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Objectives: To determine the associated pathogen during the 2023 conjunctivitis outbreak in Vietnam Methods: RNA-sequencing was used to identify pathogens before and during the outbreak. Results: 24 patients with infectious conjunctivitis between March and October 2023 from Hai Yen Vision Institute in Vietnam were swabbed. Coxsackievirus A24v was the most common pathogen identified. Phylogenetic analysis of these strains demonstrates similarities to the Coxsackievirus identified in the 2022 India outbreak. Human adenovirus D was also circulating. Ocular findings of tearing, purulence, and itching were common in this outbreak. Conclusions: Multiple viruses can co-circulate during conjunctivitis outbreaks. Hemorrhagic conjunctivitis, commonly associated with coxsackievirus conjunctivitis, was not a common clinical sign in this outbreak. Repeat genetic surveillance, with the notable inclusion of RNA virus detection strategies, is important for outbreak detection.

Abstract Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1–9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0–54%) and seroconversion rates (range: 0–15 per 100 person-years) correlate with PCR prevalence (r: 0.87, 95% CI: 0.57, 0.97). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any PCR-identified infection at high sensitivity ( >90%) and moderate specificity (69–75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination.

PurposeTo assess the differences in the measurement of central foveal thickness (CFT) in patients with macular edema (ME) between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT).DesignThis is a retrospective, cross-sectional study.MethodsGroup A consisted of participants with well-horizontal OCT B-scan images and group B consisted of participants with tilted OCT B-scan. We manually measured the CFT under the two display modes, and the values were compared statistically using the paired t-test. Spearman’s test was used to assess the correlations between the OCT image tilting angle (OCT ITA) and the differences in CFT measurement. The area under the curve (AUC) was calculated to define the OCT ITA cutoff for a defined CFT difference.ResultsIn group A, the mean CFT in the 1:1 pixel display mode was 420.21 ± 130.61 µm, similar to the mean CFT of 415.27 ± 129.85 µm in the 1:1 micron display mode. In group B, the median CFT in the 1:1 pixel display mode is 409.00 μm (IQR: 171.75 μm) and 368.00 μm (IQR: 149.00 μm) in the 1:1 micron display mode. There were significant differences between the two display modes with the median (IQR) absolute difference and median (IQR) relative difference of 38.00 μm (75.00 μm) and 10.19% (21.91%) (all p = 0.01). The differences in CFT measurement between the two display modes were correlated with the OCT ITA (absolute differences, r = 0.88, p < 0.01; relative differences, r = 0.87, p < 0.01). The AUC for a predefined CFT difference was 0.878 (10 μm), 0.933 (20 μm), 0.938 (30 μm), 0.961 (40 μm), 0.962 (50 μm), and 0.970 (60 μm).ConclusionIn patients with DM, when the OCT B-scan images were well-horizontal, manual CFT measurements under the two display modes were similar, but when the B-scan images were tilted, the CFT measurements were different under the two display modes, and the differences were correlated to the OCT ITA.

Purpose: Description of safety and efficacy of micropulse Transscleral cyclophotocoagulation as a treatment option for refractory glaucoma. Methods: This is a prospective study including 39 eyes of 31 patients followed for refractory glaucoma, who benefited from transscleral cyclophotocoagulation using a microplused laser. The main indication for the procedure was increased ocular pressure refractory to quadritherapy in various types of glaucoma. The patients were treated using iridex Cyclo G6 laser with a Micropulse P3 infrared probe with a wavelength of 810 ​nm. The parameters for the procedure were a duration of 90 ​s per hemisphere with a power of 2000 mW and an energy of 180 ​J. Both the upper and lower hemispheres were treated in the same procedure, sparing the 3 o'clock and 9 o'clock meridians, and all the patients benefited from a single treatment session. The following parameters were evaluated: ocular pain and overall tolerance; visual acuity; and the evolution of IOP postoperatively up to 9 months. Results: The glaucoma subtypes treated are as follows: primary open-angle glaucoma (n ​= ​05), chronic angle-closure glaucoma (n ​= ​13), neovascular glaucoma (n ​= ​07), aphakic glaucoma (n ​= ​06), malignant glaucoma (n ​= ​04), post-traumatic angle recession (n ​= ​02), and inflammatory glaucoma (n ​= ​02). The mean pre-operative intraocular pressure was 42.3 ​± ​5.2 ​mmHg and the mean post-operative intraocular pressure at 9 months was 16.9 ​± ​1.9 ​mmHg. The reduction in IOP was 49.9%. The average number of intraocular pressure-lowering medications used prior to surgery was four, and the average number of medications used at the 9-month post-operative visit was 2.0 ​± ​1.2 (70.3% of patients were on dual therapy). The overall success rate was 60.5%. Conclusions: Micropulse transscleral cyclophotocoagulation appears to be a safe and efficient treatment for refractory glaucoma. Its indications should therefore be broadened and proposed early in various situations.

BackgroundTrachoma is the leading infectious cause of blindness. To reduce transmission, water, sanitation, and hygiene (WaSH) improvements are promoted through a comprehensive public health strategy. Evidence supporting the role of WaSH in trachoma elimination is mixed and it remains unknown what WaSH coverages are needed to effectively reduce transmission.Methods/findingsWe used g-computation to estimate the impact on the prevalence of trachomatous inflammation-follicular among children aged 1-9 years (TF1-9) when hypothetical WaSH interventions raised the minimum coverages from 5% to 100% for "nearby" face-washing water (ConclusionsOur results support Sustainable Development Goal 6 and provide insight into potential WaSH-related coverage targets for trachoma elimination. Targets can be tested in future trials to improve evidence-based WaSH guidance for trachoma.

Recent evidence indicates mass azithromycin distribution reduces under-5 mortality. This intervention is being considered for child survival programs in high mortality sub-Saharan African settings. The delivery approach used in prior studies required a full-time census and distribution team, which is not feasible for most programs. To determine the optimal programmatic approach to delivery, this study aimed to compare treatment coverage, costs, and acceptability of different delivery approaches with existing community health workers (CHWs). This cluster-randomized trial included rural and peri-urban communities in Dosso, Niger (clinicaltrials.gov, NCT04774991). A random sample of 80 eligible communities was randomized 1:1 to biannual door-to-door or fixed-point delivery of oral azithromycin to children 1-59 months old over 1 year. Data analysts alone were masked given the nature of the intervention. The primary outcome was community-level treatment coverage defined as the number of children treated recorded by CHWs divided by the number of eligible children determined using a post-distribution census. Costs were monitored through routine administrative data collection and micro-costing. The census included survey questions on intervention acceptability among caregivers, community leaders, and CHWs. After randomization, 1 community was excluded due to inaccuracies in available administrative data, resulting in 39 communities receiving door-to-door delivery. At the second distribution, community-level mean treatment coverage was 105% (SD 44%) in the door-to-door arm and 92% (SD 20%) in the fixed-point arm (Mean difference 13%, 95% CI -2% to 28%, P-value = 0.08). The total cost per dose delivered was $1.91 in the door-to-door arm and $2.51 in the fixed-point arm. Indicators of acceptability were similar across stakeholder groups in both arms, with most respondents in each group indicating a preference for door-to-door. Overall, door-to-door delivery is the preferred approach to azithromycin distribution in this setting and might reach more children at a lower cost per dose delivered than fixed-point. Trial Registration: clinicaltrials.gov NCT04774991.

Abstract Background Biannual distribution of azithromycin to children 1–59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1–11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance. Methods AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1–11: biannual azithromycin to children 1–11 months old with placebo to children 12–59 months old, 2) azithromycin 1–59: biannual azithromycin to children 1–59 months old, or 3) placebo: biannual placebo to children 1–59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1–59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1–59 months old comparing the azithromycin 1–59 and placebo arms, 2) children 1–11 months old comparing the azithromycin 1–11 and placebo arm, and 3) children 12–59 months in the azithromycin 1–11 and azithromycin 1–59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1–59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1–59 months old. Discussion As high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival. Trial registration This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987 ).

Abstract Background The World Health Organization (WHO) recommends annual mass azithromycin distribution until districts drop below 5% prevalence of trachomatous inflammation—follicular (TF). Districts with very low TF prevalence may have little or no transmission of the ocular strains of Chlamydia trachomatis that cause trachoma, and additional rounds of mass azithromycin distribution may not be useful. Here, we describe the protocol for a randomized controlled trial designed to evaluate whether mass azithromycin distribution can be stopped prior to the current WHO guidelines. Methods The Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) study is a 1:1 community randomized non-inferiority trial designed to evaluate whether mass azithromycin distribution can be stopped in districts with baseline prevalence of TF under 20%. Communities in Maradi, Niger are randomized after baseline assessment either to continued annual mass azithromycin distribution or stopping annual azithromycin distribution over a 3-year period. We will compare the prevalence of ocular C. trachomatis (primary outcome), TF and other clinical signs of trachoma, and serologic markers of trachoma after 3 years. We hypothesize that stopping annual azithromycin distribution will be non-inferior to continued annual azithromycin distributions for all markers of trachoma prevalence and transmission. Discussion The results of this trial are anticipated to provide potentially guideline-changing evidence for when mass azithromycin distributions can be stopped in low TF prevalence areas. Trial registration number This study is registered at clinicaltrials.gov ( NCT04185402 ). Registered December 4, 2019; prospectively registered pre-results.

Abstract Background Biannual mass azithromycin administration to preschool children reduces all-cause mortality, but the mechanism for the effect is not understood. Azithromycin has activity against malaria parasites, and malaria is a leading cause of child mortality in the Sahel. The effect of biannual versus annual azithromycin distribution for trachoma control on serological response to merozoite surface protein 1 (MSP-119), a surrogate for malaria incidence, was evaluated among children in Niger. Methods Markers of malaria exposure were measured in two arms of a factorial randomized controlled trial designed to evaluate targeted biannual azithromycin distribution to children under 12 years of age compared to annual azithromycin to the entire community for trachoma control (N = 12 communities per arm). Communities were treated for 36 months (6 versus 3 distributions). Dried blood spots were collected at 36 months among children ages 1–5 years, and MSP-119 antibody levels were assessed using a bead-based multiplex assay to measure malaria seroprevalence. Results Antibody results were available for 991 children. MSP-119 seropositivity was 62.7% in the biannual distribution arm compared to 68.7% in the annual arm (prevalence ratio 0.91, 95% CI 0.83 to 1.00). Mean semi-quantitative antibody levels were lower in the biannual distribution arm compared to the annual arm (mean difference − 0.39, 95% CI − 0.05 to − 0.72). Conclusions Targeted biannual azithromycin distribution was associated with lower malaria seroprevalence compared to that in a population that received annual distribution. Trial Registration Clinicaltrials.gov NCT00792922

The World Health Organization (WHO) recommends continuing azithromycin mass drug administration (MDA) for trachoma until endemic regions drop below 5% prevalence of active trachoma in children aged 1-9 years. Azithromycin targets the ocular strains of Chlamydia trachomatis that cause trachoma. Regions with low prevalence of active trachoma may have little if any ocular chlamydia, and, thus, may not benefit from azithromycin treatment. Understanding what happens to active trachoma and ocular chlamydia prevalence after stopping azithromycin MDA may improve future treatment decisions. We systematically reviewed published evidence for community prevalence of both active trachoma and ocular chlamydia after cessation of azithromycin distribution. We searched electronic databases for all peer-reviewed studies published before May 2020 that included at least 2 post-MDA surveillance surveys of ocular chlamydia and/or the active trachoma marker, trachomatous inflammation-follicular (TF) prevalence. We assessed trends in the prevalence of both indicators over time after stopping azithromycin MDA. Of 140 identified studies, 21 met inclusion criteria and were used for qualitative synthesis. Post-MDA, we found a gradual increase in ocular chlamydia infection prevalence over time, while TF prevalence generally gradually declined. Ocular chlamydia infection may be a better measurement tool compared to TF for detecting trachoma recrudescence in communities after stopping azithromycin MDA. These findings may guide future trachoma treatment and surveillance efforts.

Au Niger, les aires protégées perdent chaque année plusieurs hectares de leurs étendues sous les effets conjugués de la pression anthropique et des changements climatiques. Pour appréhender cette dégradation continue du couvert végétal, une étude a été menée dans la forêt protégée de Baban Rafi. Cette étude a pour objectif principal de mettre en évidence la dynamique spatio-temporelle des formations forestières entre 1996 et 2016 au moyen de la télédétection et des Systèmes d’information géographique (SIG). Pour ce faire, une exploitation des images satellitaires de type Landsat LT05 de l’année 1996, Landsat LE07 de l’année 2005 et Sentinelle T32PKV pour l’année 2016 couplée avec la vérité terrain à l’aide du GPS dont 17 points visités a été faite. Ceci a permis d’identifier 8 types d’occupation des terres que sont le cordon ripicole, la savane arborée, la savane arbustive, les cultures pluviales, la jachère, la zone habitée, les sols nus et le ravin. Les résultats cartographiques révèlent également une régression de la couverture forestière de l’ordre de 171,79 ha/an entre 1996 et 2016. Cette régression s’est faite au profit des zones de culture qui ont augmenté de 3 450 ha. Ces résultats suggèrent la mise en place d’une stratégie efficace de gestion durable de la forêt protégée de Baban Rafi pour éviter sa disparition à long terme. Mots clés: Dégradation, télédétection, dynamique, gestion durable, Forêt protégée de Baban Rafi, Niger

Objective To evaluate the effectiveness and safety of azithromycin 1.5% eye drops under field conditions to reduce active trachoma in a highly endemic district in Cameroon. This is a follow-up of an initial report published in 2010.Methods and analysis Three annual campaigns were performed in 2008, 2009 and 2010 to treat the population (~1 20 000 individuals) of the Kolofata Health District with topical azithromycin 1.5% (one drop in each eye, morning and evening for three consecutive days). The effectiveness of this intervention against active trachoma was assessed in children aged 1–9 years in cross-sectional studies prior to each mass treatment using a systematic sampling procedure (in 2008, 2009 and 2010) and then 1 year (2011) and 3 years (2013) after the last intervention among the villages with previously high active trachoma prevalence or never tested.Results The prevalence of trachomatous inflammation—follicular (TF) dropped from 24.0% (95% CI 20.7 to 27.5) before treatment to 2.8% (95% CI 2.2 to 3.7) 1 year after completion of the 3 year campaign. Trachomatous inflammation—intense was present in only 4 (0.2%) children 1 year after the third round of treatment. Three years after the last campaign, the surveillance survey among the most prevalent villages and villages never tested before showed a prevalence of 5.2% (95% CI 3.6 to 7.2) of active trachoma. Tolerance was excellent, with no report of treatment interruption, serious ocular or systemic adverse events.Conclusion Annual mass treatment with azithromycin eye drops was shown to be effective in reducing TF to a level ≤5% one year after a 3-round annual mass treatment in an endemic region at the district level.

BACKGROUND/AIMS:Trachoma programs base treatment decisions on the community prevalence of the clinical signs of trachoma, assessed by direct examination of the conjunctiva. Automated assessment could be more standardized and more cost-effective. We tested the hypothesis that an automated algorithm could classify eyelid photographs better than chance. METHODS:A total of 1,656 field-collected conjunctival images were obtained from clinical trial participants in Niger and Ethiopia. Images were scored for trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI) according to the simplified World Health Organization grading system by expert raters. We developed an automated procedure for image enhancement followed by application of a convolutional neural net classifier for TF and separately for TI. One hundred images were selected for testing TF and TI, and these images were not used for training. RESULTS:The agreement score for TF and TI tasks for the automated algorithm relative to expert graders was κ = 0.44 (95% CI: 0.26 to 0.62, P < 0.001) and κ = 0.69 (95% CI: 0.55 to 0.84, P < 0.001), respectively. DISCUSSION:For assessing the clinical signs of trachoma, a convolutional neural net performed well above chance when tested against expert consensus. Further improvements in specificity may render this method suitable for field use.

BACKGROUND:Program decision-making for trachoma elimination currently relies on conjunctival clinical signs. Antibody tests may provide additional information on the epidemiology of trachoma, particularly in regions where it is disappearing or elimination targets have been met. METHODS:A cluster-randomized trial of mass azithromycin distribution strategies for trachoma elimination was conducted over three years in a mesoendemic region of Niger. Dried blood spots were collected from a random sample of children aged 1-5 years in each of 24 study communities at 36 months after initiation of the intervention. A multiplex bead assay was used to test for antibodies to two Chlamydia trachomatis antigens, Pgp3 and CT694. We compared seropositivity to either antigen to clinical signs of active trachoma (trachomatous inflammation-follicular [TF] and trachomatous inflammation-intense [TI]) at the individual and cluster level, and to ocular chlamydia prevalence at the community level. RESULTS:Of 988 children with antibody data, TF prevalence was 7.8% (95% CI 6.1 to 9.5) and TI prevalence was 1.6% (95% CI 0.9 to 2.6). The overall prevalence of antibody positivity to Pgp3 was 27.2% (95% CI 24.5 to 30), and to CT694 was 23.7% (95% CI 21 to 26.2). Ocular chlamydia infection prevalence was 5.2% (95% CI 2.8 to 7.6). Seropositivity to Pgp3 and/or CT694 was significantly associated with TF at the individual and community level and with ocular chlamydia infection and TI at the community level. Older children were more likely to be seropositive than younger children. CONCLUSION:Seropositivity to Pgp3 and CT694 correlates with clinical signs and ocular chlamydia infection in a mesoendemic region of Niger. TRIAL REGISTRATION:ClinicalTrials.gov NCT00792922.

Abstract Background The World Health Organization aims to control blinding trachoma by 2020. Decisions on whether to start and stop mass treatments and when to declare that control has been achieved are currently based on clinical examination data generated in population-based surveys. Thresholds are based on the district-level prevalence of trachomatous inflammation–follicular (TF) in children aged 1–9 years. Forecasts of which districts may and may not meet TF control goals by the 2020 target date could affect resource allocation in the next few years. Methods We constructed a hidden Markov model fit to the prevalence of two clinical signs of trachoma and PCR data in 24 communities from the recent PRET-Niger trial. The prevalence of TF in children in each community at 36 months was forecast given data from earlier time points. Forecasts were scored by the likelihood of the observed results. We assessed whether use of TF with additional TI and PCR data rather than just the use of TF alone improves forecasts, and separately whether incorporating a delay in TF recovery is beneficial. Results Including TI and PCR data did not significantly improve forecasts of TF. Forecasts of TF prevalence at 36 months by the model with the delay in TF recovery were significantly better than forecasts by the model without the delay in TF recovery (p = 0.003). A zero-inflated truncated normal observation model was better than a truncated normal observation model, and better than a sensitivity-specificity observation model. Conclusion The results in this study suggest that future studies could consider using just TF data for forecasting, and should include a delay in TF recovery. Trial registration Clinicaltrials.gov NCT00792922

BACKGROUND:Trachoma programs rely on guidelines made in large part using expert opinion of what will happen with and without intervention. Large community-randomized trials offer an opportunity to actually compare forecasting methods in a masked fashion. METHODS:The Program for the Rapid Elimination of Trachoma trials estimated longitudinal prevalence of ocular chlamydial infection from 24 communities treated annually with mass azithromycin. Given antibiotic coverage and biannual assessments from baseline through 30 months, forecasts of the prevalence of infection in each of the 24 communities at 36 months were made by three methods: the sum of 15 experts' opinion, statistical regression of the square-root-transformed prevalence, and a stochastic hidden Markov model of infection transmission (Susceptible-Infectious-Susceptible, or SIS model). All forecasters were masked to the 36-month results and to the other forecasts. Forecasts of the 24 communities were scored by the likelihood of the observed results and compared using Wilcoxon's signed-rank statistic. FINDINGS:Regression and SIS hidden Markov models had significantly better likelihood than community expert opinion (p = 0.004 and p = 0.01, respectively). All forecasts scored better when perturbed to decrease Fisher's information. Each individual expert's forecast was poorer than the sum of experts. INTERPRETATION:Regression and SIS models performed significantly better than expert opinion, although all forecasts were overly confident. Further model refinements may score better, although would need to be tested and compared in new masked studies. Construction of guidelines that rely on forecasting future prevalence could consider use of mathematical and statistical models. TRIAL REGISTRATION:Clinicaltrials.gov NCT00792922.

Antibiotic use on animals demonstrates improved growth regardless of whether or not there is clinical evidence of infectious disease. Antibiotics used for trachoma control may play an unintended benefit of improving child growth.In this sub-study of a larger randomized controlled trial, we assess anthropometry of pre-school children in a community-randomized trial of mass oral azithromycin distributions for trachoma in Niger. We measured height, weight, and mid-upper arm circumference (MUAC) in 12 communities randomized to receive annual mass azithromycin treatment of everyone versus 12 communities randomized to receive biannual mass azithromycin treatments for children, 3 years after the initial mass treatment. We collected measurements in 1,034 children aged 6-60 months of age.We found no difference in the prevalence of wasting among children in the 12 annually treated communities that received three mass azithromycin distributions compared to the 12 biannually treated communities that received six mass azithromycin distributions (odds ratio = 0.88, 95% confidence interval = 0.53 to 1.49).We were unable to demonstrate a statistically significant difference in stunting, underweight, and low MUAC of pre-school children in communities randomized to annual mass azithromycin treatment or biannual mass azithromycin treatment. The role of antibiotics on child growth and nutrition remains unclear, but larger studies and longitudinal trials may help determine any association.

Clinical examination of trachoma is used to justify intervention in trachoma-endemic regions. Currently, field graders are certified by determining their concordance with experienced graders using the kappa statistic. Unfortunately, trachoma grading can be highly variable and there are cases where even expert graders disagree (borderline/marginal cases). Prior work has shown that inclusion of borderline cases tends to reduce apparent agreement, as measured by kappa. Here, we confirm those results and assess performance of trainees on these borderline cases by calculating their reliability error, a measure derived from the decomposition of the Brier score.We trained 18 field graders using 200 conjunctival photographs from a community-randomized trial in Niger and assessed inter-grader agreement using kappa as well as reliability error. Three experienced graders scored each case for the presence or absence of trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI). A consensus grade for each case was defined as the one given by a majority of experienced graders. We classified cases into a unanimous subset if all 3 experienced graders gave the same grade. For both TF and TI grades, the mean kappa for trainees was higher on the unanimous subset; inclusion of borderline cases reduced apparent agreement by 15.7% for TF and 12.4% for TI. When we assessed the breakdown of the reliability error, we found that our trainees tended to over-call TF grades and under-call TI grades, especially in borderline cases.The kappa statistic is widely used for certifying trachoma field graders. Exclusion of borderline cases, which even experienced graders disagree on, increases apparent agreement with the kappa statistic. Graders may agree less when exposed to the full spectrum of disease. Reliability error allows for the assessment of these borderline cases and can be used to refine an individual trainee's grading.

Control programs for trachoma use mass antibiotic distributions to treat ocular Chlamydia trachomatis in an effort to eliminate this disease worldwide. To determine whether children infected with ocular Chlamydia are more likely to present later for examination than those who are uninfected, we compare the order of presentation for examination of children 0-5 years, and the presence of ocular Chlamydia by PCR in 4 villages in Niger where trachoma is endemic.We conducted a cluster-randomized, controlled trial where 48 randomly selected villages in Niger are divided into 4 study arms of different mass treatment strategies. In a substudy of the main trial, we randomly selected 1 village from each of the 4 study arms (4 total villages) and we evaluated the odds of ocular Chlamydia versus the rank order of presentation for examination and laboratory assessment before treatment was offered.We found the odds of harboring ocular Chlamydia dropped by more than 70% from the first child examined to the last child examined (OR 0.27, 95% CI 0.13-0.59, P = 0.001) in the 4 randomly selected villages. We found the odds of active trachoma dropped by 80% from the first child examined to the last child examined (OR 0.20, 95% CI 0.10-0.4, P

Lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths, and trachoma are the five most prevalent neglected tropical diseases in the world, and each is frequently treated with mass drug administrations. We performed a survey of neglected tropical diseases experts to elicit their opinions on the role of mass drug administrations for the elimination of these infections.We sent an online survey to corresponding authors who had published an article about a neglected tropical disease from 2007 to 2011. Of 825 unique authors who were invited to complete the survey, 365 (44.2%) responded, including 234 (28.4%) who answered questions regarding one of the five most prevalent neglected tropical diseases. Respondents had varying opinions about the goals of programmatic activities for their chosen neglected tropical disease, with elimination or eradication identified as the most important goal by 87% of lymphatic filariasis respondents, 66% of onchocerciasis respondents, 55% of trachoma respondents, 24% of schistosomiasis respondents, and 21% of soil-transmitted helminth respondents. Mass drug administrations, other non-medication health measures, and education were generally thought to be more important for elimination than vector control, development of a new tool, or the presence of a secular trend. Drug resistance was thought to be a major limitation of mass drug administrations for all five neglected tropical diseases. Over half of respondents for lymphatic filariasis and trachoma thought that repeated mass drug administrations could eliminate infection within ten years of the initiation of mass treatments.Respondents for lymphatic filariasis, onchocerciasis, and trachoma were more enthusiastic about the prospects of elimination and eradication than were respondents for schistosomiasis or soil-transmitted helminths. Mass drug administrations were generally believed to be among the most important factors for the success of elimination efforts for each of the five neglected tropical diseases, highlighting the opportunity for integrating drug distributions.

Trachoma control programs utilize mass azithromycin distributions to treat ocular Chlamydia trachomatis as part of an effort to eliminate this disease world-wide. But it remains unclear what the community-level risk factors are for infection.This cluster-randomized, controlled trial entered 48 randomly selected communities in a 2×2 factorial design evaluating the effect of different treatment frequencies and treatment coverage levels. A pretreatment census and examination established the prevalence of risk factors for clinical trachoma and ocular chlamydia infection including years of education of household head, distance to primary water source, presence of household latrine, and facial cleanliness (ocular discharge, nasal discharge, and presence of facial flies). Univariate and multivariate associations were tested using linear regression and Bayes model averaging.There were a total of 24,536 participants (4,484 children aged 0-5 years) in 6,235 households in the study. Before treatment in May to July 2010, the community-level prevalence of active trachoma (TF or TI utilizing the World Health Organization [WHO] grading system) was 26.0% (95% CI: 21.9% to 30.0%) and the mean community-level prevalence of chlamydia infection by Amplicor PCR was 20.7% (95% CI: 16.5% to 24.9%) in children aged 0-5 years. Univariate analysis showed that nasal discharge (0.29, 95% CI: 0.04 to 0.54; P = 0.03), presence of flies on the face (0.40, 95% CI: 0.17 to 0.64; P = 0.001), and years of formal education completed by the head of household (0.07, 95% CI: 0.07 to 0.13; P = 0.03) were independent risk factors for chlamydia infection. In multivariate analysis, facial flies (0.26, 95% CI: 0.02 to 0.49; P = 0.03) and years of formal education completed by the head of household (0.06, 95% CI: 0.008 to 0.11; P = 0.02) were associated risk factors for ocular chlamydial infection.We have found that the presence of facial flies and years of education of the head of the household are risk factors for chlamydia infection when the analysis is done at the community level.ClinicalTrials.gov NCT00792922.

BACKGROUND: Following an epidemiological study carried out in 2006 showing a high prevalence of blinding trachoma in the Far North Region of Cameroon, a trachoma elimination programme using the SAFE strategy was initiated: three yearly trachoma mass treatments were to be performed. METHODOLOGY/PRINCIPAL FINDINGS: The entire district population (120,000 persons) was treated with azithromycin 1.5% eye drops in February 2008 and January 2009. To assess the effect of treatment on the prevalence of active trachoma, three epidemiological studies were conducted on a representative sample of children aged between 1 and 10 years. The first study was performed just prior to the first treatment, the second just prior to the 2nd treatment and the third one, one year later. The prevalence of active forms of trachoma (TF + TI) dropped from 31.5% (95%CI 26.4-37.5) before treatment to 6.3% (95%CI 4.1-9.6) one year after first treatment; a reduction of nearly 80%. One year after the second treatment, the prevalence decreased to 3.1% (95%CI 2.0-4.9), a total reduction of 90%. Furthermore, there were no more TI cases (only TF). There was no report of serious or systemic side effects. Tolerance was excellent. CONCLUSIONS/SIGNIFICANCE: Active trachoma mass treatment with azithromycin 1.5% eye drops is feasible, well tolerated, and effective.

The development of anticancer drugs targeting both PI3K and mTOR pathways is recognized as a promising cancer therapeutic approach. In the current study, we designed and synthesized seventeen new thiazole compounds to investigate their effect on both PI3K and mTOR as well as their anti-apoptotic activity. All the synthesized thiazoles were investigated for their antiproliferative activity on a panel of 60 different cancer cell lines at the National Cancer Institute. Compounds 3b and 3e were selected for further investigation at five dose concentrations due to their effective growth inhibiting activity. Compounds 3b and 3e were further evaluated for their in vitro inhibitory activities against PI3Kα and mTOR compared to alpelisib and dactolisib, respectively as reference drugs. The inhibitory effect of compound 3b on PI3Kα was similar to alpelisib, but it showed weaker inhibitory activity on mTOR compared to dactolisib. Moreover, compound 3b exhibited significantly higher inhibitory activity compared to compound 3e against both PI3Kα and mTOR. The cell cycle analysis showed that compounds 3b and 3e induced G0-G1 phase cell cycle arrest in the leukemia HL-60(TB) cell line. Meanwhile, they significantly increased the total apoptotic activity which was supported by an increase in the level of caspase-3 in leukemia HL-60(TB) cell lines. Molecular docking experiments provided additional explanation for these results by demonstrating the ability of these derivatives to form a network of key interactions, known to be essential for PI3Kα/mTOR inhibitors. All these experimental results suggested that 3b and 3e are potential PI3Kα/mTOR dual inhibitors and could be considered promising lead compounds for the development of anticancer agents., Competing Interests: The authors have clearly stated that they do not have any conflicts of interest. The authors are solely responsible for the content and writing of this manuscript., (This journal is © The Royal Society of Chemistry.)

Breast cancer (BC) diagnoses not only present physical challenges but profoundly affect survivors' psychosocial well-being leading to sexual health challenges. This clinical practice review aimed to discuss the current literature and outline the knowledge gaps related to care for sexual health after BC, including survivors' sexual health concerns, as well as available prospective surveillance programs. Current literature on the sexual health challenges of BC survivors was identified and sorted into contributing factors, treatments and interventions, and practice recommendations. This evidence was then used to identify gaps in the literature and make recommendations for future research. BC survivors experience a variety of physical symptoms, such as pain during sex or dyspareunia, which impair sexual well-being. Additionally, dissatisfaction with sexual function may arise due to psychosocial stressors (e.g., depression or body image concerns) and the inverse may worsen psychological well-being. Treatments can have lasting effects that may impact sexual function, often reciprocally related to physical and psychosocial factors. Current treatments for sexual dysfunction involve topical products for vaginal symptoms (e.g., creams, pH-balanced gels, hyaluronic acid or vitamin E suppositories, natural oils, topical estrogen, or lubricants) and various counseling and educational interventions (e.g., mental health counseling, sex therapy, or couples-based psychotherapy). There is a general lack of research considering the ways in which intersectional concerns can impact sexual health experiences after BC. Existing studies do not often consider potential differences in needs that may arise due to ethnicity, age, or socioeconomic background. To address these limitations a significant paradigm shift in survivorship care. This requires moving beyond disease management towards a more holistic, comprehensive, patient-centered approach prioritizing comfort and sexual well-being.

Five new pyridazine scaffolds were synthesized and assessed for their inhibitory potential against both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) compared with indomethacin and celecoxib. The majority of the synthesized compounds demonstrated a definite preference for COX-2 over COX-1 inhibition. Compounds 4c and 6b exhibited enhanced potency towards COX-2 enzyme with IC 50 values of 0.26 and 0.18 µM, respectively, compared to celecoxib with IC 50  = 0.35 µM. The selectivity index (SI) of compound 6b was 6.33, more than that of indomethacin (SI = 0.50), indicating the most predominant COX-2 inhibitory activity. Consequently, the in vivo anti-inflammatory activity of compound 6b was comparable to that of indomethacin and celecoxib and no ulcerative effect was detected upon the oral administration of compound 6b, as indicated by the histopathological examination. Moreover, compound 6b decreased serum plasma PEG2 and IL-1β. To rationalize the selectivity and potency of COX-2 inhibition, a molecular docking study of compound 6b into the COX-2 active site was carried out. The COX-2 inhibition and selectivity of compound 6b can be attributed to its ability to enter the side pocket of the COX-2 enzyme and interact with the essential amino acid His90. Together, these findings suggested that compound 6b is a promising lead for the possible design of COX-2 inhibitors that could be employed as safe and effective anti-inflammatory drugs., 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 © 2024 Elsevier Inc. All rights reserved.)

Background & Objective: Cervical cancer spreads to the pelvic lymph nodes, leading to a high incidence of cancer recurrence and unfavorable survival rates. Therefore, there is an urgent need to detect new predictive biomarkers for the early assessment of pelvic lymph node status in patients with cervical cancer. The current study aimed to assess the expression of FABP4, GINS2, and CBX7 in cervical cancer tissue to detect their prognostic and predictive roles in developing lymph node metastases in patients with that cancer type., Methods: We collected the tissues from patients with cervical cancer and evaluated the expression of FABP4, GINS2, and CBX7 using immunohistochemistry. We evaluated the association between their expression and clinicopathological and prognostic parameters., Results: A high expression of FABP4 and GINS2 and a low expression of CBX7 were found to be positively associated with the old age group, large tumor size, high grade and lymphovascular involvement, para-uterine organ infiltration, advanced FIGO stage, chemotherapeutic resistance, and tumor recurrence., Conclusion: We demonstrated the oncogenic roles of FABP4 and GISN2 in addition to the on-co-suppressive roles of CBX7 in cervical cancer and their association with poor clinicopathological criteria and poor survival. Our results may indicate that FABP4, GISN2, and CBX7 could be considered predictive biomarkers of the occurrence of lymph node metastases in the cancer of the cervix preoperatively, which could be beneficial in the accurate preoperative design therapy., Competing Interests: None., (© 2024.)

Novel 3-phenyltetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives were synthesized and screened for their antiproliferative activity against a panel of 60 cancer cell lines. Derivatives 5b, 5f, and 9c showed significant antitumor activity at a single dose with mean growth inhibition of 55.62%, 55.79%, and 71.40%, respectively. These compounds were further investigated against HCT-116, colon cancer cell line, and FHC, normal colon cell line. Compound 9c showed the highest activity with IC 50  = 0.904 ± 0.03 µM and SI = 20.42 excelling doxorubicin which scored IC 50  = 2.556 ± 0.09 µM and SI = 6.19. Compound 9c was also the most potent against B-RAF WT and mutated B-RAF V600E with IC 50  = 0.145 ± 0.005 and 0.042 ± 0.002 µM, respectively in comparison with vemurafenib with IC 50  = 0.229 ± 0.008 and 0.038 ± 0.001 µM, respectively. The cell cycle analysis showed that 9c increased the cell population and induced an arrest in the cell cycle of HCT-116 cancer cells at the G0-G1 stage with 1.23-fold. Apoptosis evaluation showed that compound 9c displayed an 18.18-fold elevation in total apoptosis of HCT-116 cancer cells in comparison to the control. Compound 9c increased the content of caspase-3 by 3.52-fold versus the control. A molecular modeling study determined the binding profile and interaction of 9c with the B-RAF active site., (© 2024 Wiley Periodicals LLC.)

Haemaphysalis longicornis is a common Ixodida tick species found in temperate areas of Asian countries. An anti-tick assay was conducted on adult female H. longicornis ticks. Plant extract solutions were prepared at concentrations of 50, 25, and 10 mg/mL. Tick survival and mortality were assessed by counting the number of dead and live ticks at 24 h, 48 h, 72 h, and 96 h posttreatment. Out of 11 plant extracts screened, Artemisia judaica extract exhibited the highest potency with 100% mortality (5/5) at 48 h when applied at high and moderate concentrations (50 and 25 mg/mL). Similar results were observed at 96 h for the 10 mg/mL group compared to the untreated ticks. Cleome droserifolia extract demonstrated partial activity with 60% (3/5) and 20% (1/5) mortality at 96 h posttreatment at concentrations of 50 and 25 mg/mL, respectively. Forsskaolea tenacissima extract showed a weak effect with 100% tick mortality (5/5) only at the highest treatment concentration after 96 h. To confirm the activity of A. judaica, trial 2 was conducted. A. judaica demonstrated potency within 48 h in high dose and 72 h in moderate dose, with 100% mortality (15/15) at 96 h posttreatment compared to untreated ticks. The median lethal time 50 (LT50) values were 30.37 h for the high and 55.08 h for the moderate doses. Liquid chromatography‒mass spectrometry was performed on the most potent candidate (A. judaica) to identify its phytochemical components. The results revealed the presence of 9 compounds identified through manual annotation and 74 compounds from the Global Natural Products Social library. These compounds included terpenoids, steroids, phenylpropanoids, flavonoid glycosides, flavonoids, and benzenoids. Camphor was identified as the major component via both approaches. These findings suggest the potential use of A. judaica extract in the future development of acaricidal therapeutics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abdou 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.)

Foodborne illnesses and microbial food contamination are crucial concerns and still issues of great worldwide concern. Additionally, the serious health hazards associated with the use of chemical preservatives in food technology. Lysozyme (Lz) is an active protein against Gram-positive bacterial cell wall through its muramidase lytic activity; however, several authors could identify some antimicrobial peptides derived from Lz that have an exaggerated and broad-spectrum antibacterial activity. Therefore, a lysozyme peptides preparation (LzP) is developed to broaden the Lz spectrum. In this work, we investigated the potential efficacy of LzP as a novel Nutra-preservative (food origin) agent against some pathogenic and spoilage bacteria. Our results showed that LzP demonstrated only 11% of the lysozyme lytic activity. However, LzP exhibited strong antibacterial activity against Escherichia coli, Salmonella enteritidis, and Pseudomonas species, while Salmonella typhi and Aeromonas hydrophila exhibited slight resistance. Despite the lowest LzP concentration (0.1%) employed, it performs stronger antibacterial activity than weak organic acids (0.3%). Interestingly, the synergistic multi-component formulation (LzP, glycine, and citric acid) could inhibit 6 log 10 cfu/ml of E. coli survival growth. The effect of heat treatment on LzP showed a decrease in its antibacterial activity at 5 and 67% by boiling at 100 °C/30 min, and autoclaving at 121 °C/15 min; respectively. On the other hand, LzP acquired stable antibacterial activity at different pH values (4-7). In conclusion, LzP would be an innovative, natural, and food origin preservative to control the growth of food poisoning and spoilage bacteria in food instead chemical one., (© 2024. The Author(s).)

Aim: Novel thiazole hybrids were synthesized via thiazolation of 4-phenylthiosemicarbazone ( 4 ). Materials & methods: The anticancer activity against the NCI 60 cancer cell line panel. Results: Methyl 2-(2-((1-(naphthalen-2-yl)ethylidene)hydrazineylidene)-4-oxo-3-phenylthiazolidin-5-ylidene)acetate ( 6a ) showed significant anticancer activity at 10 μM with a mean growth inhibition (GI) of 51.18%. It showed the highest cytotoxic activity against the ovarian cancer OVCAR-4 with an IC 50 of 1.569 ± 0.06 μM. Compound 6a inhibited PI3Kα with IC 50  = 0.225 ± 0.01 μM. Moreover, compound 6a revealed a decrease of Akt and mTOR phosphorylation in OVCAR-4 cells. In addition, antibacterial activity showed that compounds 11 and 12 were the most active against Staphylococcus aureus . Conclusion: Compound 6a is a promising molecule that could be a lead candidate for further studies.

New thieno[2,3-d]pyrimidine derivatives were designed and synthesized. The National Cancer Institute (NCI) evaluated the synthesized novel compounds against a panel of 60 tumor cell lines for their antiproliferative activity. Compounds 6b, 6f, and 6g showed potent anticancer activity at 10 µM dose, with mean GI of 20.86%, 76.41%, and 31.49%, respectively. Compound 6f was selected for five-dose concentrations evaluation. Compound 6f scored a submicromolar range of GI 50 values against 10 cancer cell lines, indicating broad-spectrum and potent antiproliferative activity. Compound 6f TGI values were recorded in the cytostatic range of 4.02-95.1 µM. In comparison to sorafenib, the tested compounds 6b, 6f, and 6g inhibited VEGFR-2 with IC 50 values of 0.290 ± 0.032, 0.066 ± 0.004, and 0.16 ± 0.006 µM, correspondingly. Compound 6f significantly reduced the total VEGFR-2 expression and its phosphorylation. Additionally, 6f reduced the phosphorylation of PI3K, Akt, and mTOR pathway proteins. Moreover, the migratory potential of HUVECs was significantly reduced, after 72 h of treatment with compound 6f, resulting in disrupted wound healing patterns which verified the angiogenesis suppression properties of compound 6f. Compound 6f increased the total apoptosis percentage by 21.27-fold compared to sorafenib, which caused a 24.11-fold increase in the total apoptosis percentage. This apoptotic activity was accompanied by a 7.81-fold increase in the level of apoptotic caspase-3. Furthermore, the cell cycle analysis revealed that the target derivative 6f reduced cellular proliferation and induced an arrest in HCT-15 colon cancer cell cycle at the S phase. Molecular modeling was used to determine the binding profile and affinity of derivative 6f toward the VEGFR-2 active site., (© 2023 Wiley Periodicals LLC.)

Two series of quinazolinone derivatives were designed and synthesized as dihydrofolate reductase (DHFR) inhibitors. All compounds were evaluated for their antibacterial and antitumor activities. Antibacterial activity was evaluated against three strains of Gram-positive and Gram-negative bacteria. Compound 3d exhibited the highest inhibitory activity against Staphylococcus aureus DHFR (SaDHFR) with IC 50 of 0.769 ± 0.04 μM compared to 0.255 ± 0.014 μM for trimethoprim. Compound 3e was also more potent than trimethoprim against Escherichia coli DHFR (EcDHFR) with IC 50 of 0.158 ± 0.01 μM and 0.226 ± 0.014 μM, respectively. Compound 3e exhibited a promising antiproliferative effect against most of the tested cancer cells. It also showed potent activity against leukemia (CCRF-CEM, and RPMI-8226); lung NCI-H522, and CNS U251 with GI% of 65.2, 63.22, 73.28, and 97.22, respectively. The cytotoxic activity of compound 3e was almost half the activity of doxorubicin against CCRF-CEM cell line with IC 50 of 1.569 ± 0.06 μM and 0.822 ± 0.03 µM, respectively. In addition, compound 3e inhibited human DHFR with IC 50 value of 0.527 ± 0.028 µM in comparison to methotrexate (IC 50  = 0.118 ± 0.006 µM). Compound 3e caused an arrest of the cell cycle mainly at the S phase and caused a rise in the overall apoptotic percentage from 2.03% to 48.51%. (23.89-fold). Treatment of CCRF-CEM cells with compound 3e produced a significant increase in the active caspase-3 level by 6.25-fold compared to untreated cells. Molecular modeling studies were performed to evaluate the binding pattern of the most active compounds in the bacterial and human DHFR., (© 2023 Wiley Periodicals LLC.)

Strontium borosilicate bioactive glass (SrBG) and calcium aluminate cement (CA) composites have been synthesized. The primary goal of this work is to evaluate how SrBG affects the bioactivity and physico-mechanical characteristics of CA. To fulfill this aim, SrBG was prepared by melt-quenching method and utilized as a substitute for CA by 5, 10, 15, and 20 wt%. To estimate the biological behavior of the prepared specimens, hydrᴏxyapatite layer (HA) establishment on the surface of cement paste was followed; after their immersion in a solution resembles human blood plasma (simulated body fluid solution (SBF)) at a temperature of about37 ± 0.5 °C for 4 weeks. The variations of pH, Ca and P ions concentrations in the SBF solution after soaking were determined. Compressive strength, apparent porosity, and bulk density were also measured. Via Fourier transform IR spectroscopy and X-ray diffraction analyses, the main components had been analyzed. Using scanning electron microscope (SEM) attached to energy dispersive spectroscopy, morphology of the samples was investigated. Additionally, the antimicrobial property was also assessed. The results proved that the hydrᴏxyapatite layer (HA) was developed on the surface of the prepared samples after soaking in the biological solution (SBF). It was also found that increasing SrBG percent in synthesized samples promotes the physico-mechanical characteristics and also the bioactivity performance of CA cement. Finally, these materials also showed good inhibition behavior towards bacterial biᴏfilms, against S. aureus and E. coli. after 48h. This makes these materials excellent candidates for preventing growth of bacteria after their implantation in teeth or bone., 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 Elsevier Ltd. All rights reserved.)

Objective: Myomectomy is the preferred surgical approach to manage uterine fibroids. However, uterine fibroids are highly vascular tumors and, consequently, extremely susceptible to problems from myomectomy-related hemorrhage. Hence, we aim to compare oxytocin efficacy and safety profile versus tranexamic acid (TA) with ethamsylate for reducing bleeding during myomectomy., Methods: This randomized, double-blinded multicenter study was performed between 20 th August 2020 and 20 th October 2020 at El-Galaa Teaching Hospital, El Hussein University Hospital, Al-Azhar University Hospitals of Assiut, and Al-Azhar University Hospitals of Damietta. One hundred and eighty patients were enrolled and divided into three groups: group (1) received an injection of 30 IU of oxytocin in 500 ml of normal saline; group (2) received injections of 1 g of TA, 250 mg of Ethamsylate, and 110 ml of normal saline IV; and group (3) received an injection of 110 ml of normal saline IV just before surgical incision., Results: In 180 premenopausal women, oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy (666.25 ± 183.03, 630.72 ± 145.83, and 646.67 ± 168.92, respectively (P = 0.506)). Non-significant trends were observed for a reduction in operation time (P = 0.760), intra/postoperative blood transfusion (P = 0.624), hospital stay (P = 0.986), postoperative fever (P = 0.659), and wound infection (P = 1)., Conclusion: Oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy which opens a new question about the role of the use of the hemostatic drug during myomectomy especially in centers with limited resources and had higher rates., Trial Registration: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202008739887429 and was approved on 24/08/2020., (© 2023. The Author(s).)

A series of coumarin derivatives were designed, synthesized, and evaluated for their antiproliferative activity. Compound 3e exhibited significant antiproliferative activity and was further evaluated at five doses at the National Cancer Institute. It effectively inhibited vascular endothelial growth factor receptor-2 (VEGFR-2) with an IC 50 value of 0.082 ± 0.004 µM compared with sorafenib. While compound 3e significantly downregulated total VEGFR-2 and its phosphorylation, it markedly reduced the HUVEC's migratory potential, resulting in a significant disruption in wound healing. Furthermore, compound 3e caused a 22.51-fold increment in total apoptotic level in leukemia cell line HL-60(TB) and a 6.91-fold increase in the caspase-3 level. Compound 3e also caused cell cycle arrest, mostly at the G1/S phase. Antibacterial activity was evaluated against Gram-positive and Gram-negative bacterial strains. Compound 3b was the most active derivative, with the same minimum inhibitory concentration and minimum bactericidal concentration value of 128 μg/mL against K. pneumonia and high stability in mammalian plasma. Moreover, compounds 3b and 3f inhibited Gram-negative DNA gyrase with IC 50  = 0.73 ± 0.05 and 1.13 ± 0.07 µM, respectively, compared to novobiocin with an IC 50 value of 0.17 ± 0.02 µM. The binding affinity and pattern of derivative 3e toward the VEGFR-2 active site and compounds 3a-c and 3f in the DNA gyrase active site were evaluated using molecular modeling. Overall, ADME studies of the synthesized coumarin derivatives displayed promising pharmacokinetic properties., (© 2023 Wiley Periodicals LLC.)

Background: This study aimed to evaluate the results of posterior component separation (CS) and transversus abdominis muscle release (TAR) with retro-muscular mesh reinforcement in patients with primary abdominal wall dehiscence (AWD). The secondary aims were to detect the incidence of postoperative surgical site occurrence and risk factors of incisional hernia (IH) development following AWD repair with posterior CS with TAR reinforced by retromuscular mesh., Methods: Between June 2014 and April 2018, 202 patients with grade IA primary AWD (Björck's first classification) following midline laparotomies were treated using posterior CS with TAR release reinforced by a retro-muscular mesh in a prospective multicenter cohort study., Results: The mean age was 42 ± 10 years, with female predominance (59.9%). The mean time from index surgery (midline laparotomy) to primary AWD was 7 ± 3 days. The mean vertical length of primary AWD was 16 ± 2 cm. The median time from primary AWD occurrence to posterior CS + TAR surgery was 3 ± 1 days. The mean operative time of posterior CS + TAR was 95 ± 12 min. No recurrent AWD occurred. Surgical site infections (SSI), seroma, hematoma, IH, and infected mesh occurred in 7.9%, 12.4%, 2%, 8.9%, and 3%, respectively. Mortality was reported in 2.5%. Old age, male gender, smoking, albumin level < 3.5 gm%, time from AWD to posterior CS + TAR surgery, SSI, ileus, and infected mesh were significantly higher in IH. IH rate was 0.5% and 8.9% at two and three years, respectively. In multivariate logistic regression analyses, the predictors of IH were time from AWD till posterior CS + TAR surgical intervention, ileus, SSI, and infected mesh., Conclusion: Posterior CS with TAR reinforced by retro-muscular mesh insertion resulted in no AWD recurrence, low IH rates, and low mortality of 2.5%. Trial registration Clinical trial: NCT05278117., (© 2023. The Author(s).)

Strongylid and non-strongylid nematodes are one of the most important parasites infecting equines. The traditional method to identify these nematodes is through coproscopy and fecal culture. Because of the scarcity of data published in Egypt discussing the morphometric features of infective 3 rd larvae of these nematodes, this study aims to provide a morphometric key for L3 of common strongylid and non-strongylid nematodes infecting Egyptian equines. For this reason, we cultured fecal samples containing GINs eggs and 3 rd larval stages were identified based on their morphology (i.e., shape and number of intestinal cells (IC), shape of the esophagus, and shape of the tail sheath) in addition to computing their dimensions (i.e., length of larvae with sheath, length of the esophagus, length of intestinal cells, and body breadth). We identified 3 rd larval stages of four strongylid nematodes (Cyathostomum sensu lato, Strongylus vulgaris, Strongylus equinus, and Strongylus edentatus) as well as two non-strongylid nematodes (Strongyloides westeri, and Trichostrongylus axei). Statistically, our results revealed significant differences in terms of total length, body width, esophagus length, and gut length among 3 rd larvae identified in the current study. The combination of both morphological and metric keys will allow the better identification of common strongylid and non-strongylid nematodes infecting equines., (© 2022. The Author(s).)

Novel halogenated phenoxychalcones 2a-f and their corresponding N -acetylpyrazolines 3a-f were synthesised and evaluated for their anticancer activities against breast cancer cell line (MCF-7) and normal breast cell line (MCF-10a), compared with staurosporine. All compounds showed moderate to good cytotoxic activity when compared to control. Compound 2c was the most active, with IC 50 = 1.52 µM and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC 50 = 1.87 µM and selectivity index = 11.03. Compound 2c decreased both total mitogen activated protein kinase (p38α MAPK) and phosphorylated enzyme in MCF-7 cells, suggesting its ability to decrease cell proliferation and survival. It also showed the ability to induce ROS in MCF-7 treated cells. Compound 2c exhibited apoptotic behaviour in MCF-7 cells due to cell accumulation in G2/M phase and elevation in late apoptosis 57.78-fold more than control. Docking studies showed that compounds 2c and 2f interact with p38alpha MAPK active sites.

Nineteen new quinazolin-4(3 H )-one derivatives 3a-g and 6a-l were designed and synthesised to inhibit EGFR. The antiproliferative activity of the synthesised compounds was tested in vitro against 60 different human cell lines. The most potent compound 6d displayed superior sub-micromolar antiproliferative activity towards NSC lung cancer cell line NCI-H460 with GI 50 = 0.789 µM. It also showed potent cytostatic activity against 40 different cancer cell lines (TGI range: 2.59-9.55 µM). Compound 6d potently inhibited EGFR with IC 50 = 0.069 ± 0.004 µM in comparison to erlotinib with IC 50 value of 0.045 ± 0.003 µM. Compound 6d showed 16.74-fold increase in total apoptosis and caused cell cycle arrest at G1/S phase in breast cancer HS 578T cell line. Moreover, the most potent derivatives were docked into the EGFR active site to determine their binding mode and confirm their ability to satisfy the pharmacophoric features required for EGFR inhibition.

Background: Worldwide, COVID-19 greatly reduced healthcare accessibility and utilization by non-COVID patients including cancer. This study aimed to quantify and characterize cancer care adjustments experienced by cancer patients/survivors; and to explore their concerns, beliefs, and knowledge regarding COVID-19., Methods: A cross-sectional study was conducted using a questionnaire distributed through social media patients' groups (June-December 2020). Questionnaire included basic information, care adjustments (in "care provision" and in "treatment plan"), and patients' concerns, beliefs, and knowledge. Data description and analysis were done., Results: Out of 300 participants, there were 68.0% on-treatment and 32.0% in follow-up stage. Care adjustments were reported by 29.7%; mostly in care provision (27.3%) rather than treatment plan (4.9%). Adjustments were less likely to occur when healthcare facility was in governorate other than that of residence (OR:0.53, 95%CI:0.30-0.96, P = 0.037) and more likely with long-standing diagnosis (≥12 months) compared with recent (<3 months) (adjusted-OR:4.13, 95%CI:1.19-14.34, P = 0.026). Lower proportion of on-treatment patients used remote consultation than patients in follow-up [4.4% versus 17.7%, P < 0.001]. Patients were concerned about fulfilling their care visits more than the probable COVID-19 infection (72.3%). It was uncommon to feel that the risk of COVID-19 infection is higher in care places than in the community (27.3%) or to feel safe with remote consultations (34.3%). However, patients increased their infection control practice (64.0%) and the majority were aware of their increased susceptibility to complications (86.0%). Somewhat, they were also concerned about the care quality (57.3%). Many had adequate access to COVID-19 information (69.0%) and their main sources were the Ministry of Health webpage and ordinary media (radio/TV)., Conclusion: Cancer patients were primarily concerned about fulfilling their planned care and COVID-19 infection was less appreciated., Policy Summary: Launching of a policy for enhancement of telemedicine experience through more patients' engagement-as essential stakeholders-may be required. To heighten pandemic resilience for cancer care in Egypt, more investment in establishing specialized end-to-end cancer care facilities that ensure continuity of care may be justified., Competing Interests: Declarations of interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Microbial exopolysaccharides (EPSs) extracted from lactic acid bacteria (LAB) are generally recognized as safe. They have earned popularity in recent years because of their exceptional biological features. Therefore, the present study main focus was to study EPS-production from probiotic LAB and to investigate their antioxidant and burn wound healing efficacy. Seventeen LAB were isolated from different food samples. All of them showed EPS-producing abilities ranging from 1.75 ± 0.05 to 4.32 ± 0.12 g/l. RO30 isolate (from Romi cheese) was chosen, due to its ability to produce the highest EPS yield (4.23 ± 0.12 g/l). The 16S rDNA sequencing showed it belonged to the Lactiplantibacillus plantarum group and was further identified as L. plantarum RO30 with accession number OL757866. It displayed well in vitro probiotic properties. REPS was extracted and characterized. The existence of COO - , OH and amide groups corresponding to typical EPSs was confirmed via FTIR. It was constituted of glucuronic acid, mannose, glucose, and arabinose in a molar ratio of 2.2:0.1:0.5:0.1, respectively. The average molecular weight was 4.96 × 10 4  g/mol. In vitro antioxidant assays showed that the REPS possesses a DPPH radical scavenging ability of 43.60% at 5 mg/ml, reducing power of 1.108 at 10 mg/ml, and iron chelation activity of 72.49% and 89.78% at 5 mg/ml and 10 mg/ml, respectively. The healing efficacy of REPS on burn wound models in albino Wistar rats showed that REPS at 0.5% (w/w) concentration stimulated the process of healing in burn areas. The results suggested that REPS might be useful as a burn wound healing agent., (© 2022. The Author(s).)

The GC-MS analysis of tea tree oil (TTO) revealed 38 volatile components with sesquiterpene hydrocarbons (43.56%) and alcohols (41.03%) as major detected classes. TTO efficacy is masked by its hydrophobicity; nanoencapsulation can address this drawback. The results showed that TTO-loaded solid lipid nanoparticles (SLN1), composed of glyceryl monostearate (2% w/w ) and Poloxamer188 (5% w/w ), was spherical in shape with a core-shell microstructure. TTO-SLN1 showed a high entrapment efficiency (96.26 ± 2.3%), small particle size (235.0 ± 20.4 nm), low polydispersity index (0.31 ± 0.01), and high negative Zeta potential (-32 mV). Moreover, it exhibited a faster active agent release (almost complete within 4 h) compared to other formulated TTO-SLNs as well as the plain oil. TTO-SLN1 was then incorporated into cellulose nanofibers gel, isolated from sugarcane bagasse, to form the 'TTO-loaded nanolipogel' which had a shear-thinning behavior. Second-degree thermal injuries were induced in Wistar rats, then the burned skin areas were treated daily for 7 days with the TTO-loaded nanolipogel compared to the unmedicated nanolipogel, the TTO-loaded conventional gel, and the normal saline (control). The measurement of burn contraction proved that TTO-loaded nanolipogel exhibited a significantly accelerated skin healing, this was confirmed by histopathological examination as well as quantitative assessment of inflammatory infiltrate. This study highlighted the success of the proposed nanotechnology approach in improving the efficacy of TTO used for the repair of skin damage induced by burns.

A series of novel thieno[2,3-d]pyrimidine derivatives was designed and synthesized based on multitarget directed drug design strategy. All the newly synthesized compounds were evaluated for their antiproliferative activity in the National Cancer Institute (NCI) against a panel of 60 tumor cell lines. Compounds 4a and 4b showed a significant antiproliferative activity at 10 µM dose, and were accordingly evaluated at five dose concentrations. They showed potent and broad-spectrum antiproliferative activity, with GI 50 values in the micromolar range of 1.44-6.93 µM and 1.66-5.82 µM, respectively. They also showed TGI values in the cytostatic range of 3.49-97.3 µM and 3.33-77.3 µM respectively. These two compounds potently inhibited VEGFR-2 with IC 50  = 0.111 ± 0.006 and 0.049 ± 0.003 µM, BRAF V600E with IC 50  = 0.089 ± 0.005 and 0.063 ± 0.003 µM and BRAF WT IC 50  = 0.071 ± 0.004 and 0.05 ± 0.003 µM, respectively in comparison to sorafenib IC 50 values of 0.031 ± 0.002, 0.035 ± 0.002 and 0.021 ± 0.001 µM against VEGFR-2, BRAF V600E and BRAF WT , respectively. Compounds 4a and 4b showed also potent down-regulation of total VEGFR-2 and phosphorylated VEGFR-2. In addition, the HUVECs migratory potential was greatly reduced resulting in significantly disrupted wound healing patterns after treatment with compounds 4a and 4b for 72 h. Furthermore, Compounds 4a and 4b induced apoptosis by 22.82- and 25.81-fold increase in the total apoptosis percentage in breast cancer MCF7 cell line. This apoptotic activity was supported by an increase in the level of apoptotic caspase-9 by 6.17- and 9.07-fold, respectively. Moreover, the cell cycle analysis showed that compounds 4a and 4b arrested the cell cycle mainly in the G1 and G1/S phases, respectively. The molecular modeling studies were performed to assess the binding pattern and affinity of derivatives 4a and 4b toward the VEGFR-2 and BRAF active sites., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Neosporosis is a parasitic disease affecting the health of dogs and cattle worldwide. It is caused by Neospora caninum, an obligate intracellular apicomplexan parasite. Dogs are its definitive host, it mostly infects livestock animals, especially cattle that acts as intermediate host. It is necessary to have well-established models of abortion and vertical transmission in experimental animals, in order to determine basic control measures for the N. caninum infection. We evaluated the role of N. caninum dense granule antigen 7 (NcGRA7) in the vertical transmission of N. caninum using the C57BL/6 pregnant mouse model. We inoculated mice on day 3.5 of pregnancy with parental Nc-1 or NcGRA7-deficient parasites (NcGRA7KO). Post-mortem analyses were performed on day 30 after birth and the surviving pups were kept until day 30 postpartum. The number of parasites in the brain tissues of offspring from NcGRA7KO-infected dams was significantly lower than that of the Nc-1-infected dams under two infection doses (1 × 10 6 and 1 × 10 5 tachyzoites/mouse). The vertical transmission rates in the NcGRA7KO-infected group were significantly lower than those of the Nc1-infected group. To understand the mechanism by which the lack of NcGRA7 decreases the vertical transmission, pregnant mice were sacrificed on day 13.5 of pregnancy (10 days after infection), although parasite DNA was detected in the placentas, no significant difference was found between the two parasite lines. Histopathological analysis revealed a greater inflammatory response in the placentas from NcGRA7KO-infected dams than in those from the parental strain. This finding correlates with upregulated chemokine mRNA expression for CCL2, CCL8, and CXCL9 in the placentas from the NcGRA7KO-infected mice. In conclusion, these results suggest that loss of NcGRA7 triggers an inflammatory response in the placenta, resulting in decreased vertical transmission of N. caninum., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Wild medicinal plants have been traditionally used as antimicrobial agents. Here, we evaluated the in vitro activity of extracts from wild Egyptian desert plants against Toxoplasma gondii and Neospora caninum. From 12 plant extracts tested, the methanolic extracts from Artemisia judaica, Cleome droserifolia, Trichodesma africanum, and Vachellia tortilis demonstrated potent activity against the growth of T. gondii, with half-maximal inhibitory concentrations (IC 50 s) of 2.1, 12.5, 21.8, and 24.5 µg/ml, respectively. C. droserifolia, an ethanolic extract of P. undulata, T. africanum, A. judaica, and V. tortilis demonstrated potent efficacy against N. caninum, with mean IC 50 s of 1.0, 3.0, 3.1, 8.6, and 17.2 µg/ml, respectively. Our data suggest these extracts could provide an alternative treatment for T. gondii and N. caninum infections.

Background: Medicinal plants have been successfully used as an alternative source of drugs for the treatment of microbial diseases. Finding a novel treatment for malaria is still challenging, and various extracts from different wild desert plants have been reported to have multiple medicinal uses for human public health, this study evaluated the antimalarial efficacy of several Egyptian plant extracts., Methods: We assessed the cytotoxic potential of 13 plant extracts and their abilities to inhibit the in vitro growth of Plasmodium falciparum (3D7), and to treat infection with non-lethal Plasmodium yoelii 17XNL in an in vivo malaria model in BALB/c mice., Results: In vitro screening identified four promising candidates, Trichodesma africanum, Artemisia judaica, Cleome droserifolia, and Vachellia tortilis, with weak-to-moderate activity against P. falciparum erythrocytic blood stages with mean half-maximal inhibitory concentration 50 (IC 50 ) of 11.7 μg/ml, 20.0 μg/ml, 32.1 μg/ml, and 40.0 μg/ml, respectively. Their selectivity index values were 35.2, 15.8, 11.5, and 13.8, respectively. Among these four candidates, T. africanum crude extract exhibited the highest parasite suppression in a murine malaria model against P. yoelii., Conclusion: Our study identified novel natural antimalarial agents of plant origin that have potential for development into therapeutics for treating malaria., (© 2022. The Author(s).)

Surgeons face great challenges in acquiring high-performance imaging because fluorescence probes with desired thermal stability remains rare. Here, hybrid lead sulfide/zinc sulfide quantum dots (PbS/ZnS QDs) nanostructures emitting in the long-wavelength end of the second near-infrared (NIR-IIb) window were synthesized and conjugated with Ribonuclease-A (RNase A). Such formed RNase A@PbS/ZnS QDs exhibited strong NIR IIb fluorescence and thermal stability, as supported by the photoluminescent emission assessment at different temperatures. This will allow the RNase A@PbS/ZnS QDs to provide stable fluorescence signals for long-time intraoperative imaging navigation, despite often happened, undesirable thermal accumulation in vivo. Compared to NIR-IIa fluorescence imaging, NIR-IIb vascular fluorescence imaging achieved larger penetration depth, higher signal/background ratios and nearly zero endogenous tissue autofluorescence. Moreover, these QDs illustrate the reliability during the real-time and long-time precise assessment of flap perfusion by clearly visualizing microvasculature map. These findings contribute to intraoperative imaging navigation with higher precision and lower risk., (© 2022. The Author(s).)