R46L polymorphism in the PCSK9 gene: Relationship to lipid levels, subclinical vascular disease, and erectile dysfunction.

BACKGROUND: The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. OBJECTIVE: To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). METHODS: We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population. In 473 male participants, we also investigated its relationship with ED. The association of the R46L polymorphism with lipid levels was also assessed in 2 cohorts of 1103 prepuberal children and 830 adolescents. RESULTS: The prevalence of the T allele was 2.9% in adults. Low-density lipoprotein cholesterol (LDL-cholesterol) levels did not vary according to this polymorphism (134 ± 32 vs 134 ± 31 mg/dL, for the TT + GT vs GG carriers, respectively, P = .931). Despite equal LDL-cholesterol levels, adults carrying the T allele had a lower mean common carotid IMT (0.685 ± 0.09 vs 0.723 ± 0.127 mm; P = .035), a lower maximum common carotid IMT (0.819 ± 0.11 vs 0.865 ± 0.159 mm; P = .040), and, in males, a lower prevalence of ED (36.8% vs 61%: P = .036), than GG carriers. Prevalence of the T allele was 3.2% in both cohorts of children. They had lower levels of LDL-cholesterol than GG subjects (100 vs 109 mg/dL; P = .060, for prepuberal children, and 85 vs 99 mg/dL; P = .010 for adolescents). CONCLUSION: In our population, an association between the PCSK9 R46L variant and LDL-cholesterol levels is observed in children. In adults, although its association with lipid levels is not evident, there is a significant relationship between the PCSK9 R46L variant and markers of subclinical atherosclerosis, including IMT and ED.

Relationship of the Adherence to a Mediterranean Diet and Its Main Components with CRP Levels in the Spanish Population.

Background: Adherence to a Mediterranean diet seems to be inversely associated with C-reactive protein (CRP) concentration. A 14-point Mediterranean Diet Adherence Screener (MEDAS) has been developed to assess dietary compliance. Objective: The aim of this study was to assess whether each of the MEDAS questions as well as their final score were associated with the levels of CRP in general Spanish population. METHODS: Cross-sectional analysis of 1411 subjects (mean age 61 years, 43.0% males) randomly selected from the general population. CRP levels were determined by a commercial ELISA kit. Adherence to the Mediterranean diet was measured by the 14-point MEDAS. Results: There was an inverse correlation between adherence to the Mediterranean diet and the CRP concentration, even after adjusting by age, gender, hypertension, metabolic syndrome, body mass index, statin treatment and hypertension treatment (p = 0.041). Subjects who consume ≥2 servings of vegetables per day (p = 0.003), ≥3 pieces of fruit per day (p = 0.003), ≥1 serving of butter, margarine, or cream per day (p = 0.041) or ≥3 servings of fish/seafood per week (p = 0.058) had significantly lower levels of CRP. Conclusions: Adherence to a Mediterranean-type diet measured by a simple questionnaire is associated with lower CRP concentration. However, this association seems to be particularly related to a higher consumption of vegetables, fruits, dairy products, and fish.

Interhospital spread of NDM-7-producing Klebsiella pneumoniae belonging to ST437 in Spain.

This study describes an interhospital spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) producing NDM-7 carbapenemase that started in December 2013 in Madrid, Spain. NDM-7-producing CRKP were isolated from urine, rectal swabs or blood samples from seven patients admitted to three different hospitals (Hospital Universitario La Paz, Hospital de Cantoblanco and Hospital Central de la Cruz Roja). The isolates were resistant to all antimicrobials tested except colistin and fosfomycin. One blood isolate was susceptible to minocycline and tigecycline but was resistant to fosfomycin. All isolates were closely related by pulsed-field gel electrophoresis (PFGE) and DiversiLab(®) analysis and belonged to multilocus sequence typing (MLST) sequence type 437. In addition, blaNDM-7, blaTEM-1, blaCTX-M-15 and aac(3)-IIa were identified. Family contacts of the index case were negative for NDM-producing bacteria. The outbreak occurred in two separate waves and the cases associated with Hospital de Cantoblanco had been admitted to the same room. Environmental samples from the trap of a sink and a shower in this room were positive for NDM-7-producing CRKP. To our knowledge, this is the first reported worldwide outbreak of NDM-7-producing CRKP. No relationship with the Indian continent, the Balkans or the Middle East could be established. Frequent transfer of aged or chronically ill patients between the facilities involved may have favoured the spread of NDM-7-producing CRKP. The spread of the second wave in Hospital de Cantoblanco probably occurred as a result of transmission from an environmental reservoir.

Anisakis allergy component-resolved diagnosis: clinical and immunologic differences between patients from Italy and Spain.

BACKGROUND: Anisakissimplex is the main organism responsible for the zoonotic disease anisakiasis which follows the ingestion of live larvae present in raw or undercooked marine fish. Clinical features include severe epigastric pain, frequently accompanied by severe allergic reactions. We investigated the prevalence of immunoglobulin E (IgE) specific for 5 Anisakis allergens in Italian patients sensitized or allergic to the parasite. The results were compared with those obtained previously in a similar Spanish population. PATIENTS AND METHODS: We conducted a descriptive, cross-sectional validation study. Asymptomatic Anisakis-sensitized subjects (15 Italian and 17 Spanish) and Anisakis allergic-patients (42 Italian and 35 Spanish) were studied by ImmunoCAP, Western-blotting with nAni s 4 and dot-blotting with rAni s 1, rAni s 5, rAni s 9 and rAni s 10. RESULTS: Anisakis IgE CAP classes 1 or 2 were associated with a high probability of asymptomatic sensitization (66.7%) while CAP classes 4 or above, were associated with a very high probability of allergy to Anisakis (95.2%). The most frequently detected allergen among Italian and Spanish allergic patients was Ani s 1. All of the Spanish patients versus 76.2% of the Italian patients recognized at least one of the allergens tested. Patients suffering from gastrointestinal symptoms only were significantly more frequent among the Italians whereas the Spanish presented more frequently with urticaria, angioedema or anaphylaxis. CONCLUSIONS: Anisakis hypersensitivity shows different immunological patterns in different European countries. Allergen component diagnosis might help us to better understand this complex entity. Anisakis-specific IgE levels may have moderate prognostic significance.

Anisakis simplex recombinant allergens increase diagnosis specificity preserving high sensitivity.

BACKGROUND: So far, the frequency of Anisakis simplex-specific IgE antibodies has been determined by skin prick tests (SPTs) and the ImmunoCAP system. These commercial methods have good sensitivity, but their specificity is poor because they use complete parasite extracts. Our aim was to determine the frequency of sensitization to A. simplex using recombinant Ani s 1, Ani s 3, Ani s 5, Ani s 9 and Ani s 10 and to evaluate these allergens for diagnosis, comparing their performance with the commercial methods. PATIENTS AND METHODS: We conducted a descriptive, cross-sectional validation study performed in an allergy outpatient hospital clinic. Patients without fish-related allergy (tolerant patients, n = 99), and A. simplex-allergic patients (n = 35) were studied by SPTs, ImmunoCAP assays and detection of specific IgE to A. simplex recombinant allergens by dot blotting. RESULTS: SPTs and ImmunoCAP assays were positive in 18 and 17% of tolerant patients, respectively. All A. simplex-allergic patients had positive SPTs and ImmunoCAP assays. Specific IgE against at least one of the A. simplex recombinant allergens tested was detected in 15% of sera from tolerant patients and in 100% of sera from A. simplex-allergic patients. Detection of at least one A. simplex recombinant allergen by dot blotting and ImmunoCAP assay using complete extract showed a diagnostic sensitivity of 100% with both methods. However, the specificity of dot blotting with A. simplex recombinant allergens was higher compared with ImmunoCAP (84.85 vs. 82.83%). CONCLUSIONS: There are 15% of tolerant patients with specific IgE against important A. simplex allergens. The recombinant allergens studied here increase the specificity of A. simplex diagnosis while keeping the highest sensitivity. A. simplex recombinant allergens should be included with A. simplex allergy diagnostic tests to improve their specificity.