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The interactions of fly ash aerosol with lung cells were tested in vitro via exposure at the air- liquid interface or via suspension in medium. The experimental set-up for aerosol generation, dilution and exposure of cells under conditions that do not affect the cell viability by the treatment procedure was shown to work in principle. First experiments showed only low effects concerning metabolic activity and release of pro-inflammatory mediators in NR8383 alveolar macrophages and BEAS-2B epithelial cells. Exposure to fly ash resuspended in culture medium neither reduced the viability nor induced the release of tumor necrosis factor a (TNFα), macrophage inflammatory protein-2 (MIP-2) and nitrite in NR8383 macrophages at the indicated concentrations. These conditions, however, enhanced the production of the lipopolysaccharide (LPS)-induced cytokines and inhibited the LPS-induced nitrite release considerably. BEAS-2B cells produced interleukin-6 (IL-6) and IL-8 after fly ash exposure, and this could be further amplified by TNFα. The results support the hypothesis that ambient particulate matter may contribute to the aggravation of lung diseases. [ABSTRACT FROM AUTHOR]

Introduction: men who have sex with men (MSM) are disproportionately affected by hepatitis B virus (HBV) and hepatitis C virus (HCV) worldwide. In Benin, there are no data on MSM. The purpose of this study was to estimate HBV and HCV prevalence and HBV-associated factors in MSM who were HIV negative., Methods: we conducted an analytical cross-sectional study. A two-degree random sampling was used to recruit 204 MSM. An immunochromatographic rapid test and enzyme immunoassays were used to detect HBV and HCV antigens/antibodies. Log-binomial regression was used to identify factors associated with HBV., Results: HbsAg positivity, history of hepatitis B infection and hepatitis C prevalences were 37.7%, 8.8 %, and 0.9 %, respectively. HBsAg positivity and history of hepatitis B were more prevalent in MSM aged ≥30 years compared to younger subjects: 16.7% versus 6.4% (p<0.0001) and 66.7% versus 28.8% (p<0.0001), respectively. Sexual intercourse under the effect of drug or alcohol and living in couple were also associated with HBV., Conclusion: the prevalence of hepatitis C was low, but hepatitis B was common, especially among older MSM. Screening and vaccination against hepatitis B should be strengthened in this population., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Luc Béhanzin et al.)

Objectives: This study aims to assess the prevalence and factors associated with anal high-risk human papilloma virus (HR-HPV)., Design: A cross-sectional study conducted from 24 August 2020 to 24 November 2020., Setting: Primary care, Cotonou, Benin., Participants: 204 HIV-negative men who have sex with men initiating oral pre-exposure prophylaxis., Primary Outcome Measure: Anal HR-HPV genotypes using GeneXpert HPV assay. Fourteen HR-HPV were evaluated: HPV-16 and HPV-18/45 in 2 distinct channels and the 11 other genotypes as a pooled result (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68). The potential independent variables analysed included anal gonorrhoea and chlamydia infections, and sociodemographic and sexual behaviour factors. To assess the determinants of HR-HPV, univariate and multivariate Poisson regression models were performed by using SAS V.9.4., Results: Mean age±SD was 25.9±4.8 years. 131/204 men claimed insertive sex procured more pleasure. Thirty-two participants, accounting for 15.7% of the study sample, had gonorrhoea and/or chlamydia. The prevalence of any HR-HPV genotype was 36.3% (95% CI 30.0% to 43.0%). In total, 7.8% of men had HPV-16 and 7.4% had HPV-18/45. The prevalence for the pooled genotypes (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68) was 29.9%. Receptive anal sex during the last 6 months was strongly associated with prevalent HR-HPV infections. The adjusted proportion ratio (aPR) was 1.93 (95% CI 1.31 to 2.83). Gonorrhoea and chlamydia were also associated with the outcome of interest; p value for both infections was <0.05. The aPR comparing patients who perceived some risk of acquiring HIV to other men was 1.44 (95% CI 1.00 to 2.08)., Conclusions: In Benin, anal HR-HPV was common among HIV-negative men who have sex with men. Among this highly vulnerable population, there is a need for integrated preventive and management strategies targeting HPV and other sexually transmitted infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Intimate partner violence (IPV) may increase women's HIV acquisition risk. Still, knowledge on pathways through which IPV exacerbates HIV burden is emerging. We examined the individual and partnership-level characteristics of male perpetrators of physical and/or sexual IPV and considered their implications for women's HIV status. We pooled individual-level data from nationally representative, cross-sectional surveys in 27 countries in Africa (2000-2020) with information on past-year physical and/or sexual IPV and HIV serology among cohabiting couples (≥15 years). Current partners of women experiencing past-year IPV were assumed to be IPV perpetrators. We used Poisson regression, based on Generalized Estimating Equations, to estimate prevalence ratios (PR) for male partner and partnership-level factors associated with perpetration of IPV, and men's HIV status. We used marginal standardization to estimate the adjusted risk differences (aRD) quantifying the incremental effect of IPV on women's risk of living with HIV, beyond the risk from their partners' HIV status. Models were adjusted for survey fixed effects and potential confounders. In the 48 surveys available from 27 countries (N = 111,659 couples), one-fifth of women reported that their partner had perpetrated IPV in the past year. Men who perpetrated IPV were more likely to be living with HIV (aPR = 1.09; 95%CI: 1.01-1.16). The aRD for living with HIV among women aged 15-24 whose partners were HIV seropositive and perpetrated past-year IPV was 30% (95%CI: 26%-35%), compared to women whose partners were HIV seronegative and did not perpetrate IPV. Compared to the same group, aRD among women whose partner was HIV seropositive without perpetrating IPV was 27% (95%CI: 23%-30%). Men who perpetrated IPV are more likely to be living with HIV. IPV is associated with a slight increase in young women's risk of living with HIV beyond the risk of having an HIV seropositive partner, which suggests the mutually reinforcing effects of HIV/IPV., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JWE reports research grants from the Bill & Melinda Gates Foundation, the US National Institutes of Health, UNAIDS, WHO, and the United States Agency for International Development (USAID), personal fees from Oxford Policy Management, and support for meeting travel from UNAIDS and SACEMA, all outside the submitted work. All other authors declare no competing interests., (Copyright: © 2023 Kuchukhidze et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Epidemiological studies identified air pollution as one of the prime causes for human morbidity and mortality, due to harmful effects mainly on the cardiovascular and respiratory systems. Damage to the lung leads to several severe diseases such as fibrosis, chronic obstructive pulmonary disease and cancer. Noxious environmental aerosols are comprised of a gas and particulate phase representing highly complex chemical mixtures composed of myriads of compounds. Although some critical pollutants, foremost particulate matter (PM), could be linked to adverse health effects, a comprehensive understanding of relevant biological mechanisms and detrimental aerosol constituents is still lacking. Here, we employed a systems toxicology approach focusing on wood combustion, an important source for air pollution, and demonstrate a key role of the gas phase, specifically carbonyls, in driving adverse effects. Transcriptional profiling and biochemical analysis of human lung cells exposed at the air-liquid-interface determined DNA damage and stress response, as well as perturbation of cellular metabolism, as major key events. Connectivity mapping revealed a high similarity of gene expression signatures induced by wood smoke and agents prompting DNA-protein crosslinks (DPCs). Indeed, various gaseous aldehydes were detected in wood smoke, which promote DPCs, initiate similar genomic responses and are responsible for DNA damage provoked by wood smoke. Hence, systems toxicology enables the discovery of critical constituents of complex mixtures i.e. aerosols and highlights the role of carbonyls on top of particulate matter as an important health hazard., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Since many countries in sub-Saharan Africa are willing to implement HIV oral pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM), data are needed to assess its feasibility and relevance in real life. The study objectives were to assess drug uptake, adherence, condom use and number of sexual partners, HIV incidence and trends in the prevalence of gonorrhoea and chlamydia., Methods: In this oral PrEP demonstration study conducted prospectively in Benin, a combination of tenofovir disoproxil fumarate-TDF 300 mg and emtricitabine-FTC 200 mg (TDF-FTC) was offered daily or on-demand to MSM. Participants were recruited from 24 August to 24 November 2020 and followed over 12 months. At enrolment, month-6 and month-12, participants answered to a face-to-face questionnaire, underwent a physical examination and provided blood samples for HIV, gonorrhoea and chlamydia., Results: Overall, 204 HIV-negative men initiated PrEP. The majority of them (80%) started with daily PrEP. Retention rates at month-3, 6, 9 and 12 were 96%, 88%, 86% and 85%, respectively. At month-6 and month-12, respectively, 49% and 51% of the men on daily PrEP achieved perfect adherence (self-reported), that is seven pills taken during the last week. For event-driven PrEP, the corresponding proportions for perfect adherence (last seven at-risk sexual episodes covered) were 81% and 80%, respectively. The mean number (standard deviation) of male sexual partners over the last 6 months was 2.1 (1.70) at baseline and 1.5 (1.27) at month-12 (p-value for trend <0.001). Consistent condom use during the last 6 months was 34% (enrolment), 37% (month-6) and 36% (month-12). Three HIV seroconversions (2-daily and 1-event-driven) were recorded. Crude HIV incidence (95% confidence interval) was 1.53 (0.31-4.50)/100 person-years. Neisseria gonorrhoeae and/or Chlamydia trachomatis prevalence at the anal and/or pharyngeal and/or urethral sites was 28% at baseline and 18% at month-12 (p-value = 0.017)., Conclusions: In West Africa, oral PrEP introduction in routine practice as a component of a holistic HIV prevention package is feasible and may not result in a significant increase in condomless sex among MSM. Since HIV incidence was still higher, additional interventions, such as culturally tailored adherence counselling, may be needed to optimize the benefits of PrEP., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: In the context of universal health coverage in the Sahel, the study focuses on primary health centres and the difficulties of their implementation in the context of insurgency conflicts in central Mali., Methods: This is qualitative research through a multiple case study. We selected six health centres according to a reasoned choice to bring together contrasting situations. We conducted 96 semistructured interviews and consulted secondary quantitative data on attendance. By focusing on community health centres, the conceptual approach focuses on the process of resilience that unfolds in a dual context of chronic health system dysfunctions and armed conflict., Results: The resilience strategies deployed by health professionals were relatively basic and uncoordinated. In the end, it was the individuals who showed absorption. However, their room for manoeuvre was limited. In the most isolated health centres, resilience was based on subordinate, poorly trained staff, often from the locality. Degraded working conditions and fear caused a form of resignation among health workers., Conclusion: The strategies and resources used showed a form of minimal resilience. This form is unfolding in a context marked by two structuring features. On the one hand, the Malian health system was relatively dysfunctional before the crisis, and on the other hand, the type of conflict was relatively low intensity that allowed health centres to remain open., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many Sahel countries in Africa are looking for solutions for universal health coverage (UHC). Mali is in the process of adopting the Universal Health Insurance Plan, which allows for the mutualisation of existing schemes. Its operationalisation requires numerous adjustments to the current mutualist proposal and innovations in the system. The study focuses on innovations experienced in mutuality and their conditions of scale for UHC in Mali., Methods: This is qualitative research by multiple case studies. It is based on the collection of data by interviews (n=136), at a national and local level, on the analysis of documents (n=42) and a long field observation (7 months). The analytical framework concerns the dissemination and maintenance of health innovations (Greenhalgh et al, 2004)., Result: The analysis of this innovation shows an interest in the technical and institutional viability that determines its performance and scale-up. The procrastination and scepticism displayed at the highest level of the state and the international level, the reluctance, both financial and ideological, to renew the old mutualist proposal, penalise this Malian experiment., Conclusion: This innovation is a decisive step in ensuring the health coverage of Mali's agricultural and informal sectors. The reform will need to be amplified and supported in the future to expect the scale-up of a cheaper, technically and institutionally more efficient system. Without a political intention to mobilise national resources and accept a fundamental paradigm shift in health financing, the search for the financial viability of mutuality may, again, be at the expense of the performance., Competing Interests: Competing interests: None, (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In Mali, healthcare systems are severely affected by conflict. However, several studies suggest a lack of knowledge about its impact on maternal healthcare. Frequent and repeated attacks increase insecurity, limit access to maternal care, and thus represent a barrier to accessing care. The objective of this study is to understand how assisted deliveries are being reorganised at the health centre level, and how they are adapting to the security crisis., Method: This is a mixed sequential and explanatory study. The quantitative approaches combine a spatial scan analysis of assisted deliveries by health centres, an analysis of health centre performance using an ascending hierarchical classification, and a spatial analysis of violent events in two health districts in central Mali: Mopti and Bandiagara. The qualitative phase analyses semidirective and targeted interviews with managers (n=22) of primary healthcare centres (CsCOM) and two agents of international institutions., Results: The study reveals an important territorial heterogeneity of assisted deliveries. The primary health centres with high rates of assisted deliveries have mainly high-performance levels. This high level of use can be explained by the movement of the population to areas less exposed to attacks. The centres with low rates of assisted deliveries are those where qualified health workers refused to practice, where populations had few financial resources, and where they limited their travel to reduce their exposure to insecurity., Conclusion: This study confirms that combining methodological approaches is essential to explain significant use in the local context. The analysis of the number of assisted deliveries in conflict zones must consider the number of procedures, the nearby security context, the number of internally displaced persons and the presence of camps in which humanitarian organisations offer programmes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Extensive production and use of nanomaterials (NMs), such as titanium dioxide (TiO 2 ), raises concern regarding their potential adverse effects to humans. While considerable efforts have been made to assess the safety of TiO 2 NMs using in vitro and in vivo studies, results obtained to date are unreliable, possibly due to the dynamic agglomeration behavior of TiO 2 NMs. Moreover, agglomerates are of prime importance in occupational exposure scenarios, but their toxicological relevance remains poorly understood. Therefore, the aim of this study was to investigate the potential pulmonary effects induced by TiO 2 agglomerates of different sizes at the air-liquid interface (ALI), which is more realistic in terms of inhalation exposure, and compare it to results previously obtained under submerged conditions. A nano-TiO 2 (17 nm) and a non-nano TiO 2 (117 nm) was selected for this study. Stable stock dispersions of small agglomerates and their respective larger counterparts of each TiO 2 particles were prepared, and human bronchial epithelial (HBE) cells were exposed to different doses of aerosolized TiO 2 agglomerates at the ALI. At the end of 4h exposure, cytotoxicity, glutathione depletion, and DNA damage were evaluated. Our results indicate that dose deposition and the toxic potential in HBE cells are influenced by agglomeration and exposure via the ALI induces different cellular responses than in submerged systems. We conclude that the agglomeration state is crucial in the assessment of pulmonary effects of NMs.

Background: Benin has a long-standing history of HIV prevention programs aimed at female sex workers (FSWs). We used data from a national survey among FSWs (2017) to assess the prevention and care cascades in this population., Methods: Female sex workers were recruited through cluster sampling of sex work sites. A questionnaire was administered, and HIV tested. HIV-positive participants were asked to provide dried blood spots and were tested for antiretroviral and viral load. We assessed 2 prevention cascades (HIV testing and safer sex) and the treatment cascade, using a combination of self-reported and biological variables., Results: Mean age of the 1086 FSWs was 30 years. Half of them were Beninese, and two-thirds had a primary school education level or less. Almost all FSWs had ever heard of HIV/AIDS. More than half (79.1%) had ever been tested, and 84.1% of the latter had been tested in the last year. In the previous 6 months, 90.1% were exposed to prevention messages. Women exposed to any HIV prevention message reported a higher level of consistent condom use in the last month (69.0%) than those who were not (48.5%, P < 0.0001). HIV prevalence was 7.7%. Among HIV-positive women, 60.6% knew their status; among those, 90.5% were on antiretroviral and 81.8% of them had a suppressed viral load., Conclusions: Despite long-standing HIV prevention programs for FSWs, the prevention indicators were often low. Linkage to care was good, viral suppression was suboptimal, but knowledge of HIV-positive status was low. Exposing women to prevention messages is necessary, as to increase HIV testing., Competing Interests: Conflict of Interest and Sources of Funding: M.A. declares funding from the Canadian Institutes of Health Research (grant no. FDN-143218) for the conduction of this project and other unrelated grants from the Bill & Melinda Gates Foundation, the Public Health Agency of Canada, and the Ministère de la santé et des services sociaux du Québec. All the other authors declare no competing interests., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: HIV preexposure prophylaxis (PrEP) efficacy is closely linked to adherence, and factors associated with PrEP adherence are not well understood and may differ across populations. As PrEP demonstration projects and implementation are ongoing, it is essential to understand factors associated with adherence to oral PrEP to design effective adherence interventions and maximize the public health impact of PrEP. We thus aimed to assess demographic and behavioral factors associated with optimal PrEP adherence (100%) among female sex workers (FSWs) participating in a demonstration project in Cotonou, Benin., Methods: Female sex workers were provided with daily Truvada and followed quarterly for 1 to 2 years. Sociodemographics, partners, and behaviors were collected through face-to-face questionnaires. Another questionnaire based on sexual the theory of planned behavior and the theory of interpersonal behavior was also administered. Generalized estimating equations were used to identify factors associated with optimal daily adherence., Results: At baseline, 255 FSWs were followed up. One-year increase in age of FSWs was associated with a 3% increase in optimal adherence (prevalence ratio, 1.03; 95% confidence interval, 1.01-1.05; P for trend = 0.0003), and optimal adherence decreased by 31% for every 6 months of follow-up (prevalence ratio, 0.69; 95% confidence interval, 0.59-0.79; P for trend < 0.0001). For the participants who have completed the behavioral questionnaires, high intention to adhere to the treatment was also a predictor of optimal adherence., Conclusions: Efforts should be geared toward FSWs intending to use PrEP to help them reach adequate adherence levels for effective HIV protection., Competing Interests: Conflict of Interest and Sources of Funding: The authors declare no conflict of interest. This study was funded by the Bill and Melinda Gates Foundation (grant no. OPP1098973). Complementary funding was provided by the Canadian Institutes of Health Research (grant numbers ROH-115205 and FDN-143218). Truvada for preexposure prophylaxis was provided free of charge by Gilead Sciences, Inc. The views expressed herein are those of the authors and do not necessarily reflect the official policy or position of the Bill & Melinda Gates Foundation., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Background: The COVID-19 pandemic indirectly impacts HIV epidemiology in Central/West Africa. We estimated the potential impact of COVID-19-related disruptions to HIV prevention/treatment services and sexual partnerships on HIV incidence and HIV-related deaths among key populations including female sex workers (FSW), their clients, men who have sex with men, and overall., Setting: Yaoundé (Cameroon) and Cotonou (Benin)., Methods: We used mathematical models of HIV calibrated to city population-specific and risk population-specific demographic/behavioral/epidemic data. We estimated the relative change in 1-year HIV incidence and HIV-related deaths for various disruption scenarios of HIV prevention/treatment services and decreased casual/commercial partnerships, compared with a scenario without COVID-19., Results: A 50% reduction in condom use in all partnerships over 6 months would increase 1-year HIV incidence by 39%, 42%, 31%, and 23% among men who have sex with men, FSW, clients, and overall in Yaoundé, respectively, and 69%, 49%, and 23% among FSW, clients, and overall, respectively, in Cotonou. Combining a 6-month interruption of ART initiation and 50% reduction in HIV prevention/treatment use would increase HIV incidence by 50% and HIV-related deaths by 20%. This increase in HIV infections would be halved by a simultaneous 50% reduction in casual and commercial partnerships., Conclusions: Reductions in condom use after COVID-19 would increase infections among key populations disproportionately, particularly FSW in Cotonou, who need uninterrupted condom provision. Disruptions in HIV prevention/treatment services have the biggest impacts on HIV infections and deaths overall, only partially mitigated by equal reductions in casual/commercial sexual partnerships. Maintaining ART provision must be prioritized to minimize short-term excess HIV-related deaths., Competing Interests: K.M.M. has received an honorarium from Gilead for speaking, outside the submitted work. The remaining authors have conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Daily pre-exposure prophylaxis (PrEP) and treatment-as-prevention (TasP) reduce HIV acquisition and transmission risk, respectively. A demonstration study (2015-2017) assessed TasP and PrEP feasibility among female sex workers (FSW) in Cotonou, Benin., Setting: Cotonou, Benin., Methods: We developed a compartmental HIV transmission model featuring PrEP and antiretroviral therapy (ART) among the high-risk (FSW and clients) and low-risk populations, calibrated to historical epidemiological and demonstration study data, reflecting observed lower PrEP uptake, adherence and retention compared with TasP. We estimated the population-level impact of the 2-year study and several 20-year intervention scenarios, varying coverage and adherence independently and together. We report the percentage [median, 2.5th-97.5th percentile uncertainty interval (95% UI)] of HIV infections prevented comparing the intervention and counterfactual (2017 coverages: 0% PrEP and 49% ART) scenarios., Results: The 2-year study (2017 coverages: 9% PrEP and 83% ART) prevented an estimated 8% (95% UI 6-12) and 6% (3-10) infections among FSW over 2 and 20 years, respectively, compared with 7% (3-11) and 5% (2-9) overall. The PrEP and TasP arms prevented 0.4% (0.2-0.8) and 4.6% (2.2-8.7) infections overall over 20 years, respectively. Twenty-year PrEP and TasP scale-ups (2035 coverages: 47% PrEP and 88% ART) prevented 21% (17-26) and 17% (10-27) infections among FSW, respectively, and 5% (3-10) and 17% (10-27) overall. Compared with TasP scale-up alone, PrEP and TasP combined scale-up prevented 1.9× and 1.2× more infections among FSW and overall, respectively., Conclusions: The demonstration study impact was modest, and mostly from TasP. Increasing PrEP adherence and coverage improves impact substantially among FSW, but little overall. We recommend TasP in prevention packages., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Reliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays. However, there is still a need for rigorous side-by-side comparisons of the results obtained with the two different exposure methods considering numerous parameters, such as different MNMs, cell culture models and read outs. In this study, human A549 lung epithelial cells and differentiated THP-1 macrophages were exposed under submerged conditions to two abundant types of MNMs i.e., ceria and titania nanoparticles (NPs). Membrane integrity, metabolic activity as well as pro-inflammatory responses were recorded. For comparison, A549 monocultures were also exposed at the ALI to the same MNMs. In the case of titania NPs, genotoxicity was also investigated. In general, cells were more sensitive at the ALI compared to under classical submerged conditions. Whereas ceria NPs triggered only moderate effects, titania NPs clearly initiated cytotoxicity, pro-inflammatory gene expression and genotoxicity. Interestingly, low doses of NPs deposited at the ALI were sufficient to drive adverse outcomes, as also documented in rodent experiments. Therefore, further development of ALI systems seems promising to refine, reduce or even replace acute pulmonary toxicity studies in animals.

Background: In Benin, men who have sex with men (MSM) do not always use condoms during anal sex. Pre-exposure prophylaxis (PrEP) using Truvada® (tenofovir disoproxil fumarate / emtricitabine) may be a complementary HIV prevention measure for MSM. This study aimed at identifying the potential facilitators and barriers to the use of PrEP., Methods: This was a cross-sectional study conducted in 2018 among male-born MSM aged 18 years or older who reported being HIV-negative or unaware of their HIV status. The participants were recruited by the RDS technique (respondent driven sampling) in six cities of Benin. Logistic regression analyses, adapted to RDS statistical requirements, were performed to identify the factors associated with PrEP acceptability., Results: Mean age of the 400 MSM recruited was 26.2 ± 5.0 years. PrEP was known by 50.7% of respondents. The intention to use PrEP was expressed by 90% of MSM. If PrEP effectiveness were 90% or more, 87.8% of the respondents thought they would decrease condom use. In multivariate analysis, the facilitators associated with PrEP acceptability were: not having to pay for PrEP (odds ratio (OR) = 2.39, 95% CI: 1.50-4.46) and its accessibility within MSM networks (OR = 9.82, 95% CI: 3.50-27.52). Only one barrier was significant: the concern that taking PrEP be perceived as marker of adopting HIV risky behaviors (OR = 0.11, 95% CI: 0.04-0.30)., Conclusion: In Benin, not all MSM know about PrEP. But once well informed, the majority seems willing to use it if made available. The free availability of the drug and its accessibility in the MSM networks are important facilitators. The possibility of decrease in condom use should not be a barrier to the prescription of PrEP if made available.

The quality and relevance of nanosafety studies constitute major challenges to ensure their key role as a supporting tool in sustainable innovation, and subsequent competitive economic advantage. However, the number of apparently contradictory and inconclusive research results has increased in the past few years, indicating the need to introduce harmonized protocols and good practices in the nanosafety research community. Therefore, we aimed to evaluate if best-practice training and inter-laboratory comparison (ILC) of performance of the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay for the cytotoxicity assessment of nanomaterials among 15 European laboratories can improve quality in nanosafety testing. We used two well-described model nanoparticles, 40-nm carboxylated polystyrene (PS-COOH) and 50-nm amino-modified polystyrene (PS-NH2). We followed a tiered approach using well-developed standard operating procedures (SOPs) and sharing the same cells, serum and nanoparticles. We started with determination of the cell growth rate (tier 1), followed by a method transfer phase, in which all laboratories performed the first ILC on the MTS assay (tier 2). Based on the outcome of tier 2 and a survey of laboratory practices, specific training was organized, and the MTS assay SOP was refined. This led to largely improved intra- and inter-laboratory reproducibility in tier 3. In addition, we confirmed that PS-COOH and PS-NH2 are suitable negative and positive control nanoparticles, respectively, to evaluate impact of nanomaterials on cell viability using the MTS assay. Overall, we have demonstrated that the tiered process followed here, with the use of SOPs and representative control nanomaterials, is necessary and makes it possible to achieve good inter-laboratory reproducibility, and therefore high-quality nanotoxicological data.

Background: Preventive chemotherapy with praziquantel is the cornerstone of schistosomiasis control. However, in some social-ecological settings, the prevalence and/or intensity of Schistosoma infection does not lower meaningfully despite multiple rounds of preventive chemotherapy, a phenomenon termed persistent hotspot (PHS). We assessed the characteristics of PHS in a Schistosoma mansoni-endemic area of Côte d'Ivoire., Methods: In October 2016, a cross-sectional survey was conducted in 14 schools in the western part of Côte d'Ivoire, one year after multiple rounds of preventive chemotherapy. In each school, 50 children aged 9-12 years provided two stool samples and one urine sample. Stool samples were subjected to triplicate Kato-Katz thick smears for S. mansoni diagnosis. Urine samples were examined by a filtration method for S. haematobium eggs. PHS was defined as failure to achieve a reduction in the prevalence of S. mansoni infection of at least 35% and/or a reduction of infection intensity of at least 50%. Six schools underwent more detailed investigations, including a questionnaire survey for demographic characteristics and a malacological survey., Results: In the six schools subjected to detailed investigations, the overall prevalence of S. mansoni and S. haematobium was 9.5% and 2.6%, respectively. Four schools were classified as PHS. The S. mansoni prevalence in the four PHS was 10.9% compared to 6.6% in the remaining two schools. The S. mansoni infection intensity, expressed as arithmetic mean eggs per gram of stool (EPG) among infected children, was 123.8 EPG in PHS and 18.7 EPG in the other two schools. Children bathing in open freshwater bodies were at higher odds of S. mansoni infection (odds ratio: 4.5, 95% confidence interval: 1.6-12.6). A total of 76 human-water contact sites (53 in PHS and 23 in the other schools) were examined and 688 snails were collected, including potential intermediate host snails of Schistosoma (Biomphalaria pfeifferi, Bulinus forskalii, Bu. globosus and Bu. truncatus)., Conclusion: Children in PHS schools bathed more frequently in open freshwater bodies, and hence, they are more exposed to Schistosoma transmission. Our findings call for an integrated control approach, complementing preventive chemotherapy with other interventions, particularly in PHS settings.

Background: Measuring adherence to PrEP (pre-exposure prophylaxis) remains challenging. Biological adherence measurements are reported to be more accurate than self-reports and pill counts but can be expensive and not suitable on a daily basis in resource-limited countries. Using data from a demonstration project on PrEP among female sex workers in Benin, we aimed to measure adherence to PrEP and compare self-report and pill count adherence to tenofovir (TFV) disoproxil fumarate (TDF) concentration in plasma to determine if these 2 measures are reliable and correlate well with biological adherence measurements., Methods: Plasma TFV concentrations were analyzed in samples collected at day 14 follow-up visit and months 6, 12, 18, and 24 (or at last visit when follow-up was shorter). Self-reported adherence was captured at day 14 follow-up visit and then quarterly by asking participants to report the number of missed pills within the last week. For pill count, medications were refilled monthly and participants were asked to bring in their medication bottles at each follow-up visit. Using generalized estimating equations adherence measured by self-report and pill count was compared to plasma drug concentrations., Results: Of 255 participants, 47.1% completed follow-up. Weighted optimal adherence combining data from all visits was 26.8% for TFV concentration, 56.0% by self-report and 18.9% by pill count. Adherence measured by both TFV concentrations and self-report decreased over time (P = .009 and P = .019, respectively), while the decreasing trend in adherence by pill count was not significant (P = .087). The decrease in adherence was greater using TFV concentrations than the other 2 adherence measures., Conclusion: With high levels of misreporting of adherence using self-report and pill count, the objective biomedical assessment of adherence via laboratory testing is optimal and more accurately reflects PrEP uptake and persistence. Alternative inexpensive and accurate approaches to monitor PrEP adherence should be investigated.

Objectives: Female sex workers (FSWs) play a key role in HIV transmission in West Africa, while they have limited access to antiretroviral therapy (ART). In line with UNAIDS recommendations extending ART to all HIV-infected individuals, we conducted this demonstration project on immediate treatment as prevention (TasP) among FSWs in Cotonou, Benin. We report data on treatment response and its relation to adherence, as well as on ART-resistant genotypes., Methods: Complete follow-up varied between 12 and 24 months. At each three-monthly visit, a questionnaire was administered, clinical examinations were carried out and blood samples collected. Adherence to treatment was estimated by self-report. Viral RNA was genotyped at baseline and final visits for drug resistance. Generalized estimating equations for repeated measures with a log-binomial link were used to analyze time trends and the association between adherence and virological response to treatment., Results: One-hundred-seven HIV-positive and ART-naive FSWs were enrolled; 59.8% remained in the cohort till study completion and 62.6% had a final visit. Viral load<1000 (below quantification limit [<50]) was attained in 73.1% (64.6%) of participants at month-6, 84.8% (71.2%) at month-12, and 80.9% (65.1%) at the final visit. The proportion of women with suppressed (below quantification limit) viral load increased with increasing self-reported adherence (p = 0.06 (0.003), tests for trend). The proportion of participants with CD4≤500 also decreased drastically throughout follow-up (p < .0001). Twelve participants exhibited ART-resistant genotypes at baseline, but only two at their final visit., Conclusion: Our findings indicate that TasP is widely accepted among FSWs in Cotonou and could be implemented with relative success. However, due to mobility in this population, follow-up was sub-optimal, suggesting that large geographical coverage of FSW-friendly clinics is needed for sustained treatment implementation. We also fell short of the UNAIDS objective of 90% viral suppression among treated patients, underlining the need for better adherence support programs., Competing Interests: SD Bioline HIV/Syphilis duo test was provided free of charge by Standard Diagnostics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Several in vitro studies have suggested that silica nanoparticles (NPs) might induce adverse effects in gut cells. Here, we used the human colon cancer epithelial cell line HCT116 to study the potential cytotoxic effects of ingested silica NPs in the presence or absence of serum. Furthermore, we evaluated different physico-chemical parameters important for the assessment of nanoparticle safety, including primary particle size (12, 70, 200, and 500 nm) and surface modification (-NH 2 and -COOH). Silica NPs triggered cytotoxicity, as evidenced by reduced metabolism and enhanced membrane leakage. Automated microscopy revealed that the silica NPs promoted apoptosis and necrosis proportional to the administered specific surface area dose. Cytotoxicity of silica NPs was suppressed by increasing amount of serum and surface modification. Furthermore, inhibition of caspases partially prevented silica NP-induced cytotoxicity. In order to investigate the role of specific cell death pathways in more detail, we used isogenic derivatives of HCT116 cells which lack the pro-apoptotic proteins p53 or BAX. In contrast to the anticancer drug cisplatin, silica NPs induced cell death independent of the p53-BAX axis. In conclusion, silica NPs initiated cell death in colon cancer cells dependent on the specific surface area and presence of serum. Further studies in vivo are warranted to address potential cytotoxic actions in the gut epithelium. The unintended toxicity of silica NPs as observed here could also be beneficial. As loss of p53 in colon cancer cells contributes to resistance against anticancer drugs, and thus to reoccurrence of colon cancer, targeted delivery of silica NPs could be envisioned to also deplete p53 deficient tumor cells.

Background: Despite Côte d'Ivoire epidemic being labeled as "generalized," key populations (KPs) are important to overall transmission. Using a dynamic model of HIV transmission, we previously estimated the impact of several treatment-as-prevention strategies that reached-or missed-the UNAIDS 90-90-90 targets in different populations groups, including KP and clients of female sex workers (CFSWs). To inform program planning and resources allocation, we assessed the cost-effectiveness of these scenarios., Methods: Costing was performed from the provider's perspective. Unit costs were obtained from the Ivorian Programme national de lutte contre le Sida (USD 2015) and discounted at 3%. Net incremental cost-effectiveness ratios (ICER) per adult HIV infection prevented and per disability-adjusted life-years (DALY) averted were estimated over 2015-2030., Results: The 3 most cost-effective and affordable scenarios were the ones that projected current programmatic trends [ICER = $210; 90% uncertainty interval (90% UI): $150-$300], attaining the 90-90-90 objectives among KP and CFSW (ICER = $220; 90% UI: $80-$510), and among KP only (ICER = $290; 90% UI: $90-$660). The least cost-effective scenario was the one that reached the UNAIDS 90-90-90 target accompanied by a 25% point drop in condom use in KP (ICER = $710; 90% UI: $450-$1270). In comparison, the UNAIDS scenario had a net ICER of $570 (90% UI: $390-$900) per DALY averted., Conclusions: According to commonly used thresholds, accelerating the HIV response can be considered very cost-effective for all scenarios. However, when balancing epidemiological impact, cost-effectiveness, and affordability, scenarios that sustain both high condom use and rates of viral suppression among KP and CFSW seem most promising in Côte d'Ivoire.

Background: MDR-TB is a major threat to global TB control. In 2015, 580,000 were treated for MDR-TB worldwide. The worldwide roll-out of GeneXpert MTB/RIF ® has improved diagnosis of MDR-TB; however, in many countries laboratories are unable to assess drug resistance and clinical predictors of MDR-TB could help target suspected patients. In this study, we aimed to determine the clinical factors associated with MDR-TB in Bamako, Mali., Methods: We performed a cross-sectional study of 214 patients with presumed MDR-TB admitted to University of Bamako Teaching Hospital, Point-G between 2007 and 2016. We calculated crude and adjusted odds ratios for MDR-TB disease diagnosis using SPSS., Results: We found that age ≤40years (OR=2.56. 95% CI: 1.44-4.55), two courses of prior TB treatment (OR=3.25, 95% CI: 1.44-7.30), TB treatment failure (OR=3.82, 95% CI 1.82-7.79), sputum microscopy with 3+ bacilli load (OR=1.98, 95% CI: 1.13-3.48) and a history of contact with a TB patient (OR=2.48, 95% CI: 1.11-5.50) were significantly associated with confirmation of MDR-TB disease. HIV was not a risk factor for MDR-TB (aOR=0.88, 95% CI: 0.34-1.94)., Conclusion: We identified several risk factors that could be used to identify MDR-TB suspects and prioritize them for laboratory confirmation. Prospective studies are needed to understand factors associated with TB incidence and clinical outcomes of TB treatment and disease., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Particokinetic models are important to predict the effective cellular dose, which is key to understanding the interactions of particles with biological systems. For the reliable establishment of dose-response curves in, e.g., the field of pharmacology and toxicology, mostly the In vitro Sedimentation, Diffusion and Dosimetry (ISDD) and Distorted Grid (DG) models have been employed. Here, we used high resolution scanning electron microscopy to quantify deposited numbers of particles on cellular and intercellular surfaces and compare experimental findings with results predicted by the ISDD and DG models., Results: Exposure of human lung epithelial A549 cells to various concentrations of differently sized silica particles (100, 200 and 500 nm) revealed a remarkably higher dose deposited on intercellular regions compared to cellular surfaces. The ISDD and DG models correctly predicted the areal densities of particles in the intercellular space when a high adsorption ("stickiness") to the surface was emulated. In contrast, the lower dose on cells was accurately inferred by the DG model in the case of "non-sticky" boundary conditions. Finally, the presence of cells seemed to enhance particle deposition, as aerial densities on cell-free substrates were clearly reduced., Conclusions: Our results further validate the use of particokinetic models but also demonstrate their limitations, specifically, with respect to the spatial distribution of particles on heterogeneous surfaces. Consideration of surface properties with respect to adhesion and desorption should advance modelling approaches to ultimately predict the cellular dose with higher precision.

Introduction: In sub-Saharan Africa, HIV prevalence remains high, especially among key populations. In such situations, combination prevention including clinical, behavioural, structural and biological components, as well as adequate treatment are important. We conducted a demonstration project at the Dispensaire IST, a clinic dedicated to female sex workers (FSWs) in Cotonou, on early antiretroviral therapy (E-ART, or immediate "test-and-treat") and pre-exposure prophylaxis (PrEP). We present key indicators such as uptake, retention and adherence., Methods: In this prospective observational study, we recruited FSWs from October 4th 2014 to December 31st 2015 and followed them until December 31st 2016. FSWs were provided with daily tenofovir disoproxil fumarate/emtricitabine (Truvada ® ) for PrEP or received a first-line antiretroviral regimen as per Benin guidelines. We used generalized estimating equations to assess trends in adherence and sexual behaviour., Results: Among FSWs in the catchment area, HIV testing coverage within the study framework was 95.5% (422/442). At baseline, HIV prevalence was 26.3% (111/422). Among eligible FSWs, 95.5% (105/110) were recruited for E-ART and 88.3% (256/290) for PrEP. Overall retention at the end of the study was 59.0% (62/105) for E-ART and 47.3% (121/256) for PrEP. Mean (±SD) duration of follow-up was 13.4 (±7.9) months for E-ART and 11.8 (±7.9) months for PrEP. Self-reported adherence was over 90% among most E-ART participants. For PrEP, adherence was lower and the proportion with 100% adherence decreased over time from 78.4% to 56.7% (p-trend < 0.0001). During the 250.1 person-years of follow-up among PrEP initiators, two seroconversions occurred (incidence 0.8/100 person-years (95% confidence interval: 0.3 to 1.9/100 person-years)). The two seroconverters had stopped using PrEP for at least six months before being found HIV-infected. In both groups, there was no evidence of reduced condom use., Conclusions: This study provides data on key indicators for the integration of E-ART and PrEP into the HIV prevention combination package already offered to FSWs in Benin. PrEP may be more useful as an individual intervention for adherent FSWs rather than a specific public health intervention. E-ART was a more successful intervention in terms of retention and adherence and is now offered to all key populations in Benin., Study Registration: ClinicalTrials.gov NCT02237., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Female sex workers (FSWs) continue to carry a heavy burden of sexually transmitted infections (STI). For prevention purposes, there is a need to identify most-at-risk subgroups among them. The objective of this longitudinal cohort study conducted at Dispensaire IST, Cotonou, Benin, was to assess Neisseria gonorrhoeae (NG) / Chlamydia trachomatis (CT) incidence and determinants; and HIV incidence among FSWs in presence of STI/HIV risk reduction activities. Overall, 319 adult FSWs were followed quarterly from September 2008 to March 2012. NG/CT were detected from endocervical swabs by Amplified DNA Assays employing Strand displacement amplification technology. HIV testing was done on capillary blood using two consecutive rapid diagnostic tests. Anderson-Gill proportional hazard models (HR) were used to determine factors independently associated with NG/CT incidence. The majority of FSWs were HIV-negative (188, 58.9%). There were 6 HIV seroconversions among these 188 HIV-negative women. HIV incidence (95% Confidence interval, CI) was 1.41 (0.28-2.54) seroconversions per 100 person-years at risk (PYAR): 6 events / 425.1 PYAR. Sixty-two out of 319 women experienced 83 new episodes of NG/CT for an overall incidence rate (95% CI) of 10.8 (8.17-13.88) events / 100 PYAR. From month-24 onwards, HIV-positive women (treated: HR (95%CI): 4.2 (1.60-10.77); untreated: HR (95%CI): 4.2 (1.59-11.49) were more likely to acquire NG/CT compared to HIV-negative FSWs. Longer duration in sex work (>2 years: HR; 95%CI: 0.4 (0.22-0.72)) was protective against NG/CT. Refusal by clients (55.8%) was the main reason for non-condom use. Enrolling women from one clinic (Dispensaire IST) may have impaired generalizability of the findings. New NG/CT/HIV infections were observed among FSWs notwithstanding ongoing prevention interventions. To eliminate HIV transmission among FSWs, STI/HIV control programs need to promote women's empowerment and address vulnerability to infection of HIV-positive FSWs.

A central challenge for the safe design of nanomaterials (NMs) is the inherent variability of NM properties, both as produced and as they interact with and evolve in, their surroundings. This has led to uncertainty in the literature regarding whether the biological and toxicological effects reported for NMs are related to specific NM properties themselves, or rather to the presence of impurities or physical effects such as agglomeration of particles. Thus, there is a strong need for systematic evaluation of the synthesis and processing parameters that lead to potential variability of different NM batches and the reproducible production of commonly utilized NMs. The work described here represents over three years of effort across 14 European laboratories to assess the reproducibility of nanoparticle properties produced by the same and modified synthesis routes for four of the OECD priority NMs (silica dioxide, zinc oxide, cerium dioxide and titanium dioxide) as well as amine-modified polystyrene NMs, which are frequently employed as positive controls for nanotoxicity studies. For 46 different batches of the selected NMs, all physicochemical descriptors as prioritized by the OECD have been fully characterized. The study represents the most complete assessment of NMs batch-to-batch variability performed to date and provides numerous important insights into the potential sources of variability of NMs and how these might be reduced.

Current evidence suggests that anal intercourse (AI) during sex work is common in sub-Saharan Africa, but there have been few studies in which the contribution of heterosexual AI to human immunodeficiency virus (HIV) epidemics has been investigated. Using a respondent-driven sampling survey of female sex workers (FSWs; n = 466) in Abidjan, Côte d'Ivoire, in 2014, we estimated AI prevalence and frequency. Poisson regressions were used to identify AI determinants. Approximately 20% of FSWs engaged in AI during a normal week (95% confidence interval: 15, 26). Women who performed AI were generally younger, had been selling sex for longer, were born in Côte d'Ivoire, and reported higher sex-work income, more frequent sex in public places, and violence from clients than women not reporting AI. Condom use was lower, condom breakage/slippage more frequent, and use of water-based lubricants was less frequently reported for AI than for vaginal intercourse. Using a dynamic transmission model, we estimated that 22% (95% credible interval: 11, 37% of new HIV infections could have been averted among FSWs during 2000-2015 if AI had been substituted for vaginal intercourse. Despite representing a small fraction of all sex acts, AI is an underestimated source of HIV transmission. Increasing availability and uptake of condoms, lubricants, and pre-exposure prophylaxis for women engaging in AI could help mitigate HIV risk., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Understanding the impact of past interventions and how it affected transmission dynamics is key to guiding prevention efforts. We estimated the population-level impact of condom, antiretroviral therapy (ART), and prevention of mother-to-child transmission activities on HIV transmission and the contribution of key risk factors on HIV acquisition and transmission., Methods: An age-stratified dynamical model of sexual and vertical HIV transmission among the general population, female sex workers (FSW), and men who have sex with men was calibrated to detailed prevalence and intervention data. We estimated the fraction of HIV infections averted by the interventions, and the fraction of incident infections acquired and transmitted by different populations over successive 10-year periods (1976-2015)., Results: Overall, condom use averted 61% (95% credible intervals: 56%-66%) of all adult infections during 1987-2015 mainly because of increased use by FSW (46% of infections averted). In comparison, ART prevented 15% (10%-19%) of adult infections during 2010-2015. As a result, FSW initially (1976-1985) contributed 95% (91%-97%) of all new infections, declining to 19% (11%-27%) during 2005-2015. Older men and clients mixing with non-FSW are currently the highest contributors to transmission. Men who have sex with men contributed ≤4% transmissions throughout. Young women (15-24 years; excluding FSW) do not transmit more infections than they acquired., Conclusions: Early increases in condom use, mainly by FSW, have substantially reduced HIV transmission. Clients of FSWs and older men have become the main source of transmission, whereas young women remain at increased risk. Strengthening prevention and scaling-up of ART, particularly to FSW and clients of female sex workers, is important.

All over the world, different types of nanomaterials with a diversified spectrum of applications are designed and developed, especially in the field of nanomedicine. The great variety of nanoparticles (NPs), in vitro test systems and cell lines led to a vast amount of publications with conflicting data. To identify the decisive principles of these variabilities, we conducted an intercomparison study of collaborating laboratories within the German DFG Priority Program SPP1313, using well-defined experimental parameters and well-characterized NPs. The participants analyzed the in vitro biocompatibility of silica and polymer NPs on human hepatoma HepG2 cells. Nanoparticle mediated effects on cell metabolism, internalization, and inflammation were measured. All laboratories showed that both nanoparticle formulations were internalized and had a low cytotoxicity profile. Interestingly, small variations in nanoparticle preparation, cell handling and the type of culture slide influenced the nanoparticle stability and the outcomes of cell assays. The round robin test demonstrated the importance of the use of clearly defined and characterized NPs and parameters for reproducible results across laboratories. Comparative analyses of in vitro screening methods performed in multiple laboratories are absolutely essential to establish robust standard operation procedure as a prerequisite for sound hazard assessment of nanomaterials.

Background: National responses will need to be markedly accelerated to achieve the ambitious target of the Joint United Nations Programme on HIV/AIDS (UNAIDS). This target aims for 90% of HIV-positive individuals to be aware of their status, for 90% of those aware to receive antiretroviral therapy (ART), and for 90% of those on treatment to have a suppressed viral load by 2020, with each individual target reaching 95% by 2030. We aimed to estimate the impact of various treatment-as-prevention scenarios in Côte d'Ivoire, one of the countries with the highest HIV incidence in West Africa, with unmet HIV prevention and treatment needs, and where key populations are important to the broader HIV epidemic., Methods and Findings: An age-stratified dynamic model was developed and calibrated to epidemiological and programmatic data using a Bayesian framework. The model represents sexual and vertical HIV transmission in the general population, female sex workers (FSW), and men who have sex with men (MSM). We estimated the impact of scaling up interventions to reach the UNAIDS targets, as well as the impact of 8 other scenarios, on HIV transmission in adults and children, compared to our baseline scenario that maintains 2015 rates of testing, ART initiation, ART discontinuation, treatment failure, and levels of condom use. In 2015, we estimated that 52% (95% credible intervals: 46%-58%) of HIV-positive individuals were aware of their status, 72% (57%-82%) of those aware were on ART, and 77% (74%-79%) of those on ART were virologically suppressed. Reaching the UNAIDS targets on time would avert 50% (42%-60%) of new HIV infections over 2015-2030 compared to 30% (25%-36%) if the 90-90-90 target is reached in 2025. Attaining the UNAIDS targets in FSW, their clients, and MSM (but not in the rest of the population) would avert a similar fraction of new infections (30%; 21%-39%). A 25-percentage-point drop in condom use from the 2015 levels among FSW and MSM would reduce the impact of reaching the UNAIDS targets, with 38% (26%-51%) of infections averted. The study's main limitation is that homogenous spatial coverage of interventions was assumed, and future lines of inquiry should examine how geographical prioritization could affect HIV transmission., Conclusions: Maximizing the impact of the UNAIDS targets will require rapid scale-up of interventions, particularly testing, ART initiation, and limiting ART discontinuation. Reaching clients of FSW, as well as key populations, can efficiently reduce transmission. Sustaining the high condom-use levels among key populations should remain an important prevention pillar.

Nanostructured silica particles are commonly used in biomedical and biotechnical fields, as well as, in cosmetics and food industry. Thus, their environmental and health impacts are of great interest and effects after oral uptake are only rarely investigated. In the present study, the toxicological effects of commercially available nano-scaled silica with a nominal primary diameter of 12 nm were investigated on the human gastric carcinoma cell line GXF251L. Besides the analysis of cytotoxic and proliferative effects and the comparison with effects of particles with a nominal primary diameter of 200 nm, emphasis was also given to their influence on the cellular epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) signaling pathways-both of them deeply involved in the regulation of cellular processes like cell cycle progression, differentiation or proliferation. The investigated silica nanoparticles (NPs) were found to stimulate cell proliferation as measured by microscopy and the sulforhodamine B assay. In accordance, the nuclear level of the proliferation marker Ki-67 was enhanced in a concentration-dependent manner. At high particle concentrations also necrosis was induced. Finally, silica NPs affected the EGFR and MAPK pathways at various levels dependent on concentration and time. However, classical activation of the EGFR, to be reflected by enhanced levels of phosphorylation, could be excluded as major trigger of the proliferative stimulus. After 45 min of incubation the level of phosphorylated EGFR did not increase, whereas enhanced levels of total EGFR protein were observed. These results indicate interference with the complex homeostasis of the EGFR protein, whereby up to 24 h no impact on the transcription level was detected. In addition, downstream on the level of the MAP kinases ERK1/2 short term incubation appeared to affect total protein levels without clear increase in phosphorylation. Depending on the concentration range, enhanced levels of ERK1/2 phosphorylation were only observed after 24 h of incubation. Taken together, the present study demonstrates the potential of the tested silica particles to enhance the growth of gastric carcinoma cells. Although interference with the EGFR/MAPK cascade is observed, additional mechanisms are likely to be involved in the onset of the proliferative stimulus.