EPIDEMIOLOGIE DE L’HYPERTENSION ARTERIELLE EN TUNISIE.Etude Hammam Sousse/Sahloul Heart Study (HSHS)

Introduction: Tunisia is experiencing a double burden of morbidity, characterized by the explosion of cardiovascular diseases and their risk factors including arterial Hypertension. The objective of this study, based on the HSHS cohort (Hammam Sousse Sahloul Heart Study), was to determine the prevalence of hypertension in the general population and to identify its predisposing factors. Methods: HSHS is a cardiovascular health promotion initiative in the city of Hammam Sousse (Tunisia). The study was conducted via a random sample of households, using the WHO PEV technique, made up of 33 clusters, of 33 households each. All people aged 20 and over, included, benefited from a questionnaire, a physical examination and a biological assessment. The Systolic Blood Pressure (SBP) and the Diastolic Blood Pressure (DBP) were measured from the average of the last two measurements, by an OMRON type tensiometer, of suitable width. These prevalences were adjusted according to sex and age group, by their weighting coefficients in the general population, and they were accompanied by their 95% CIs. Binary logistic regression was conducted to identify independent factors associated with hypertension. Results: The study population was composed of 481 men (33.4%) and 960 women (66.6%), with an average age of 49.6±16.35 years in males (M) and 46.6±16.18 in females (F). In addition to the family history of hypertension, the sufficient weekly consumption of vegetables and fruits was low (M: 32.4%, F: 24.9%). The adjusted rate of hypertension in the adult study population was 32.5%, 95%CI[31.9-33.1] (M: 36.4%, 95%CI[35, 5-37.3]; F: 28.4%; 95% CI[27.6-29.2]), reaching in the age group of 60 years and above: M: 74.6% (95%CI[66.9-82.3], F: 82.7% (95%CI[73.8-83.6]) Multivariate analysis identified five independent factors significantly associated with hypertension: male sex (ORa=1.55 [1.18-2.03]), age over 40 years (ORa=6.54[4.70-9.11]), low level of schooling (ORa=1.80 [1.36-2.38]), low physical activity (ORa=1.42[1.07-1.88]) and high socio-economic level (ORa=1 .84 [1.30-2.63]). Conclusion: The HSHS study confirmed the high prevalence of hypertension, and the extent of its low detection and control. Hence the need for a universal approach to health promotion, oriented towards the general population, piloted by its local organizations, based on the adoption of a healthy lifestyle, and centered on physical activity.     

DNA methylation changes measured in pre‐diagnostic peripheral blood samples are associated with smoking and lung cancer risk

DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre‐diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case‐control study nested within the EPIC‐Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case‐control pairs). We validated the top signals in 429 case‐control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p‐value_pooled = 4 × 10^?17), cg03636183 in the F2RL3 gene (p‐value_pooled = 2 × 10 ^{? 13}), cg21566642 and cg05951221 in 2q37.1 (p‐value_pooled = 7 × 10^?16 and 1 × 10^?11 respectively), cg06126421 in 6p21.33 (p‐value_pooled = 2 × 10^?15) and cg23387569 in 12q14.1 (p‐value_pooled = 5 × 10^?7). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p‐values_{heterogeneity} ≤ 1.8 x10 ^{? 7}), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p‐values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack‐years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk.     

Genetic association study between T-786C NOS3 polymorphism and essential hypertension in an Algerian population of the Oran city

BackgroundEssential hypertension is an important risk factor for the development of cardiovascular disease. Important candidate genes such as NOS3 gene have been widely studied and reported to be associated with essential hypertension (HTN) in human populations.AimWe aim in this study to analyze the relationship between NOS3 -786T/C, a common genetic variant and HTN in a sample of the Algerian population of the Oran city.MethodsA case-control study has been performed in 154 subjects including 77 hypertensives and 77 normotensives. The recruitment of these subjects was done in local Health Centers of the city of Oran, West Algeria. HTN was defined as elevated systolic blood pressure SBD$\ge$140 mmHg and or sustained diastolic blood pressure DBP≥90 mmHg, measured using an Omron^® Automatic BP Monitor - M-3W machine. Consents were obtained from all participants. Polymerase chain reaction (PCR) combined with restrictive fragment length polymorphism (RFLP) was used to genotype the NOS -786T/C variant.ResultsThe distribution of the allelic frequencies did not differ between cases and controls (OR = 1.48; 95%CI [0.94–2.32], P = 0.09). However, after adjustment with the age, sex, and body mass index, we observed significant association between NOS -786C allele and HTN status (OR = 2.08; 95%CI [1.18–3.66], P = 0.01).ConclusionOur results indicate that the C allele of the NOS3 gene is associated with increased risk of essential hypertension in this sample of the Algerian population of the Oran city. Further validation in larger samples is needed to confirm this finding.     

Seroprevalence of toxoplasmosis in pregnant women of the Marrakech-Safi region,Morocco

BackgroundToxoplasmosis is a parasitic infection caused by an intracellular protozoan named Toxoplasma gondii. Its prevalence had been investigated in several studies throughout the world showing that it varied from one country to another. In contrast, few studies had been carried out on this infection across the kingdom of Morocco, hence the objective of this work, which is the determination of Toxoplasma gondii seroprevalence in the region of Marrakech-Safi.MethodsThe serological results of a cohort of 5692 patients were reviewed retrospectively. Those patients had been into different public and private medical laboratories in the region of Marrakech-Safi for a toxoplasmosis serology, requested between the 1^st January, 2014 and 31^st December, 2016. According to each laboratory, the techniques adopted for this serology were ELISA (ELFA, MEIA, EIA) and CMIA.ResultsThe results showed that for pregnant women, the overall seroprevalence in the study region were 28.88%.ConclusionThe variation of Toxoplasma gondii seroprevalence is related not only to climatic factors but also to lifestyle, eating habits, socio-economic status and hygiene conditions. In this study, we noticed that in Morocco, as in other countries, pregnant women encounter several difficulties when serologic screening for toxoplasmosis.     

Overcoming Barriers to Parkinson Disease Trial Participation: Increasing Diversity and Novel Designs for Recruitment and Retention

Parkinson disease (PD) is highly prevalent among neurodegenerative diseases, affecting a diverse patient population. Despite a general willingness of patients to participate in clinical trials, only a subset of patients enroll in them. Understanding the barriers to trial participation will help to alleviate this discrepancy and improve trial participation. Underrepresented minorities, older patients, and patients with more medical comorbidities in particular are underrepresented in research. In clinical trials, this has the effect of delaying trial completion, exacerbating disparities, and limiting our ability to generalize study results. Efforts to improve trial design and recruitment are necessary to ensure study enrollment reflects the diversity of patients with PD. At the trial design level, broadening inclusion criteria, attending to participant burden, and focusing on trial efficiency may help. At the recruitment stage, increasing awareness, with traditional outreach or digital approaches; improving engagement, particularly with community physicians; and developing targeted recruitment efforts can also help improve enrollment of underrepresented patient groups. The use of technology, for virtual visits, technology-based objective measures, and community engagement, can also reduce participant burden and increase recruitment. By designing trials to consider these barriers to trial participation, we can improve not only the access to research for all our patients but also the quality and generalizability of clinical research in PD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-020-00960-0.     

Huge right ventricular mass revealing a testicular nonseminomatous germ cell tumor

Background

Cardiac intracavitary metastases from a testicular cancer are very unusual, and intra-cardiac metastasis is exceptionally the first expression of a noncardiac primary neoplasm. We report a case of a young patient for whom a cardiac symptom led to the diagnosis of a metastatic testicular cancer.

Enhancing the in vitro and in vivo activity of itraconazole against breast cancer using miltefosine-modified lipid nanocapsules

Itraconazole (ITC), a well-tolerated antifungal drug, exerts multiple anticancer effects which justified its preclinical and clinical investigation as potential anti-cancer agent with reduced side effects. Enhancement of ITC anti-cancer efficacy would bring valuable benefits to patients. We propose herein lipid nanocapsules (LNCs) modified with a subtherapeutic dose of miltefosine (MFS) as a membrane bioactive amphiphilic additive (M-ITC-LNC) for the development of an ITC nanoformulation with enhanced anticancer activity compared with ITC solution (ITC-sol) and unmodified ITC-LNC. Both LNC formulations showed a relatively small size (43–46 nm) and high entrapment efficiency (>97%), though ITC release was more sustained by M-ITC-LNC. Cytotoxicity studies revealed significantly greater anticancer activity and selectivity of M-ITC-LNC for MCF-7 breast cancer cells compared with ITC-sol and ITC-LNC. This trend was substantiated by in vivo findings following a 14 day-treatment of murine mammary pad Ehrlich tumors. M-ITC-LNC showed the greatest enhancement of the ITC-induced tumor growth inhibition, proliferation, and necrosis. At the molecular level, the tumor content of Gli 1, caspase-3, and vascular endothelial growth factor verified superiority of M-ITC-LNC in enhancing the ITC antiangiogenic, apoptotic, and Hedgehog pathway inhibitory effects. Finally, histopathological and biochemical analysis indicated greater reduction of ITC systemic toxicity by M-ITC-LNC. Superior performance of M-ITC-LNC was attributed to the effect of MFS on the structural and release properties of LNC coupled with its distinct bioactivities. In conclusion, MFS-modified LNC provides a simple nanoplatform integrating the potentials of LNC and MFS for enhancing the chemotherapeutic efficacy of ITC and possibly other oncology drugs.     

Distribution and metabolism of O-Ethyl O-4-nitrophenyl phenylphosphonothioate after a single oral dose in one-week old chicks

The toxicokinetics and metabolism of a single 1 mg (2.7 Ci/kg) oral dose of uniformly phenyl-labeled [¹⁴C]EPN (O-ethyl O-4-nitrophenyl [¹⁴C]phenylphosphonothioate) have been studied in 1-week old chicks. One control and three treated chicks were killed at each of the following time intervals: 0.5, 2, 4, 8, and 12 days. Radioactivity was rapidly absorbed from the gastrointestinal tract and distributed in all tissues. ¹⁴C in tissues reached a peak of 16.9% of the dose after 0.5 day and decreased to 0.6% at 4 days. The tissues of the gastrointestinal tract had the highest concentration of radioactivity, followed by bile and liver. Among nervous tissues, concentration of ¹⁴C was highest in the peripheral nerves. The spinal cord had the next highest concentration, while the brain had the least. After 4 days 91.3% of the ¹⁴C had been eliminated in the combined urinary-fecal excreta. By the end of the 12-day experiment this percentage reached 93.1%. No ¹⁴C was detected in the expired CO₂. Following the oral administration of [14C]EPN, a monophasic body level curve was observed. The half-life for the elimination of ¹⁴C from chick body was 16 h, corresponding to a rate constant of 0.04 h^–1. Most of the excreted ¹⁴C materials were identified as O-ethyl phenylphosphonic acid, phenylphosphonic acid, and O-ethyl phenylphosphonothioic acid.