Apolipoprotein E polymorphism in the Tunisian population: frequency and effect on lipid parameters

OBJECTIVES: We determined the frequencies of apolipoprotein E (apo E) gene alleles and examined the association between apo E polymorphism and lipid parameters in a sample of the Tunisian population. DESIGN AND METHODS: Apo E polymorphism was investigated using PCR, and plasma lipid parameters were measured in 122 men and 111 women aged 35 to 87 years. RESULTS: The allele frequencies were epsilon2: 7.3%, epsilon3: 84.6%, and epsilon4: 8.1%. Apo E polymorphism was associated with significant differences (P<0.001) in total cholesterol, apo B and LDL cholesterol in both men and women. epsilon2 carriers had the lowest mean total cholesterol, apo B and LDL-C concentrations, and subjects with the epsilon4 allele had the highest levels. Triglycerides levels increased with the epsilon4 allele, but this did not reach statistical significance. These results remained unchanged after adjustment for age, body mass index, sex, hypertension, diabetes and smoking. However, in obese subjects (BMI>30 kg/m2), TG concentrations were significantly lower in individuals homozygous for the epsilon3 allele compared to those with the alleles epsilon2 or epsilon4. CONCLUSION: In this sample of the Tunisian population, the distribution of apo E gene alleles is similar to that observed in Southern European populations with low prevalence of the epsilon4 allele. Variations in the apo E gene play a role in determining plasma lipid levels. These data also suggest that effects of apo E alleles on lipids levels are partly dependent on environmental variables such as BMI. These findings highlight the importance of the gene/environment interaction on the deleterious effect of obesity on cardiovascular risk factors.     

Regulation of growth factor receptor degradation by ADP-ribosylation factor domain protein (ARD) 1

ADP-ribosylation factor domain protein 1 (ARD1) is a 64-kDa protein containing a functional ADP-ribosylation factor (GTP hydrolase, GTPase), GTPase-activating protein, and E3 ubiquitin ligase domains. ARD1 activation by the guanine nucleotide-exchange factor cytohesin-1 was known. GTPase and E3 ligase activities of ARD1 suggest roles in protein transport and turnover. To explore this hypothesis, we used mouse embryo fibroblasts (MEFs) from ARD1-/- mice stably transfected with plasmids for inducible expression of wild-type ARD1 protein (KO-WT), or ARD1 protein with inactivating mutations in E3 ligase domain (KO-E3), or containing persistently active GTP-bound (KO-GTP), or inactive GDP-bound (KO-GDP) GTPase domains. Inhibition of proteasomal proteases in mifepristone-induced KO-WT, KO-GDP, or KO-GTP MEFs resulted in accumulation of these ARD1 proteins, whereas KO-E3 accumulated without inhibitors. All data were consistent with the conclusion that ARD1 regulates its own steady-state levels in cells by autoubiquitination. Based on reported growth factor receptor-cytohesin interactions, EGF receptor (EGFR) was investigated in induced MEFs. Amounts of cell-surface and total EGFR were higher in KO-GDP and lower in KO-GTP than in KO-WT MEFs, with levels in both mutants greater (p = 0.001) after proteasomal inhibition. Significant differences among MEF lines in content of TGF-β receptor III were similar to those in EGFR, albeit not as large. Differences in amounts of insulin receptor mirrored those in EGFR, but did not reach statistical significance. Overall, the capacity of ARD1 GTPase to cycle between active and inactive forms and its autoubiquitination both appear to be necessary for the appropriate turnover of EGFR and perhaps additional growth factor receptors.     

A Comparative Systematic Review of COVID-19 and Influenza

Background: Both SARS-CoV-2 and influenza virus share similarities such as clinical features and outcome, laboratory, and radiological findings. Methods: Literature search was done using PubMed to find MEDLINE indexed articles relevant to this study. As of 25 November 2020, the search has been conducted by combining the MeSH words “COVID-19” and “Influenza”. Results: Eighteen articles were finally selected in adult patients. Comorbidities such as cardiovascular diseases, diabetes, and obesity were significantly higher in COVID-19 patients, while pulmonary diseases and immunocompromised conditions were significantly more common in influenza patients. The incidence rates of fever, vomiting, ocular and otorhinolaryngological symptoms were found to be significantly higher in influenza patients when compared with COVID-19 patients. However, neurologic symptoms and diarrhea were statistically more frequent in COVID-19 patients. The level of white cell count and procalcitonin was significantly higher in influenza patients, whereas thrombopenia and elevated transaminases were significantly more common in COVID-19 patients. Ground-grass opacities, interlobular septal thickening, and a peripheral distribution were more common in COVID-19 patients than in influenza patients where consolidations and linear opacities were described instead. COVID-19 patients were significantly more often transferred to intensive care unit with a higher rate of mortality. Conclusions: This study estimated differences of COVID-19 and influenza patients which can help clinicians during the co-circulation of the two viruses.     

Fallacy of thoracic side-branch steal from the internal mammary artery: analysis of left internal mammary artery coronary flow during thoracic side-branch occlusion with pharmacologic and exercise-induced hyperemia.

In some patients, myocardial ischemia after coronary artery bypass graft surgery has been attributed to a coronary steal phenomenon through a thoracic side branch originating from the left internal mammary artery (LIMA), even in the absence of subclavian or LIMA stenosis. To demonstrate that coronary flow through the LIMA is unchanged by occlusion of a LIMA side branch, we examined LIMA coronary flow velocity measurements (0.014" Doppler flow wire) in three patients at rest, during adenosine hyperemia, and again during hyperemia induced by left arm exercise before and again after the balloon occlusion of the thoracic side branch. For the three patients, no significant changes in resting or hyperemic flow were noted due to side-branch occlusion. Before side-branch occlusion, pharmacologic intra-arterial (adenosine) coronary flow reserve (hyperemic-to-basal flow velocity ratio) was 2.6, 1.5, and 3.2 and exercise flow reserve was 2.1, 1.3, and 1.2, respectively. After side-branch occlusion, pharmacologic coronary flow reserve was 2.5, 1.8, and 2.7 with exercise flow reserve of 1.8, 1.1, and 1.3, respectively. Under most ordinary circumstances, thoracic side-branch steal does not exist and that side-branch occlusion does not alter LIMA flow at rest or during pharmacologic or exercise-induced hyperemia. These data further suggest that a demonstration of the physiologic value of side-branch occlusion should precede surgical or percutaneous interruption of the thoracic artery in such patients.     

Validation of the mini pediatric asthma quality of life questionnaire and identification of risk factors affecting quality of life among Lebanese children

Background: Few studies used various scales to assess the QOL in Lebanon in general but none was specific to asthma. Our objective was to assess the asthma-related quality of life, using the mini Pediatric Asthma Quality of Life Questionnaire (PAQLQ), in Lebanese asthmatic children, check its validity compared to the original version, and identify clinical and sociodemographic risk factors that might affect these children's QOL. Methods: This retrospective study included 300 children aged between 7–16 years (51.6% boys and 48.4% girls). To confirm the mini-PAQLQ questionnaire construct validity in the Lebanese population, an exploratory factor analysis was launched for the 13 items of the questionnaire, using the principal component analysis technique. Cronbach's alpha was recorded for reliability analysis. A multivariate analysis linear regression was carried out, taking the QOL score as the dependent variable. Results: The correlation coefficients for factors 1 (symptoms and emotions) and 2 (activities) were similar to that of the original scale. High Cronbach's alphas were found for factor 1 (0.914), factor 2 (0.888), and the full scale (0.921). Uncontrolled asthma, the child's respiratory problems before the age of 2 years, and the presence of pets at home significantly decreased the children's asthma-related quality of life (Beta = ?1.541; Beta = ?6.846, and Beta = ?5.364, respectively). Conclusion: We were able to validate the mini-PAQLQ among the Lebanese population. The identification of risk factors, some of which are amenable to intervention, especially uncontrolled asthma, could lead to an improvement in the asthmatic children's QOL.