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Background: Vitamin D deficiency is one of the most common medical conditions worldwide. In Tunisia, several studies evaluated Vitamin D status, but this was concerning specific populations (pregnant women, obese or diabetic patients and children with asthma). The only study that evaluated Vitamin D status in a healthy Tunisian population was conducted by Meddeb and associeties in 2002. The update of data available, based on the currently recommended limits, is necessary. This study aimed to estimate the prevalence of hypovitaminosis D in a healthy Tunisian population, and correlate the values with potential risk factors. Methods: It was conducted on 209 Tunisian healthy subjects. Data collected included clinical characteristics and dietary intakes. We measured 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), glycemia, creatinine, calcium, phosphorus, and alkaline phosphatase concentrations. Hypovitaminosis D was retained for 25(OH)D concentrations

Background: Zinc (Zn) deficiency is a common condition and could contribute to poor outcomes in hemodialysis (HD) patients. The aim of this study was to evaluate the effects of Zn supplementation on serum copper (Cu) to Zn and C-reactive protein (CRP) to albumin ratios (CAR) in HD patients. Methods: Seventy-seven HD patients were enrolled in a multicentre simple-blind randomized clinical trial. Only 37 HD patients completed the study; they were randomly divided into two groups and supplemented with zinc sulphate (n=17) or placebo (n=20) for two months. Serum Zn and Cu were measured by atomic absorption spectrophotometry. Serum albumin and hypersensitive-CRP were assessed by colorimetric and immunoturbidimetric method, respectively. Determinations were performed before and after supplementation. Results: After two months of supplementation, serum Zn significantly increased, and Cu to Zn ratio decreased in Zn supplemented group, but remained unchanged in the placebo group. In parallel, serum albumin concentrations significantly increased, and CAR decreased in Zn supplemented group only. Conclusions: Zn supplementation reduces Cu to Zn and CRP to albumin ratios in HD patients. These changes point towards an improvement in nutritional, oxidative and inflammatory status. The study findings suggest that correcting Zn deficiency reduces poor outcomes in HD patients.

Background: Chronic kidney disease (CKD) is associated with numerous complications such as bone mineral disorder. The aim of our study was to analyze the correlation of bone turnover markers with Bone Mineral Density (BMD) measurements in Tunisian end stage renal diseases (ESRD) patients. Methods: This study included 100 ESRD Tunisian patients. Their estimated glomerular filtration rate (eGFR) was < 15 mL X min-1 X (1.73 m2)-1, which requires hemodialysis. Bone-specific alkaline phosphatase (BALP) serum concentration was determined with a chemiluminescence immunoassay. Fibroblast Growth Factor 23 (FGF23) serum was assessed by Enzyme-Linked Immunosorbent Assay method. The serum levels of 25-Hydroxyvitamin D (25(O H)D), intact parathyroid hormone (iPTH) and Beta cross-laps (CTX) was measured by Electrochemiluminescence Technology. DEXA (dual-energy x-ray absorptiometry) technique was used to evaluate BMD. Results: We observed a statistically significant negative correlation between BALP levels and total body BMD (r =-0.268; P = 0.015) particularly in femoral neck (FN) (r = - 0.219; P = 0.037). BALP concentrations were negatively associated with total BMD especially in FN for patients with BMI < 30, FGF23 concentrations were also negatively correlated with BMD in lumbar spine site (LS) (r = -0.209; P = 0.046). For osteopenic patients we found an inverse correlation between 25(OH)D concentrations and BMD in LS position (r = -0.336; P = 0.038). In men group, we have also found a negative correlation between iPTH and total BMD (r = -0.326; P = 0.015). However we found a positive correlation between calcium expression and BMD in LS site (r = 0.270; P = 0.031). Conclusions: FGF23 and BALP can predict bone loss in ESRD through their strong correlation with BMD in LS and FN sites respectively.

Abstract Diabetes and hypertension are a serious public health problem worldwide. In the last decades, prevalence of these two metabolic diseases has dramatically increased in the Middle East and North Africa region, especially in Tunisia. This study aimed to determine the prevalence of type 2 diabetes (T2D) and High Blood Pressure (HBP) in Zaghouan, a North-East region of Tunisia. To this end, an exploratory study with stratified random sampling of 420 participants has been carried out. Various data were collected. Blood samples and urine were drawn for biochemical assay. Then, all data were analyzed using the statistical R software. Results showed an alarming situation with an inter-regional difference in prevalence of obesity (50.0%, CI 95.0%), HBP (39.0%, CI 95.0%) and T2D (32.0%, CI 95.0%). This study allowed the discovery of 24, 17 and 2 new cases of T2D, HBP and T2D&HBP respectively. The association of some socio-economic factors and biochemical parameters with these chronic diseases has been highlighted. To conclude, the health situation in the governorate of Zaghouan requires urgent interventions to better manage the growing epidemic of non-communicable diseases (NCD) in the region. This study demonstrated the importance of engaging health policy makers in road mapping and implementing national NCD prevention programs.

IntroductionType 2 diabetes (T2D) is a multifactorial disease involving genetic and environmental components. Several genome-wide association studies (GWAS) have been conducted to decipher potential genetic aberrations promoting the onset of this metabolic disorder. These GWAS have identified over 400 associated variants, mostly in the intronic or intergenic regions. Recently, a growing number of exome genotyping or exome sequencing experiments have identified coding variants associated with T2D. Such studies were mainly conducted in European populations, and the few candidate-gene replication studies in North African populations revealed inconsistent results. In the present study, we aimed to discover the coding genetic etiology of T2D in the Tunisian population.MethodsWe carried out a pilot Exome Wide Association Study (EWAS) on 50 Tunisian individuals. Single variant analysis was performed as implemented in PLINK on potentially deleterious coding variants. Subsequently, we applied gene-based and gene-set analyses using MAGMA software to identify genes and pathways associated with T2D. Potential signals were further replicated in an existing large in-silico dataset, involving up to 177116 European individuals.ResultsOur analysis revealed, for the first time, promising associations between T2D and variations in MYORG gene, implicated in the skeletal muscle fiber development. Gene-set analysis identified two candidate pathways having nominal associations with T2D in our study samples, namely the positive regulation of neuron apoptotic process and the regulation of mucus secretion. These two pathways are implicated in the neurogenerative alterations and in the inflammatory mechanisms of metabolic diseases. In addition, replication analysis revealed nominal associations of the regulation of beta-cell development and the regulation of peptidase activity pathways with T2D, both in the Tunisian subjects and in the European in-silico dataset.ConclusionsThe present study is the first EWAS to investigate the impact of single genetic variants and their aggregate effects on T2D risk in Africa. The promising disease markers, revealed by our pilot EWAS, will promote the understanding of the T2D pathophysiology in North Africa as well as the discovery of potential treatments.

Introduction: Monogenic diabetes (MD) accounts for 3%–6% of all cases of diabetes. This prevalence is underestimated due to its overlapping clinical features with type 1 and type 2 diabetes. Hence, genetic testing is the most appropriate tool for obtaining an accurate diagnosis. In Tunisia, few cohorts of MD have been investigated until now. The aim of this study is to search for pathogenic variants among 11 patients suspected of having MD in Tunisia using whole-exome sequencing (WES).Materials and methods: WES was performed in 11 diabetic patients recruited from a collaborating medical center. The pathogenicity of genetic variation was assessed using combined filtering and bioinformatics prediction tools. The online ORVAL tool was used to predict the likelihood of combinations of pathogenic variations. Then, Sanger sequencing was carried out to confirm likely pathogenic predicted variants among patients and to check for familial segregation. Finally, for some variants, we performed structural modeling to study their impact on protein function.Results: We identified novel variants related to MD in Tunisia. Pathogenic variants are located in several MODY and non-MODY genes. We highlighted the presence of syndromic forms of diabetes, including the Bardet–Biedl syndrome, Alström syndrome, and severe insulin resistance, as well as the presence of isolated diabetes with significantly reduced penetrance for Wolfram syndrome-related features. Idiopathic type 1 diabetes was also identified in one patient.Conclusion: In this study, we emphasized the importance of genetic screening for MD in patients with a familial history of diabetes, mainly among admixed and under-represented populations living in low- and middle-income countries. An accurate diagnosis with molecular investigation of MD may improve the therapeutic choice for better management of patients and their families. Additional research and rigorous investigations are required to better understand the physiopathological mechanisms of MD and implement efficient therapies that take into account genomic context and other related factors.

C17-sphinganine analog mycotoxin (C17-SAMT) has been characterized as the contaminant responsible for the atypical toxicity reported in mussels from the Bizerte lagoon (northern Tunisia) over the past decade. C17-SAMT exhibited common symptoms of toxicity in mice, including flaccid paralysis and severe respiratory distress, followed by rapid death. To determine the potential health risks of this neurotoxin, we assessed its subchronic toxicity according to the recommendations of OCDE n° 407. The body weight and the structural changes of vital organs were recorded. Biochemical and hematological parameters were also quantified. Macroscopic observations showed that mice treated with 0.9, 9, and 90 µg/kg C17-SAMT had significantly reduced stomach weights, swollen and fragile intestines, and signs of nephritis with renal abscesses. Transaminase assays pointed out that exposure to C17-SAMT can lead to transaminitis. Above-average lactate dehydrogenase values were recorded in both the treated and satellite groups. Hematology data showed a significant reduction in red blood cell counts in high-dose-treated group. Reductions in hemoglobin and hematocrit were also recorded. Mean leukocyte counts were significantly elevated in the high-, mid-dose treated and satellite groups. At the microscopic level, we noted myocardial atrophy and hyperemia. In the lungs, we noted necrosis associated with macrophages perivascular infiltration and congestion. The kidneys showed mild inflammation and glomerular atrophy. The stomach exhibited mucosal atrophy, while a thin colon and distended small intestine were observed in high-dose-treated group. The liver was affected by vascular congestion, inflammatory infiltration, and lobular necrosis that evolved into acute hepatitis. Lesions, such as inflammatory infiltration and mild necrosis of the liver, cortical abscess with central necrosis in the kidney, and mild congestion of cardiac tissue were recorded in the satellite group.

Purpose – This paper aims to investigate the link between agency costs mitigation via three levels of rights protection (minority rights protection, enforcing contracts, resolving insolvency issues) provides the propitious climate for financing investment opportunities around the world. Design/methodology/approach – We use Bartlett’s three-group method to stratify countries based on how well they protect investors as measured by the scores provided in the Doing Business dataset developed by the world bank for 189 countries. We then test a variety of independent hypotheses that the alleviation of agency costs via three levels of protection (minority investors’ rights, contract enforcement, resolving insolvency issues) is associated with better access to credit via the banking system, better valuation of listed firms via the stock market and higher investment and growth. Findings – Our findings support Agency Theory which explains why the absence of legal protection of external investors leads to stock markets and financial institutions failing to fulfill their role of financing the economy. Practical implications – The policy implication from this study indicates that countries ought to (1) develop legislation that protects investors’ rights, (2) improve the quality of their judicial system in terms of enforcing the legislation and (3) build the framework for resolving disputes during insolvency as these are important ingredients for a developed financial system. Originality/value – We use the World bank dataset and a new methodology to quantify the significance of the relationship between minority rights protection, ineffective enforcement, lack of bankruptcy laws and access to firm financing via the banking sector and the stock market. It provides new evidence that the quality of the judicial system in a country matter for firms’ ability to raise financing and enhance value creation. 研究目的 – 本文旨在探討一個假設，該假設為透過三級別權利保障（保障少數群體的權利、執行合同、解決破產問題）的代理成本緩減會為世界各地的金融性投資機會提供良好的氣侯。 研究設計/方法/理念 – 我們以巴特利特（Bartlett）的三組法把國家分組，分組方法是基於該國家保障投資者的程度，而保障程度是以世界銀行為189個國家而制定的營商資料集內提供的評分來衡量的。我們把國家分組後，便就各樣的獨立假設進行測試。這些假設是：透過三級別保障（保障少數股權投資者的權利、合同的執行、解決破產問題）的代理成本緩減是連繫於透過銀行系統而產生的更佳信貸途徑，透過股市的更佳上市公司估值及更高的投資和增長。 研究結果 – 研究結果証實了代理理論，該理論說明為何當外來投資者沒有得到法律保障時，結果會導致股票市場和金融機構不能履行其為經濟提供資金的角色。 實際的意義 – 本研究具有政策方面的意義，因研究顯示了國家應該：（1）設立保障投資者權利的法律；（2）在執行法律方面，改善其司法系統的素質；（3）建立解決破產時爭議的體系。這些是應該做的，因它們是一個已發展的金融體制的重要元素。 研究的原創性/價值 – 本文強調了一個保障投資者權利的法律環境所需的三個特定要素：對少數股權投資者權利的保障、有效的執行、有效的破產法律及透過銀行部門和股票市場而取得公司融資。這提供新的證據, 證實這三級別權利保障對公司籌集資金及提高價值創造的能力而言至為重要。

The prevalence of Type 2 diabetes (T2D) is increasing worldwide. Genetics and lifestyle, especially diet, are contributing factors. Analyses of macro- and micronutrient intake across global populations may help to explain their impact on glucose homeostasis and disease development. To this end, 420 Tunisians were enrolled in a prospective cross-sectional study of daily food consumption. Various data were collected and blood samples were drawn for biochemical assay. A 24-h recall questionnaire was obtained from participants to evaluate dietary intake. Statistical analyses were conducted using Nutrilog and R software. Biochemical analyses stratified the studied population (n = 371) into three groups: diabetics (n = 106), prediabetics (n = 192) and controls (n = 73); 49 subjects were excluded. Our results showed that Tunisians had hypercaloric diets high in carbohydrates and fat with variability in the levels of some vitamins and minerals, including riboflavin and niacin, that were statistically different among groups. The lower intake of vitamin D was associated with a greater risk of T2D. Higher vitamin A and sodium intake were associated with poor glucose homeostasis, although protein intake may improve it. In perspective, nutrigenomic studies can provide insight into problematic diets and poor eating habits and offer opportunities to analyze the effects of behavioral changes that can mitigate T2D development and progression.

The authors recently developed a damage identification method which combines ambient vibration measurements and a Statistical Modal Filtering approach to predict the location and degree of damage. The method was then validated experimentally via ambient vibration tests conducted on full-scale reinforced concrete laboratory specimens. The main purpose of this paper is to demonstrate the feasibility of the identification method for a real bridge. An important challenge in this case is to overcome the absence of vibration measurements for the structure in its undamaged state which corresponds ideally to the reference state of the structure. The damage identification method is, therefore, modified to adapt it to the present situation where the intact state was not subjected to measurements. An additional refinement of the method consists of using a genetic algorithm to improve the computational efficiency of the damage localization method. This is particularly suited for a real case study where the number of damage parameters becomes significant. The damage diagnosis predictions suggest that the diagnosed bridge is damaged in four elements among a total of 168 elements with degrees of damage varying from 6% to 18%.