualitative study, to evaluate the feasibility and acceptability of collecting RTI symptom and microbiological data from children recruited prior to RTI onset. Results Parents of 10,310 children were invited. Three hundred thirty-one parents of 485 (4.7%) children responded and completed baseline data. Respondents were less socioeconomically deprived ( p  < 0.001) with younger (median ages 4 vs. 6 years, p  < 0.001) children than non-respondents. The same parents reported 346 RTI episodes in 259 children, and 305 RTIs (in 225 children) were retained to parent-reported symptom resolution. Restricting analyses to the first RTI episode per family (to account for clustering effects), parents fully completed symptom diaries for 180 (87%) of 192 first illness episodes. Research nurses conducted home visits for 199 RTI episodes, collecting complete (symptomatic) swab sets in 195 (98%). Parents collected 194 (98% of 199 possible) symptomatic (during the nurse visit) and 282 (92% of 305 possible) asymptomatic swab sets (on symptom resolution, no nurse present). Interviews with 30 mothers and 11 children indicated study acceptability. Conclusions Invitation response rates were in the expected range. The high retention and qualitative evidence suggest that community-based paediatric syndromic and microbiological surveillance research is feasible.

Wastewater can supplement freshwater in agriculture; however, it contains toxic heavy metals such as cadmium, chromium, and lead that are hazardous to humans and the environment. We investigated the effects of barley straw biochar, green and table waste compost, and their mix on heavy metal transport in soil and uptake by potatoes (Solanum tuberosum L.) irrigated with synthetic wastewater for two years. In both years, amending soil with compost significantly reduced (p ≤ 0.05) cadmium uptake in potato flesh, skin, roots, and stems; zinc uptake in potato skin and roots; and copper uptake in potato flesh due to increased soil cation-exchange capacity, dissolved organic carbon, and soil pH. Co-amending the soil with compost and 3% biochar significantly reduced (p ≤ 0.05) the bioavailability of cadmium, copper, and zinc in the contaminated soil. Relative to the non-amended soils, soil amendment with biochar, compost, and their mix affected neither the transport of chromium, iron, and lead in the soils nor their uptake by potatoes. It was concluded that amending soil with barley straw biochar and/or compost produced from city green table waste could be used to improve the safety of wastewater irrigated potatoes, depending on the biochar application rate and heavy metal type.

IntroductionPaediatric respiratory tract infections (RTIs) are common reasons for primary care consultations and antibiotic prescribing. Locally relevant syndromic and microbiological surveillance information has the potential to improve the care of children with RTIs by normalising illness (parents) and reducing uncertainty (clinicians). Currently, most RTI studies are conducted at the point of healthcare service consultation, leaving the community burden, microbiology, symptom duration and proportion consulting largely unknown. This study seeks to establish the feasibility of (mainly online) participant recruitment and retention, and the acceptability/comparability of parent versus nurse-collected microbiological sampling, to inform the design of a future surveillance intervention study. Evidence regarding consultation rates and symptom duration is also sought.Methods and analysisA community-based, feasibility prospective inception cohort study, recruiting children aged ≥3 months and <16 years and their parents via general practitioner surgery invitation letter, aiming to collect data on 300 incident RTIs by July 2016. Following informed consent, parents provide baseline (demographic) data online, and respond to weekly emails to confirm the absence/presence of new RTI symptoms. Once symptomatic, parents provide daily data online (RTI symptoms, school/day-care attendance, time off work, health service use, medication), and a research nurse visits to collect clinical examination data and microbiological (nasal and saliva) swabs. Parents are invited to provide symptomatic (at nurse visit, but without nurse assistance) and asymptomatic (alone) swabs on recovery. A review of primary care medical notes will gather medical history, health service utilisation, referral and antibiotic prescribing rates. Feasibility will be assessed using recruitment and retention rates, data completeness; and acceptability by quantitative survey and qualitative interviews. Symptomatic parent and nurse swab pairs will be compared for microbe isolation.