Polyphasic molecular approach to the characterization of methanogens in the saliva of Tunisian adults.

OBJECTIVES: Methanogenic archaea are a minor component of human oral microbiota. Due to their relatively low abundance, the detection of these neglected microorganisms is challenging. This study concerns the presence of methanogens in salivary samples collected from Tunisian adults to evaluate their prevalence and burden using a polyphasic molecular approach. METHODS: A total of 43 saliva samples were included. Metagenomic and standard 16S rRNA sequencing were performed as an initial screening to detect the presence of methanogens in the oral microbiota of Tunisian adults. Further investigations were performed using specific quantitative real-time PCR targeting Methanobrevibacter oralis and Methanobrevibacter smithii. RESULTS: Methanobrevibacter was detected in 5/43 (11.62 %) saliva samples after metagenomic 16S rRNA data analysis. The presence of M. oralis was confirmed in 6/43 samples by standard 16S rRNA sequencing. Using real-time PCR, methanogens were detected in 35/43 (81.39 %) samples, including 62.79 % positive for M. oralis and 76.74 % positive for M. smithii. These findings reflect the high prevalence of both methanogens, revealed by the high sensitivity of the real-time PCR approach. Interestingly, we also noted a significant statistical association between the detection of M. smithii and poor adherence to a Mediterranean diet, indicating the impact of diet on M. smithii prevalence. CONCLUSION: Our study showed the presence of methanogens in the oral microbiota of Tunisian adults with an unprecedented relatively high prevalence. Choice of methodology is also central to picturing the real prevalence and diversity of such minor taxa in the oral microbiota.

Oxidative stress markers-driven prognostic model to predict post-discharge mortality in heart failure with reduced ejection fraction.

Background: Current predictive models based on biomarkers reflective of different pathways of heart failure with reduced ejection fraction (HFrEF) pathogenesis constitute a useful tool for predicting death risk among HFrEF patients. The purpose of the study was to develop a new predictive model for post-discharge mortality risk among HFrEF patients, based on a combination of clinical patients' characteristics, N-terminal pro-B-type Natriuretic peptide (NT-proBNP) and oxidative stress markers as a potentially valuable tool for routine clinical practice. Methods: 116 patients with stable HFrEF were recruited in a prospective single-center study. Plasma levels of NT-proBNP and oxidative stress markers [superoxide dismutase (SOD), glutathione peroxidase (GPX), uric acid (UA), total bilirubin (TB), gamma-glutamyl transferase (GGT) and total antioxidant capacity (TAC)] were measured in the stable predischarge condition. Generalized linear model (GLM), random forest and extreme gradient boosting models were developed to predict post-discharge mortality risk using clinical and laboratory data. Through comprehensive evaluation, the most performant model was selected. Results: During a median follow-up of 525 days (7-930), 33 (28%) patients died. Among the three created models, the GLM presented the best performance for post-discharge death prediction in HFrEF. The predictors included in the GLM model were age, female sex, beta blockers, NT-proBNP, left ventricular ejection fraction (LVEF), TAC levels, admission systolic blood pressure (SBP), angiotensin-converting enzyme inhibitors/angiotensin receptor II blockers (ACEI/ARBs) and UA levels. Our model had a good discriminatory power for post-discharge mortality [The area under the curve (AUC) = 74.5%]. Based on the retained model, an online calculator was developed to allow the identification of patients with heightened post-discharge death risk. Conclusion: In conclusion, we created a new and simple tool that may allow the identification of patients at heightened post-discharge mortality risk and could assist the treatment decision-making.

A potential oral microbiome signature associated with coronary artery disease in Tunisia.

The coronary artery disease (CAD) is a chronic inflammatory disease involving genetic as well as environmental factors. Recent evidence suggests that the oral microbiome has a significant role in triggering atherosclerosis. The present study assessed the oral microbiome composition variation between coronary patients and healthy subjects in order to identify a potential pathogenic signature associated with CAD. We performed metagenomic profiling of salivary microbiomes by 16S ribosomal RNA (rRNA) next-generation sequencing. Oral microbiota profiling was performed for 30 individuals including 20 patients with CAD and ten healthy individuals without carotid plaques or previous stroke or myocardial infarction. We found that oral microbial communities in patients and healthy controls are represented by similar global core oral microbiome. The predominant taxa belonged to Firmicutes (genus Streptococcus, Veillonella, Granulicatella, Selenomonas), Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus Rothia), Bacteroidetes (genus Prevotella, Porphyromonas), and Fusobacteria (genus Fusobacterium, Leptotrichia). More than 60% relative abundance of each sample for both CAD patients and controls is represented by three major genera including Streptococcus (24.97 and 26.33%), Veillonella (21.43 and 19.91%), and Neisseria (14.23 and 15.33%). Using penalized regression analysis, the bacterial genus Eikenella was involved as the major discriminant genus for both status and Syntax score of CAD. We also reported a significant negative correlation between Syntax score and Eikenella abundance in coronary patients' group (Spearman rho = -0.68, P=0.00094). In conclusion, the abundance of Eikenella in oral coronary patient samples compared with controls could be a prominent pathological indicator for the development of CAD.

Design and Rationale of the National Tunisian Registry of Heart Failure (NATURE-HF): Protocol for a Multicenter Registry Study.

BACKGROUND: The frequency of heart failure (HF) in Tunisia is on the rise and has now become a public health concern. This is mainly due to an aging Tunisian population (Tunisia has one of the oldest populations in Africa as well as the highest life expectancy in the continent) and an increase in coronary artery disease and hypertension. However, no extensive data are available on demographic characteristics, prognosis, and quality of care of patients with HF in Tunisia (nor in North Africa). OBJECTIVE: The aim of this study was to analyze, follow, and evaluate patients with HF in a large nation-wide multicenter trial. METHODS: A total of 1700 patients with HF diagnosed by the investigator will be included in the National Tunisian Registry of Heart Failure study (NATURE-HF). Patients must visit the cardiology clinic 1, 3, and 12 months after study inclusion. This follow-up is provided by the investigator. All data are collected via the DACIMA Clinical Suite web interface. RESULTS: At the end of the study, we will note the occurrence of cardiovascular death (sudden death, coronary artery disease, refractory HF, stroke), death from any cause (cardiovascular and noncardiovascular), and the occurrence of a rehospitalization episode for an HF relapse during the follow-up period. Based on these data, we will evaluate the demographic characteristics of the study patients, the characteristics of pathological antecedents, and symptomatic and clinical features of HF. In addition, we will report the paraclinical examination findings such as the laboratory standard parameters and brain natriuretic peptides, electrocardiogram or 24-hour Holter monitoring, echocardiography, and coronarography. We will also provide a description of the therapeutic environment and therapeutic changes that occur during the 1-year follow-up of patients, adverse events following medical treatment and intervention during the 3- and 12-month follow-up, the evaluation of left ventricular ejection fraction during the 3- and 12-month follow-up, the overall rate of rehospitalization over the 1-year follow-up for an HF relapse, and the rate of rehospitalization during the first 3 months after inclusion into the study. CONCLUSIONS: The NATURE-HF study will fill a significant gap in the dynamic landscape of HF care and research. It will provide unique and necessary data on the management and outcomes of patients with HF. This study will yield the largest contemporary longitudinal cohort of patients with HF in Tunisia. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262675; https://clinicaltrials.gov/ct2/show/NCT03262675. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12262.

Heart failure disease: An African perspective.

Heart failure remains a health challenge in Africa, associated with significant rates of hospitalization, morbidity and mortality. The current review aims to summarize the most recent data on the epidemiology, aetiology, risk factors and management of heart failure, comparing countries in North Africa and sub-Saharan Africa. There is a paucity of data on heart failure epidemiology, aetiology and management, and on the sociodemographic characteristics of African patients with heart failure. Heart failure prevalence has been evaluated among all medical admissions or admissions to cardiac units or emergency departments in a few hospital-based studies conducted in countries in North Africa and sub-Saharan Africa. Common causes of heart failure in Africa include ischaemic heart disease, hypertensive heart disease, dilated cardiomyopathy and valvular heart disease. The aetiology of heart failure differs between countries in North Africa and sub-Saharan Africa. Diagnosing heart failure proves challenging in Africa because of a lack of basic tools and the necessary human resources. The principal drugs used frequently for heart failure therapy are lacking in sub-Saharan Africa. The clinical profile of heart failure in sub-Saharan Africa differs from that in North African countries; this is related to aetiological factors, socioeconomic status and availability of diagnostic tools. There is an evident need to establish a large multicentre registry to evaluate the heart failure burden in almost all African countries, and to highlight the major cardiovascular risk factors and co-morbidities. The present review highlights the importance of this syndrome in Africa, and calls for improvements in its early diagnosis, treatment and, possibly, prevention.

Non-classical human leukocyte antigen class I in Tunisian children with autism.

Autism spectrum disorders (ASD) are one of the most common childhood morbidities characterized by deficits in communication and social skills. Increasing evidence has suggested associations between immune genes located in the human leukocyte antigen (HLA) complex and etiology of autism. In this study, we investigated whether the non-classical class I HLA-G, -E, and -F polymorphisms are associated with genetic predisposition to autism in Tunisia. We aimed to find a correlation between HLA-G genotypes and soluble HLA-G (sHLA-G) levels. We have analyzed the HLA-G, -E, and -F genotypes of 15 autistic children and their parents. DNA typing of HLA class I genes was performed using PCR-SSP and PCR-RFLP methods. Also, we evaluated the serum levels of HLA-G (1 and 5) by a validated ELISA technique in autistic probands and their parents. No association was found between any polymorphism and autism in the study subjects. Additionally, we found no correlation between sHLA-G1 and sHLA-G5 and autism. Also, no significant difference in sHLA-G testing in parents and offspring was found. However, parents carrying [GG] genotype presented a higher sHLA-G levels than those carrying ([CC]+[GC]) genotypes (p = 0.037). From this preliminary study, we conclude that the investigated polymorphisms of HLA-G, -E, and -F genes did not lead to autism susceptibility in Tunisian children. However, the CGTIGA haplotype was found to be associated with the disease.