Highly conserved gsc1 gene of Pneumocystis jirovecii in patients with or without prior exposure to Echinocandins

International audienceEchinocandins are noncompetitive inhibitors of the GSC1 subunit of the enzymatic complex involved in synthesis of 1,3-beta-D-glucan, a cell wall component of most fungi, including Pneumocystis spp. Echinocandins are widely used for treating systemic candidiasis and rarely used for treating Pneumocystis pneumonia. Consequently, data on P. jirovecii gsc1 gene diversity are still scarce, compared to the homologous fks1 gene of Candida spp. In this study, we analyzed P. jirovecii gsc1 gene diversity and the putative selection pressure of echinocandins on P. jirovecii. Gsc1 gene sequences of P. jirovecii specimens from two patient groups were compared. One group of 27 patients had prior exposure to echinocandins whereas the second group of 24 patients did not, at the time of P. jirovecii infection diagnoses. Two portions of P. jirovecii gsc1 gene, HS1 and HS2, homologous to hot spots described in Candida spp., were sequenced. Three SNPs at positions 2204, 2243, and 2303 close to the HS1 region and another SNP at position 4540 more distant from the HS2 region were identified. These SNPs represent synonymous mutations. Three gsc1 HS1 alleles, A, B, and C, and two gsc1 HS2 alleles, a and b, and four haplotypes, Ca, Cb, Aa, and Ba, were defined, without significant difference in haplotype distribution in both patient groups ( p = 0.57). Considering the identical diversity of P. jirovecii gsc1 gene and the detection of synonymous mutations in both patient groups, no selection pressure of echinocandins among P. jirovecii microorganisms can be pointed out so far

Smoking Effect on Ischemic Heart Disease in Young Patients

Objective: To evaluate the effect of tobacco smoking on the risk of nonfatal acute myocardial infarction in young adults (≤45 years). Patient and Methods: We conducted a population-based case-control study with 329 incident acute myocardial infarction cases (42 women; 287 men), consecutively admitted to the Cardiology department of hospitals in Aleppo, Syria, and 778 controls (486 women; 292 men), selected within the noninstitutionalized Aleppo population, during 2008-2010. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using unconditional logistic regression. Results: The prevalence of current smoking was 80.8% in male cases and 53.8% in male controls (OR = 3.63, 95%CI: 2.50, 5.27) and 59.5% of female cases were smokers compared with 35.8% of controls (OR = 2.64, 95%CI: 1.39, 5.02). No interaction was found between current smoking and gender on myocardial infarction risk (P = 0.401). A dose-effect response was present, the odds favoring myocardial infarction reaching an eight-fold increase for those who smoked >25 cigarettes/day compared with never smokers. The risk estimate for former smokers was similar to never smokers. Conclusions: Tobacco smoking is an important independent risk factor for acute myocardial infarction in young adults, with similar strength of association for both genders