BACKGROUND: Exercise Referral Schemes (ERSs) have been implemented across Western nations to stimulate an increase in adult physical activity but evidence of their effectiveness and cost-effectiveness is equivocal. Poor ERS uptake and adherence can have a negative impact on effectiveness and cost-effectiveness and, if patterned by socio-demographic factors, can also introduce or widen health inequalities. Different modes of ERS delivery have the potential to reduce costs and enhance uptake and adherence. The primary aim of this study was to examine the effect of different programmes of ERS delivery on scheme uptake and adherence. Secondary aims were to examine the effect of socio-demographic factors on scheme uptake and adherence, and the impact of delivery mode on the expected resource and corresponding costs of delivering core parts of the programme.
METHODS: This was an observational cohort study with cost analysis. Routine monitoring data covering a three-year period (2019-2021) from one large UK ERS (number of patients = 28,917) were analysed. During this period three different programmes of delivery were operated in succession: standard (all sessions delivered face-to-face at a designated physical location), hybrid (sessions initially delivered face-to-face and then switched to remote delivery in response to the Covid-19 pandemic), and modified (sessions delivered face-to-face, remotely, or a combination of the two, as determined on a case-by-case basis according to Covid-19 risk and personal preferences). Multi-level binary logistic and linear regression were performed to examine the effect of programme of delivery and socio-demographic characteristics on uptake and adherence. Cost data were sourced from regional-level coordinators and through NERS audits supplied by national-level NERS managers and summarised using descriptive statistics.
RESULTS: There was no effect of programme of delivery on scheme uptake. In comparison to those on the standard programme (who attended a mean of 23.1 exercise sessions) those on the modified programme had higher adherence (mean attendance of 25.7 sessions) while those on the hybrid programme had lower adherence (mean attendance of 19.4 sessions). Being older, or coming from an area of lower deprivation, increased the likelihood of uptake and adherence. Being female increased the chance of uptake but was associated with lower adherence. Patients referred to the programme from secondary care were more likely to take up the programme than those referred from primary care for prevention purposes, however their attendance at exercise sessions was lower. The estimated cost per person for face-to-face delivery of a typical 16-week cycle of the scheme was £65.42. The same cycle of the scheme delivered virtually (outside of a pandemic context) was estimated to cost £201.71 per person.
CONCLUSIONS: This study contributes new evidence concerning the effect of programme of delivery on ERS uptake and adherence and strengthens existing evidence concerning the effect of socio-economic factors. The findings direct the attention of ERS providers towards specific patient sub-groups who, if inequalities are to be addressed, require additional intervention to support uptake and adherence. At a time when providers may be considering alternative programmes of delivery, these findings challenge expectations that implementing virtual delivery will necessarily lead to cost savings.

BACKGROUND: Bowel cancer screening using faecal immunochemical testing is provided in the United Kingdom with the aim of reducing mortality from colorectal cancer. However, there are low participant rates among ethnic minorities across the United Kingdom. Faith-placed interventions have the potential to improve screening rates among such populations, but studies examining their effectiveness are scarce.
METHODS: We delivered a presentation on bowel cancer screening to 204 Muslims in seven mosques in East London (intervention group). All participants completed a questionnaire regarding attitudes, perceptions and knowledge of bowel cancer screening before and after the presentation. Concurrently, we administered the questionnaire to 72 subjects attending a mosque that did not receive the presentation (comparison group).
RESULTS: The intervention group showed a greater willingness to do the test (90% vs. 67%, p < 0.001) and to recommend it to others (96% vs. 74%, p < 0.001), ability to complete the test by themselves (94% vs. 56%, p < 0.001) and confidence in noticing symptoms (78% vs. 32%, p < 0.001) after the presentation compared to before. There was a significant difference between the intervention group post-presentation and the comparison group on intention to do the test (90% vs. 79%, p = 0.02), recommending it to others (96% vs. 83%, p < 0.001), and confidence in their ability to complete the test by themselves (94% vs. 63%, p < 0.001).
CONCLUSIONS: A culture-sensitive, faith-placed health education intervention delivered in mosques can substantially improve knowledge of bowel cancer screening and increase the intention to participate in the screening programme.
UNASSIGNED: The intervention presentation was developed using insights from four public involvement sessions with four to six members representative of the East London Muslim community. The sessions sought attendees\' thoughts on appropriate ways to approach the intervention design for their community and asked for their views on the acceptability, appropriateness of messaging, format/design and likely impact of the presentation. Their views were then utilised to improve the presentation.

UNASSIGNED: Achieving the 95-95-95 targets require an efficient and innovative person-centered approach, specifically community-based differentiated service delivery (DSD), to improve access to human immunodeficiency virus (HIV) services and reduce burdens on the health system. Therefore, this study aimed to assess the uptake of community-based DSD models and associated factors among people living with HIV (PLHIV).
UNASSIGNED: A multicenter cross-sectional study was conducted among PLHIV in public health facilities in South Ethiopia. Data were collected and entered into EpiData version 3.1 before being exported to Stata version 14 for further analysis. In the bivariable logistic regression analysis, variables with a p-value of ≤0.25 were included in the multivariable logistic regression analysis. A p-value of <0.05 was used to identify statistically significant factors.
UNASSIGNED: Among 381 stable PLHIV, 55.91% were women. The median age (interquartile range) was 40 years (27-53). The uptake of community-based DSD models was 19.16%. Residence and disclosure were the two independent factors significantly associated with the uptake of community-based DSD models.
UNASSIGNED: One out of five stable PLHIV on antiretroviral therapy uptake the community-based DSD models. Improvement in uptake is needed in Ethiopia\'s resource-limited healthcare system to better achieve the 95-95-95 targets.

Aconitate decarboxylase-1 (ACOD1) is expressed by activated macrophages and generates itaconate that exerts anti-microbial and immunoregulatory effects. ACOD1-itaconate is essential for macrophage-mediated control of the intracellular pathogen Coxiella (C.) burnetii, which causes Q fever. Two isomers of itaconate, mesaconate and citraconate, have overlapping yet distinct activity on macrophage metabolism and inflammatory gene expression. Here, we found that all three isomers inhibited the growth of C. burnetii in axenic culture in ACCM-2 medium. However, only itaconate reduced C. burnetii replication efficiently in Acod1-/- macrophages. In contrast, addition of citraconate strongly increased C. burnetii replication in Acod1+/- macrophages, whereas mesaconate weakly enhanced bacterial burden in Acod1-/- macrophages. Analysis of intracellular isomers showed that exogenous citraconate and mesaconate inhibited the generation of itaconate by infected Acod1+/- macrophages. Uptake of added isomers into Acod1-/- macrophages was increased after infection for itaconate and mesaconate, but not for citraconate. Mesaconate, but not citraconate, competed with itaconate for uptake into macrophages. Taken together, inhibition of itaconate generation by macrophages and interference with the uptake of extracellular itaconate could be identified as potential mechanisms behind the divergent effects of citraconate and mesaconate on C. burnetii replication in macrophages or in axenic culture.

Extracellular vesicles (EVs) are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type. A variety of biomolecules, including proteins, lipids, coding and non-coding RNAs, and mitochondrial DNA, can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells, leading to alterations in the recipient cells, suggesting that EVs play an important role in intercellular communication. EVs play effective roles in physiology and pathology and could be used as diagnostic and therapeutic tools. At present, although the mechanisms of exosome biogenesis and secretion in donor cells are well understood, the molecular mechanism of EV recognition and uptake by recipient cells is still unclear. This review summarizes the current understanding of the molecular mechanisms of EVs\' biological journey in recipient cells, from recognition to uptake and cargo release. Furthermore, we highlight how EVs escape endolysosomal degradation after uptake and thus release cargo, which is crucial for studies applying EVs as drug-targeted delivery vehicles. Knowledge of the cellular processes that govern EV uptake is important to shed light on the functions of EVs as well as on related clinical applications.
胞外囊泡（EVs）是几乎所有细胞均能分泌的纳米级脂质双层囊泡，可通过将其内含的多种包括蛋白质、脂质、编码和非编码RNA、线粒体DNA等在内的生物活性分子递送到邻近和远处的受体细胞中，以改变受体细胞功能，从而实现细胞间的信息交流。EVs在生理和病理过程中均发挥着重要作用，可用于疾病诊疗。尽管EVs在供体细胞中的生物发生和分泌机制已基本清晰，但受体细胞对EVs的识别和摄取的分子机制尚不清楚。本文对EVs进入受体细胞的生物过程包括受体细胞对EVs的识别、摄取以及EVs的货物释放进行综述，并重点关注了EVs在摄取后如何通过“溶酶体逃逸”，从而释放货物，将有助于推进EVs作为药物递送载体的研究。此外，了解和控制EVs在受体细胞中的有效摄取，对阐明EVs的功能及其临床应用同样至关重要。.

Systemic plant protection products, such as neonicotinoids (NIs), are capable of being translocated throughout a plant. Although NIs are less toxic to mammals, fish, and birds, their impact on microbial and non-target insects is of concern. This study investigates the uptake, translocation, and accumulation of the NI, imidacloprid (IMI), in romaine lettuce (Lactuca sativa L. var. longipolia). Exposing 15-day-old seedlings to \"10 mg/L\" of IMI, the effects on microbial communities in both cultivated (CS) and non-cultivated soil (NCS) were studied along with IMI translocation within plant tissues. The concentrations of IMI in soil varied temporally and between soil types after initial application, with a decrease from 2.0 and 7.7 mg/kg on the first day of sampling to 0.5 and 2.6 mg/kg on the final sampling day (day 35) for CS and NCS, respectively. The half-life of IMI soil was 10.7 and 72.5 days in CS and NCS, respectively, indicating that IMI degraded more quickly in CS, possibly due to smaller grain size, aeration, microbial degradation, and water flow. The accumulated concentrations of IMI in lettuce tissues ranged from 12.4 ± 0.2 and 18.7± 0.9 mg/kg in CS and NCS, respectively. The highest concentration of IMI was found in the shoots, followed by the roots, whereas the soil showed the lowest IMI residuals at the end of the trial. Soil bacteria and fungi were altered by the application of IMI, with a lower abundance index within the bacterial community, indicating a negative impact on the distribution of bacteria in the soil.

Human Papillomavirus (HPV) vaccine coverage was <50% in France in 2022 and even lower among socially disadvantaged populations. We aimed to evaluate socio-demographic determinants of HPV vaccine awareness, uptake, and intention among parents of adolescents, and related attitudes and knowledge items. Parents of adolescents attending middle schools across France, who participated in a randomized trial responded to an anonymous baseline survey, conducted between November 2021 and February 2022. We used logistic regression models adjusting for a child\'s age and sex to explore sociodemographic determinants (including at-home multilingualism, occupational categories, local deprivation index and urbanity) of HPV vaccine awareness, uptake, and intention. Among the 1889 participants from 61 schools, parents working as factory workers/farmers had significantly lower odds of vaccine awareness compared to executives/professionals, both if they reported (OR = 0.07; 0.03-0.15) or not (OR = 0.20; 0.11-0.36) speaking also another language than French at home. Parents in lower occupational categories with multilingual families were less likely to have the intention to vaccinate their child (OR = 0.19; 0.07-0.56). Recent physician visit or vaccine offer was strong positive determinants of awareness, uptake and intention. A substantial gradient across occupational categories was observed for attitudes and knowledge around HPV vaccine usefulness, safety, and accessibility. This study confirms the disparities on HPV vaccine uptake in France and provides insight into mechanisms of social disparities in HPV vaccine awareness, access and intention.

UNASSIGNED: Sexual and reproductive healthcare is essential for all individuals, including LGBTQ+ individuals. However, lesbians and bisexual women often lack tailored services, leading to underutilization. This study aimed to assess the availability and uptake of sexual and reproductive health services for lesbian and bisexual Bulawayo women.
UNASSIGNED: A cross-sectional study surveyed 67 lesbian and bisexual women recruited through the Voice of the Voiceless Organization. The participants completed a structured questionnaire on available services, factors influencing their uptake, and access challenges. Cross-tabulation was used to examine the associations between variables. Data were analyzed using Microsoft Excel and STATA Version 15 S.E.
UNASSIGNED: Most respondents were bisexual women aged 35 years. Cross-tabulations revealed significant associations between delayed or avoided services and the absence of specific services for lesbians and bisexual women as well as the presence of gender identity nondiscrimination policies.
UNASSIGNED: Sexual and reproductive health programs play a vital role in meeting lesbian and bisexual women\'s needs. Improving service uptake requires strengthening the linkages between clinics and sexual health education programs, providing lesbian and bisexual women-friendly clinical services, and ensuring access to comprehensive information.

Existing models for estimating pesticide bioconcentration in earthworms exhibit limited applicability across different chemicals, soils and species which restricts their potential as an alternative, intermediate tier for risk assessment. We used experimental data from uptake and elimination studies using three earthworm species (Lumbricus terrestris, Aporrectodea caliginosa, Eisenia fetida), five pesticides (log Kow 1.69-6.63) and five soils (organic matter content = 0.972-39.9 wt %) to produce a first-order kinetic accumulation model. Model applicability was evaluated against a data set of 402 internal earthworm concentrations reported from the literature including chemical and soil properties outside the data range used to produce the model. Our models accurately predict body load using either porewater or bulk soil concentrations, with at least 93.5 and 84.3% of body load predictions within a factor of 10 and 5 of corresponding observed values, respectively. This suggests that there is no need to distinguish between porewater and soil exposure routes or to consider different uptake and elimination pathways when predicting earthworm bioconcentration. Our new model not only outperformed existing models in characterizing earthworm exposure to pesticides in soil, but it could also be integrated with models that account for earthworm movement and fluctuating soil pesticide concentrations due to degradation and transport.

3D spheroids of primary human hepatocytes (3D PHH) retain a differentiated phenotype with largely conserved metabolic function and proteomic fingerprint over weeks in culture. As a result, 3D PHH are gaining importance as a model for mechanistic liver homeostasis studies and in vitro to in vivo extrapolation (IVIVE) in drug discovery. However, the kinetics and regulation of drug transporters have not yet been assessed in 3D PHH. Here, we used organic cation transporter 1 (OCT1/SLC22A1) as a model to study both transport kinetics and the long-term regulation of transporter activity via relevant signalling pathways. The kinetics of the OCT1 transporter was studied using the fluorescent model substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) and known OCT1 inhibitors in individual 3D PHH. For long-term studies, 3D PHH were treated with xenobiotics for seven days, after which protein expression and OCT1 function were assessed. Global proteomic analysis was used to track hepatic phenotypes as well as prototypical changes in other regulated proteins, such as P-glycoprotein and Cytochrome P450 3A4. ASP+ kinetics indicated a fully functional OCT1 transporter with a Km value of 14 ± 4.0µM as the mean from three donors. Co-incubation with known OCT1 inhibitors decreased the uptake of ASP+ in the 3D PHH spheroids by 35-52%. The long-term exposure studies showed that OCT1 is relatively stable upon activation of nuclear receptor signalling or exposure to compounds that could induce inflammation, steatosis or liver injury. Our results demonstrate that 3D PHH spheroids express physiologically relevant levels of fully active OCT1 and that its transporter kinetics can be accurately studied in the 3D PHH configuration. We also confirm that OCT1 remains stable and functional during the activation of key metabolic pathways that alter the expression and function of other drug transporters and drug-metabolizing enzymes. These results will expand the range of studies that can be performed using 3D PHH.