Breast cancer treatment and its impact on survival in Morocco: a study over a decade.

BACKGROUND: In Morocco, much progress has been made in breast cancer treatment. However, there is limited information on survival outcomes of breast cancer patients according to their therapeutic management. METHODS: A pattern-of-care study was conducted in Morocco's two main oncology centres: Rabat and Casablanca and has shown that major progress has been made in the quality of care with survival rates comparable to those in developed countries. The present study focuses on the different therapeutic strategies used in breast cancer and their impact on prognosis. Patients were classified into two categories: those considered as appropriately managed and those who were not. RESULTS: A total of 1901 women with stage I to III breast cancer were included in this study, the majority (53%) were adequately managed and had better disease-free survival (DFS) rates than those who were not: DFS at 3 years (88% versus 62%) and at 5 years (80% versus 50%). Potential significant determinants of better management were: treatment in Rabat's oncology centre, treatment between 2008 and 2012, being aged younger than 60 years, and early TN stage. CONCLUSION: This study demonstrated the value of proper integrated and coordinated management in a comprehensive cancer centre, to improve breast cancer survival.

LLIN Evaluation in Uganda Project (LLINEUP)-effects of a vector control trial on Plasmodium infection prevalence and genotypic markers of insecticide resistance in Anopheles vectors from 48 districts of Uganda.

Pyrethroid bednets treated with the synergist piperonyl butoxide (PBO) offer the possibility of improved vector control in mosquito populations with metabolic resistance. In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus PBO (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, we conducted cross-sectional household entomological surveys at baseline and then every 6 months for two years, which we use here to investigate longitudinal changes in mosquito infection rate and genetic markers of resistance. Overall, 5395 female Anopheles mosquitoes were collected from 5046 households. The proportion of mosquitoes infected (PCR-positive) with Plasmodium falciparum did not change significantly over time, while infection with non-falciparum malaria decreased in An. gambiae s.s., but not An. funestus. The frequency of genetic markers associated with pyrethroid resistance increased significantly over time, but the rate of change was not different between the two LLIN types. The knock-down resistance (kdr) mutation Vgsc-995S declined over time as Vgsc-995F, the alternative resistance mutation at this codon, increased. Vgsc-995F appears to be spreading into Uganda. Distribution of LLINs in Uganda was previously found to be associated with reductions in parasite prevalence and vector density, but here we show that the proportion of infective mosquitoes remained stable across both PBO and non-PBO LLINs, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors and highlights the potential benefits of resistance management strategies.Trial registration: This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395 .

Impact of CBE-based screening program on care pathway, stage at diagnosis, nature of treatment, and overall survival among breast cancer patients in Morocco.

BACKGROUND: This study aimed to indirectly examine whether the implementation of clinical breast examination-based screening program in Morocco has been successful in downstaging and improving survival rates. Breast cancer patients detected through the screening pathway were compared with those detected through self-referral over the same period in terms of cancer stage at diagnosis, tumor characteristics, care delays, and survival. METHODS: A prospective observational study was conducted between April 2019 and August 2020 at two major public oncology centers. RESULTS: A total of 896 women with confirmed breast cancer were recruited (483 were program-referred and 413 were self-referred). The authors did not report any significant difference between the two groups in terms of stage at diagnosis, molecular profile, or histopathological grade. Early-stage cancer (stage I-II) was detected in 55.7% of self-referred participants compared to 55.5% of program-referred participants. Median intervals between symptom recognition, pathological diagnosis, and treatment initiation were not significantly different between the two groups. Similarly, survival after treatment showed no significant difference between patients screened by the program and self-referred patients. The 3-year survival rate after treatment was 94.5% for patients referred through the program and 88.6% for patients not referred through the program (p = .16). CONCLUSIONS: This study highlights the importance of equitable and timely access to high-quality diagnosis and treatment facilities, leading to substantial downstaging and enhanced survival rates. Continued efforts to improve quality and expand coverage to include asymptomatic women will consolidate the health infrastructure gains achieved by the Moroccan breast cancer screening program.

Epidemiologic Trends of Cleft Lip and Palate in a Southern State: A 30-Year Follow-Up.

OBJECTIVES: Children's of Mississippi at the University of Mississippi Medical Center serves as the state's only American Cleft Palate-Craniofacial Association-approved cleft team at the only pediatric hospital in the state. The goal of this study is to report geographic and demographic patterns of patients with orofacial cleft (OFC) treated at Children's of Mississippi, which are lacking. METHODS: Patients with OFC treated at Children's of Mississippi from 2015 to 2020 were included. Demographic data were collected, including birth county and total live births from state data. Significant differences between incidence of OFC among public health regions of Mississippi were examined using analysis of variance (P < 0.05). Cases were compared with historical data from 1980 to 1989. RESULTS: There were 184 patients who presented with OFC, with a statewide incidence of 0.83 per 1000 live births among 222,819 live births in the state across 6 years. The incidence of OFC was 0.83/1000 for Whites and 0.82/1000 for non-Whites versus a historical rate of 1.36 and 0.54, respectively. Significantly fewer children in the northern region (0.25/1000) were born with OFC than in central (1.21; P < 0.001) and southern (0.86; P < 0.001) regions. CONCLUSIONS: Results from this study suggest changing regional patterns of OFC in Mississippi. Although rates increased among non-White infants, the overall incidence of OFC has decreased compared with historical data. The findings may reflect actual incidence patterns in the state or the proximity of certain regions to Children's of Mississippi. Further study may reveal regional differences in risk factors underlying OFC incidence, and/or issues with access to cleft care for different regions in the state.

A portable thermal ablation device for cervical cancer prevention in a screen-and-treat setting: a randomized, noninferiority trial.

Implementing standard-of-care cryotherapy or electrosurgical excision to treat cervical precancers is challenging in resource-limited settings. An affordable technological alternative that is as effective as standard-of-care techniques would greatly improve access to treatment. This randomized controlled trial aims to demonstrate the noninferiority efficacy of a portable, battery-driven thermal ablation (TA) device compared to cryotherapy and electrosurgical excision (large loop excision of transformation zone (LLETZ)) to treat cervical precancer in a screen-and-treat program in Zambia. A total of 3,124 women positive on visual inspection with acetic acid and eligible for ablative therapy were randomized to one of the treatment arms. Human papillomavirus (HPV) testing was performed at baseline and at the follow-up. The primary outcome was treatment success, defined as either type-specific HPV clearance at the follow-up in participants positive for HPV at baseline, or a negative visual inspection with acetic acid test for those who had a negative HPV test at baseline. After a median follow-up of 12 months, treatment success rates were 74.0%, 71.1% and 71.4% for the TA, cryotherapy and LLETZ arms, respectively, thus demonstrating noninferiority (P = 0.83). TA was a safe and well-accepted procedure. Only 3.6% of those randomized to TA reported moderate-to-severe pain, compared to 6.5% and 1.9% for the cryotherapy and LLETZ arms, respectively. Thus, our randomized controlled trial demonstrates the safety and efficacy of TA, which is not inferior to cryotherapy or surgical excision.ClinicalTrials.gov registration: NCT02956239 .

Copy number variants underlie the major selective sweeps in insecticide resistance genes in Anopheles arabiensis from Tanzania.

To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. Knowledge of the mechanisms of resistance remains limited in Anopheles arabiensis, which in many parts of Africa is of increasing importance because it is apparently less susceptible to many indoor control interventions. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of resistance to pyrethroids. We performed a genome-wide association study to determine the molecular mechanisms of resistance to deltamethrin (commonly used in bednets) and PM, in An. arabiensis from two regions in Tanzania. Genomic regions of positive selection in these populations were largely driven by copy number variants (CNVs) in gene families involved in resistance to these two insecticides. We found evidence of a new gene cluster involved in resistance to PM, identifying a strong selective sweep tied to a CNV in the Coeae2g-Coeae6g cluster of carboxylesterase genes. Using complementary data from An. coluzzii in Ghana, we show that copy number at this locus is significantly associated with PM resistance. Similarly, for deltamethrin, resistance was strongly associated with a novel CNV allele in the Cyp6aa / Cyp6p cluster. Against this background of metabolic resistance, target site resistance was very rare or absent for both insecticides. Mutations in the pyrethroid target site Vgsc were at very low frequency in Tanzania, yet combining these samples with three An. arabiensis individuals from West Africa revealed a startling diversity of evolutionary origins of target site resistance, with up to 5 independent origins of Vgsc-995 mutations found within just 8 haplotypes. Thus, despite having been first recorded over 10 years ago, Vgsc resistance mutations in Tanzanian An. arabiensis have remained at stable low frequencies. Overall, our results provide a new copy number marker for monitoring resistance to PM in malaria mosquitoes, and reveal the complex picture of resistance patterns in An. arabiensis.

In Vitro Characterization and Rescue of VX Metabolism in Human Liver Microsomes.

Venomous agent X (VX) is an organophosphate acetylcholinesterase (AChE) inhibitor, and although it is one of the most toxic AChE inhibitors known, the extent of metabolism in humans is not currently well understood. The known metabolism in humans is limited to the metabolite identification from a single victim of the Osaka poisoning in 1994, which allowed for the identification of several metabolic products. VX has been reported to be metabolized in vitro by paraoxonase-1 and phosphotriesterase, although their binding constants are many orders of magnitude above the LD50, suggesting limited physiologic relevance. Using incubation with human liver microsomes (HLMs), we have now characterized the metabolism of VX and the formation of multiple metabolites as well as identified a Food and Drug Administration-approved drug [ethylenediaminetetraacetic acid (EDTA)] that enhances the metabolic rate. HLM incubation alone shows a pronounced increase in the metabolism of VX compared with buffer, suggesting that cytochrome P450-mediated metabolism of VX is occurring. We identified a biphasic decay with two distinct rates of metabolism. The enhancement of VX metabolism in multiple buffers was assessed to attempt to mitigate the effect of hydrolysis rates. The formation of VX metabolites was shown to be shifted with HLMs, suggesting a pathway enhancement over simple hydrolysis. Additionally, our investigation of hydrolysis rates in various common buffers used in biologic assays discovered dramatic differences in VX stability. The new human in vitro VX metabolic data reported points to a potential in vivo treatment strategy (EDTA) for rescue in individuals that are poisoned though enhancement of metabolism alongside existing treatments. SIGNIFICANCE STATEMENT: Venomous agent X (VX) is a potent acetylcholinesterase inhibitor and chemical weapon. To date, we do not possess a clear understanding of its metabolism in humans that would assist us in treating those exposed to it. This study now describes the human liver microsomal metabolism of VX and identifies ethylenediaminetetraacetic acid, which appears to enhance the rate of metabolism. This may provide a potential treatment option for human VX poisoning.

Parallel evolution in mosquito vectors - a duplicated esterase locus is associated with resistance to pirimiphos-methyl in An. gambiae.

The primary control methods for the African malaria mosquito, Anopheles gambiae, are based on insecticidal interventions. Emerging resistance to these compounds is therefore of major concern to malaria control programmes. The organophosphate, pirimiphos-methyl, is a relatively new chemical in the vector control armoury but is now widely used in indoor residual spray campaigns. Whilst generally effective, phenotypic resistance has developed in some areas in malaria vectors. Here, we used a population genomic approach to identify novel mechanisms of resistance to pirimiphos-methyl in Anopheles gambiae s.l mosquitoes. In multiple populations, we found large and repeated signals of selection at a locus containing a cluster of detoxification enzymes, some of whose orthologs are known to confer resistance to organophosphates in Culex pipiens. Close examination revealed a pair of alpha-esterases, Coeae1f and Coeae2f, and a complex and diverse pattern of haplotypes under selection in An. gambiae, An. coluzzii and An. arabiensis. As in Cx. pipiens, copy number variation seems to play a role in the evolution of insecticide resistance at this locus. We used diplotype clustering to examine whether these signals arise from parallel evolution or adaptive introgression. Using whole-genome sequenced phenotyped samples, we found that in West Africa, a copy number variant in Anopheles gambiae is associated with resistance to pirimiphos-methyl. Overall, we demonstrate a striking example of contemporary parallel evolution which has important implications for malaria control programmes.

The right banker plant for the right application: Comparison of three candidates for aphid biocontrol, barley (Hordeum vulgare L.), corn (Zea mays L.), and finger millet (Eleusine coracana (L.) Gaertn).

BACKGROUND: In temperate regions, aphid biological control in greenhouses is mostly achieved by the regular release of biocontrol agents. Due to the rapid growth rate of the aphid population, biocontrol agents must be released frequently in order to be present before pest outbreaks and to act rapidly to prevent exceeding the economic threshold. Banker plants reduce these numerous releases by providing natural enemies with a high-quality environment to develop and reproduce. Optimally, banker plants should be easy to produce, resistant to environmental conditions, provide a large amount of suitable banker prey in order to produce a high number of biocontrol agents, and resist the herbivory pressure of the banker prey. The present study aimed to compare the value of three banker plant candidates of the Poaceae family under laboratory and greenhouse conditions: barley (Hordeum vulgare L.), finger millet (Eleusine coracana (L.) Gaertn), and corn (Zea mays L.). RESULTS: Our results show that the three plants were suitable for different contexts. Finger millet yielded the biggest fresh plant biomass, supported the highest load of banker prey, and resisted aphid feeding longer than the other plant species. Corn was the cheapest to produce, and barley was the fastest to grow. CONCLUSIONS: Overall, finger millet could be more fitted for long crop cycles, pests with rapid population growth rates, and voracious or fast-reproducing biocontrol agents. Meanwhile, barley and corn may be better suited for rapid crop cycles, pests with slow population growth rates, and biocontrol agents that are not too voracious or have low reproductive rates. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Larval development and voracity of Eupeodes americanus (Diptera: Syrphidae): comparison of the focal prey Aphis gossypii (Hemiptera: Aphididae) and the banker prey Rhopalosiphum padi (Hemiptera: Aphididae).

Unlike European species, the potential of Nearctic syrphids as biological control agents is still poorly studied. However, the American hoverfly, Eupeodes americanus (Wiedemann), has recently demonstrated promising traits as a biocontrol agent, notably against the foxglove aphid, Aulacorthum solani Kaltenbach, on pepper. The present study aims to extend our knowledge of the American hoverfly by evaluating its potential as a biocontrol agent in a banker plant system against the melon aphid, Aphis gossypii Glover, in a greenhouse cucumber crop. The preimaginal development and voracity of E. americanus were compared when preying upon the focal prey/pest (A. gossypii) or the banker prey (bird cherry-oat aphid, Rhopalosiphum padi L.) by daily observations of larvae from egg to adult. Preimaginal development time, survival rate, and occurrence of deformation were similar on both prey species. The weight of third instar and pupae, however, was higher for larvae that fed on the banker prey. The ad libitum voracity of the syrphid larvae was generally very high and did not significantly differ between prey species, except for the third-instar larvae which consumed more focal prey. Results suggest that a banker plant system involving the bird cherry-oat aphid may be a promising tactic for utilizing E. americanus for melon aphid biocontrol.

Mechanisms of transcriptional regulation in Anopheles gambiae revealed by allele specific expression.

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in cis, by regulatory sequences on the same chromosome, and by trans acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in cis-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb resistant and susceptible Anopheles gambiae strains to identify cis-regulated genes that might be responsible for the resistant phenotype using RNAseq, and cis-regulatory module sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele specific expression in hybrids of insecticide susceptible and resistant strains, suggesting cis regulation is an important mechanism of gene expression regulation in Anopheles gambiae. The genes showing allele specific expression included a higher proportion of Anopheles specific genes on average younger than genes those with balanced allelic expression.

Impact of age at vaccination and cervical HPV infection status on binding and neutralizing antibody titers at 10 years after receiving single or higher doses of quadrivalent HPV vaccine.

Long-term follow-up of a cohort of unmarried girls who received one, two, or three doses of quadrivalent HPV vaccine, between 10 and 18 years of age, in an Indian multi-centric study allowed us to compare antibody responses between the younger and older age cohorts at 10-years post-vaccination, and study the impact of initiation of sexual activity and cervical HPV infections on antibody levels. Among the younger (10-14 years) recipients of a single dose, 97.7% and 98.2% had detectable binding antibody titers against HPV 16 and HPV 18 respectively at ten years post-vaccination. The proportions among those receiving a single dose at age 15-18 years were 92.3% and 94.2% against HPV 16 and HPV 18 respectively. Mean HPV 16 binding antibody titers were 2.1 folds (95%CI 1.4 to 3.3) higher in those vaccinated at ages 10-14 years, and 1.9 folds (95%CI 1.2 to 3.0) higher in those vaccinated at 15-18 years compared to mean titers seen in the unvaccinated women. Compared to previous timepoints of 36 or 48 months, binding antibodies against HPV 16 and neutralizing antibodies against both HPV 16 and HPV 18 were significantly higher at 10 years. This rise was more pronounced in participants vaccinated at 15-18 years. No association of marital status or cervical HPV infections was observed with the rise in titer. Durability of antibody response in single dose recipients correlated well with the high efficacy of a single dose against persistent HPV 16/18 infections irrespective of age at vaccination, as we reported earlier.

Health and economic effects of introducing single-dose or two-dose human papillomavirus vaccination in India.

BACKGROUND: Cervical cancer is a major public health problem in India, where access to prevention programmes is low. The WHO-Strategic Advisory Group of Experts recently updated their recommendation for human papillomavirus (HPV) vaccination to include a single-dose option in addition to the two-dose option, which could make HPV vaccination programmes easier to implement and more affordable. METHODS: We combined projections from a type-specific HPV transmission model and a cancer progression model to assess the health and economic effects of HPV vaccination at national and state level in India. The models used national and state-specific Indian demographic, epidemiological and cost data, and single-dose vaccine efficacy and immunogenicity data from the International Agency for Research on Cancer India vaccine trial with 10-year follow-up. We compared single-dose and two-dose HPV vaccination for a range of plausible scenarios regarding single-dose vaccine protection, coverage and catch-up. We used a healthcare sector payer perspective with a time horizon of 100 years. RESULTS: Under the base-case scenario of lifelong protection of single-dose vaccination in 10-year-old girls with 90% coverage, the discounted incremental cost-effectiveness ratio (ICER) of nationwide vaccination relative to no vaccination was US$406 (₹INR30 000) per DALY (disability-adjusted life-years) averted. This lay below an opportunity-cost-based threshold of 30% Indian gross domestic product per capita in each Indian state (state-specific ICER range: US$67-US$593 per DALY averted). The ICER of two-dose vaccination versus no vaccination vaccination was US$1404 (₹INR104 000). The ICER of two-dose vaccination versus single-dose vaccination, assuming lower initial efficacy and waning of single-dose vaccination, was at least US$2282 (₹INR169 000) per DALY averted. CONCLUSIONS: Nationwide introduction of single-dose HPV vaccination at age 10 in India is highly likely to be cost-effective whereas extending the number of doses from one to two would have a less favourable profile.

Assessment of organization of cervical and breast cancer screening programmes in the Latin American and the Caribbean states: The CanScreen5 framework.

BACKGROUND: In the Community of Latin American and Caribbean States (CELAC), breast cancer and cervical cancer are the first and third causes of cancer death among females. The objectives are to assess the characteristics of the cervical and breast cancer screening programmes in CELAC, their level of organization, and the association of screening organization and coverage of essential health services. METHODS: Representatives of the Ministries of Health of 33 countries were invited to the CanScreen5 project. Twenty-seven countries participated in a "Train The Trainers" programme on cancer screening, and 26 submitted data using standardized questionnaires. Data were discussed and validated. The level of organization of the screening programmes was examined adapting the list of essential elements of organized screening programmes identified in a recently published IARC study. RESULTS: Twenty-one countries reported a screening programme for cervical cancer and 15 for breast cancer. For cervical cancer, 14 countries dedicated budget for screening (66.7%), and women had to pay in 3 countries for screening (14.3%), 9 for diagnosis (42.9%) and 8 for treatment (38.1%). Only 4 countries had a system to invite women individually (19.0%). For breast cancer, 8 countries dedicated budget for screening (53.3%), and women had to pay for screening in 3 countries (20.0%), diagnosis in 7 (46.7%) and treatment in 6 (40.0%). One country (6.7%) invited women individually. There was variability in the level of organization of both cancer screening programmes. The level of organization of cervical cancer screening and coverage of essential health services were correlated. CONCLUSION: Large gaps were identified in the organization of cervical and breast cancer screening services. CELAC governments need pragmatic public health policies and strengthened health systems. They should guarantee sustainable funding, and universal access to cancer diagnosis and treatment. Moreover, countries should enhance their health information system and ensure adequate monitoring and evaluation.

Genome-wide association studies reveal novel loci associated with pyrethroid and organophosphate resistance in Anopheles gambiae and Anopheles coluzzii.

Resistance to insecticides in Anopheles mosquitoes threatens the effectiveness of malaria control, but the genetics of resistance are only partially understood. We performed a large scale multi-country genome-wide association study of resistance to two widely used insecticides: deltamethrin and pirimiphos-methyl, using sequencing data from An. gambiae and An. coluzzii from ten locations in West Africa. Resistance was highly multi-genic, multi-allelic and variable between populations. While the strongest and most consistent association with deltamethrin resistance came from Cyp6aa1, this was based on several independent copy number variants (CNVs) in An. coluzzii, and on a non-CNV haplotype in An. gambiae. For pirimiphos-methyl, signals included Ace1, cytochrome P450s, glutathione S-transferases and the nAChR target site of neonicotinoid insecticides. The regions around Cyp9k1 and the Tep family of immune genes showed evidence of cross-resistance to both insecticides. These locally-varying, multi-allelic patterns highlight the challenges involved in genomic monitoring of resistance, and may form the basis for improved surveillance methods.

Colorectal Cancer Screening Pilot Project in Tehran-Iran, a Feasibility Study.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in Iran, where there is no organised CRC-screening programme. This study aimed to evaluate feasibility of CRC screening using a qualitative fecal immunochemical test (FIT) among Iranian average-risk adults. METHODS: In this feasibility study, 7039 individuals aged 50-75 years were invited by community health workers (CHWs) in southern Tehran and its suburban districts between April 2018 and November 2019. The CHWs performed a qualitative FIT with cut-off level 50 ng Hb/mL buffer and referred those with positive-FIT for colonoscopy to the endoscopy center of Shariati hospital in Tehran. Outcomes included acceptance rate, FIT positivity rate, colonoscopy compliance, detection rates and positive predictive values (PPVs) with 95% confidence interval for CRC and advanced adenomas (AAs). RESULTS: Acceptance rate at initial invitation was 71.7%. From 4974 average-risk adults (1600 males and 3374 females) who were offered FIT, 96.8% (n=4813) provided valid samples, of whom 471 (9.8%) tested positive. Among FIT-positive participants, 150 (31.8%) underwent colonoscopy; CRC was detected in 2.0% (n=3) and adenomas in 27.3% (n=41). Detection rate of CRC and AAs per 1000-FIT-screened participants was 0.6 (0.1-1.8) [males: 0.7 (0.01-3.6), females: 0.6 (0.07-2.0)] and 4.2 (2.5-6.4) [males: 5.9 (2.6-11.0), females: 3.4 (1.7-6.0)], respectively. PPVs were 2.0% (0.4-5.7) for CRC and 13.3% (8.3-19.8) for AAs. There was no association between gender and the studied outcomes. CONCLUSION: Our results partially support the feasibility of scaling up organized CRC-screening through the existing healthcare system in Iran; it remains to be discussed carefully to ensure the capacity of healthcare system for adequate colonoscopy services.

LLIN Evaluation in Uganda Project (LLINEUP) - Plasmodium infection prevalence and genotypic markers of insecticide resistance in Anopheles vectors from 48 districts of Uganda.

Background: In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus the synergist piperonyl butoxide (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, cross-sectional entomological surveys were carried out at baseline and then every 6 months for two years. In each survey, ten households per HSD were randomly selected for indoor household entomological collections. Results: Overall, 5395 female Anopheles mosquitoes were collected from 5046 households. The proportion of mosquitoes infected with Plasmodium falciparum did not change significantly over time, while infection with non-falciparum malaria decreased in An. gambiae s.s, but not An. funestus. The frequency of genetic markers associated with pyrethroid resistance increased significantly over time, but the rate of change was not different between the two LLIN types. The knock-down resistance (kdr) mutation Vgsc-995S declined over time as Vgsc-995F, the alternative resistance mutation at this codon, increased. Vgsc-995F appears to be spreading into Uganda. Conclusions: Distribution of LLINs in Uganda was associated with reductions in parasite prevalence and vector density, but the proportion of infective mosquitoes remained stable, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors and highlights the potential benefits of resistance management strategies.Trial registration:: This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395.

Trophic Interactions of Ceutorhynchinae spp. (Coleoptera: Curculionidae) with Their Host Plants (Brassicaceae) and Their Parasitoids in the Agroecosystem of Quebec, Canada.

The genus Ceutorhynchus Germar (Coleoptera: Curculionidae) is composed of canola pests, natural enemies of Brassicaceae, and other species associated with non-crop and non-weed plants. This study aimed to establish trophic associations of Ceutorhynchus with their host plants and with their parasitoids in the agricultural landscape, in order to assess the actual beneficial or noxious ecological roles of the insects. Trophic associations were established by identifying Ceutorhynchus species and their parasitoids emerging from collected Brassicaceae plants in areas adjacent to canola fields and other crops in 2019 and 2020. Five Ceutorhynchus species were collected and identified as hosts of parasitoids in the families Pteromalidae and Eulophidae. Two functional groups were characterized: natural enemies of weeds and agricultural pests. The exotic wormseed wallflower, Erysimum cheiranthoides was identified as a new host plant of the invasive canola pest Ceutorhynchus obstrictus (Marsham), and the native tower rockcress, Arabis glabra, as a new host plant of the native Ceutorhynchus neglectus Blatchley. Association between the exotic Ceutorhynchus typhae (Herbst) and a parasitoid of the genus Elachertodomyia is reported for the first time. Finally, Ceutorhynchus neglectus and C. typhae hosted the exotic parasitoid Trichomalus perfectus, an important natural enemy of C. obstrictus.

Detection of the Synthetic Coolant Menthone 1,2-Glycerol Ketal in an e-Liquid and in Electronic Waterpipe Aerosols Therefrom.

The presence and toxicological risks of synthetic coolants in electronic nicotine delivery systems (ENDS) have not been thoroughly studied. We identified the synthetic coolant menthone 1,2-glycerol ketal (MGK) in a menthol-flavored e-liquid at a concentration of ∼170 µg/mL. We also detected MGK in aerosols resulting from heating the e-liquid with an electronic waterpipe. MGK was initially detected in the e-liquid by two-dimensional gas chromatography-time-of-flight mass spectrometry. To avoid potential analytical artifacts that could result from heating samples in the injection port of the gas chromatograph, quantitation of MGK in the e-liquid was accomplished using a liquid chromatography-tandem mass spectrometry method. Following recent reports identifying other synthetic coolants in e-liquids, these results add knowledge about inhalation exposures from ENDS use and suggest the importance of future research to study the potential inhalation toxicity related to the use of MGK-containing e-liquids in ENDS devices. Furthermore, the results demonstrate the ability to quantify ketals in e-liquids using liquid chromatography methods.