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In-silico assessment of the potential impact of missense SNPs in SYNE4 and SUN1 on the LINC complex and their association with hearing loss

The LINC complex plays a significant role in the auditory system, as it participates in maintaining proper positioning and survival of the nucleus within the outer hair cells. To investigate the potential effect of mutations on the LINC complex structure and its association with hearing loss, we used a computational approach to analyze missense SNPs in SYNE4 and SUN1 genes, which encode Nesprin4 and SUN1 proteins, respectively. SNPs were collected from the Ensembl database and subsequently subjected to various prediction tools, such as SIFT, Polyphen2, MetaRNN, Mutation Taster, Provean, BayesDel_addAF, M-CAP, and MetaRL. Then, the UCSF chimera was used for the introduction of a corresponding amino acid substitution in each protein. HADDOCK 2.4 executed a molecular docking, the protein–protein interaction was driven by PRODIGY, and the conservation state was determined using ConSurf. Finally, a molecular dynamics simulation using Gromacs (2019.3) software was executed for the LINC complexes that correspond to the most deleterious variants for both genes. Our findings show that specific variants in SYNE4 (C381F) and SUN1 (D735Y, D735G, R761W, and C773R) significantly affect the structural integrity of the LINC complex, leading to observable destabilization. These variants are predicted to have a damaging effect on hearing ability. The bioinformatics tools employed in this study consistently predicted these variants as highly structurally affected. However, further investigations are necessary to establish a more comprehensive understanding of the precise implications of these alterations on human auditory function.

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Insuffisance cardiaque aiguë à fraction d’éjection altérée : signes électrocardiographiques associés à la mortalité à l'institut de cardiologie d'Abidjan

IntroductionHeart failure with impaired ejection fraction (HFIEF) represents the end-stage of most cardiac diseases, and is responsible for a high mortality rate. In order to identify patients at risk, numerous clinical and paraclinical prognostic factors have been proposed. The electrocardiogram (ECG), easy to perform and inexpensive, retains a powerful role in the prognostic evaluation of heart failure patients. The aim was to evaluate ECG signs associated with mortality in a retrospective cohort of patients with ICFEA. MethodologyThe study was observational and analytical based on retrospective data collected from patients benefiting from a primary hospitalization for ICFEA at the Abidjan Heart Institute from January 2018 to July 2020. ResultsOf the 370 patients included, 197 had died by August 1, 2020, representing an overall mortality of 53%. Mortality progressed gradually up to one year, then remained unchanged up to 30 months.In multivariate Cox regression including ECG variables only, the presence of intra-ventricular conduction disorders (OR: 1.80; 95% CI [1.01–3.25]), microvoltage (OR: 1.82; 95% CI [1.05–16]), and pathological Q waves (OR: 1.70; 95% CI [1.02–2.83]), were significantly associated with overall mortality. When ECG variables and clinical, paraclinical and therapeutic demographic variables were included, only the presence of pathological Q waves (OR:1.74; 95% CI [1.01–3.01]) persisted as a risk factor for mortality. Hypertension and treatment of heart failure, in particular ACEI/ARII, beta-blockers and ARM, were protective factors. The presence of Q waves was associated with a significant reduction in survival, based on curves obtained using the Kaplan-Meier model. ConclusionICFEA is responsible for high mortality, mainly in the year following the 1st hospitalization for cardiac decompensation. The presence of pathological Q waves is the only electrocardiographic sign that remains statistically associated with a poor prognosis, after adjustment.

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High-risk human papillomavirus distribution according to human immunodeficiency virus status among women with cervical cancer in Abidjan, Côte d'Ivoire, 2018 to 2020.

As human papillomavirus (HPV) immunisation and HPV-based cervical cancer (CC) screening programmes expand across sub-Saharan Africa, we investigated the potential impact of human immunodeficiency virus (HIV) status on high-risk (HR)-HPV distribution among women with CC in Côte d'Ivoire. From July 2018 to June 2020, paraffin-embedded CC specimens diagnosed in Abidjan, Côte d'Ivoire were systematically collected and tested for HR-HPV DNA. Type-specific HR-HPV prevalence was compared according to HIV status. Of the 170 CC specimens analysed (median age 52 years, interquartile range: [43.0-60.0]), 43 (25.3%) were from women living with HIV (WLHIV) with a median CD4 count of 526 [373-833] cells/mm3 and 86% were on antiretroviral therapy (ART). The overall HR-HPV prevalence was 89.4% [95% CI: 84.7-94.1]. All were single HR-HPV infections with no differences according to HIV status (P = .8). Among HR-HPV-positive CC specimens, the most prevalent HR-HPV types were HPV16 (57.2%), HPV18 (19.7%), HPV45 (8.6%) and HPV35 (4.6%), with no significant differences according to HIV status. Altogether, infection with HPV16/18 accounted for 71.1% [95% CI: 55.9-86.2] of CC cases in WLHIV vs 78.9% [95% CI: 71.3-86.5] in women without HIV (P = .3). The study confirms the major role of HPV16/18 in CC in Côte d'Ivoire and should support a regional scale-up of HPV16/18 vaccination programmes regardless of HIV status. However, vaccines targeting additional HR-HPV types, including HPV45 and HPV35, could further decrease future CC incidence in Côte d'Ivoire, both for WLHIV and women without HIV.

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Knowledge and practices of private pharmacy auxiliaries on malaria in Abidjan, Côte d’Ivoire

BackgroundThe emergence of resistance to artemisinin derivatives in Southeast Asia constitutes a serious threat for other malaria endemic areas, particularly in Côte d’Ivoire. To delay this resistance, the application of the control measures recommended by the National Malaria Control Programme (NMCP) for a correct management, in the private pharmacies, is a necessity. The purpose of this study was, therefore, to assess the level of knowledge and practices of private pharmacy auxiliary in Abidjan about the management of malaria.MethodsA descriptive cross-sectional study was conducted from April to November 2015. It included auxiliaries of private pharmacies in Abidjan. Data collection material was a structured an open pretested questionnaire. Data analysis was carried out using Package for Social Science (SPSS) software version 21.1. Chi square test was used to compare proportions for a significance threshold of 0.05 for the p value.ResultsA total, 447 auxiliaries from 163 private pharmacies were interviewed. It was noted that the auxiliaries had a good knowledge of clinical signs of uncomplicated malaria (99.1%), biological examinations (54.6% for the thick film and 40.7% for rapid diagnostic tests (RDTs) and anti-malarial drugs (99.3% for artemether + lumefantrine, AL). The strategies of vector control (long-lasting insecticide-treated mosquito nets (LLITNs, Repellent ointments, cleaning gutters, elimination of larvae breeding site and intermittent preventive treatment with sulfadoxine–pyrimethamine (IPTp-SP) in pregnant women were also known by the auxiliaries, respectively 99.8% and 77.4%. However, the malaria pathogen (25.1%) and the NMCP recommendations (e.g. use of AL or AS + AQ as first-line treatment for uncomplicated malaria and IPTp-SP in pregnant women) were not well known by the auxiliaries (28.2% and 26.9% for uncomplicated and severe malaria). Concerning the practices of the auxiliaries, 91.1% offered anti-malarial drugs to patients without a prescription and 47.3% mentioned incorrect dosages. The combination artemether + lumefantrine was the most recommended (91.3%). The delivery of anti-malarial drugs was rarely accompanied by advice on malaria prevention, neither was it carried out on the result of an RDT.ConclusionThe epidemiology and the NMCP recommendations for the diagnostic and therapeutic management of malaria, are not well known to auxiliaries, which may have implications for their practices. These results show the need to sensitize and train private pharmacy auxiliaries, and also to involve them in NMCP activities.

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