Influcencia de los polimorfismos de ciclooxigenasa-2 en el desarrollo del adenocarcinoma gástrico en Aragón

Introducción: La Ciclooxigenasa 2 (Cox-2) es una enzima que interviene en la conversión del ácido araquidónico a prostaglandinas las cuales son importantes mediadores de la respuesta inmune a nivel gastrointestinal. La expresión de Cox-2 es inducida por agentes mitógenos y proinflamatorios y participa de forma directa en el proceso de carcinogénesis gástrica. Recientemente, se ha descrito la asociación de ciertos polimorfismos del gen PTGS2 (o COX- 2) con un mayor riesgo de desarrollar cáncer gástrico (CG). Puesto que la producción de Cox- 2 está regulada genéticamente, el objetivo de nuestro estudio fue analizar el papel de ciertos polimorfismos localizados en el gen PTGS2 en el desarrollo del CG en Aragón. Métodos: ADN genómico procedente de 240 pacientes con CG primario diagnosticados en 4 hospitales aragoneses y 240 individuos sanos emparejados por sexo y edad (± 5 años) fue tipado mediante técnicas de PCR, RFLP y TaqMan para el estudio de 5 SNPs localizados en el gen PTGS2 (-1195 G>A rs689466, -765 G>C rs20417, 3050 G>C rs5277, +8473 T>C rs5275 y +9850 A>G rs4648298). El estatus de infección por H. pylori y de anticuerpos frente a las citotoxinas CagA/VacA se realizó mediante Western blot. Resultados: El análisis de regresión logística identificó la infección por cepas CagA+ de H. pylori (OR: 2.79; 95% IC: 1.87-4.17, pC rs5275 se asoció con un mayor riesgo de CG (OR: 2.36; 95% IC: 1.19-4.68, modelo recesivo), principalmente de predominio distal (OR: 2.33; 95% IC: 1.13-4.80) y tipo histológico intestinal (OR: 2.76; 95% IC: 1.26-6.03). El análisis estratificado en función del estatus de infección por H. pylori, mostró que la asociación entre el SNP rs5275 y CG era estadísticamente significativa sólo en el subgrupo de individuos infectados por H. pylori (OR: 2.40; 95% IC:1.04-5.54; p= 0.03). Conclusión: Nuestros resultados sugieren que el polimorfismo +8473 T>C rs5275 del gen PTGS2 está implicado en la susceptibilidad al desarrollo del CG en la población aragonesa

Analysis of the information about Doctoral Degrees presented in the Spanish universities websites.

Globalization has intensified competition, as evidenced by the growing number of international classification systems (rankings) and the attention paid to them. Doctoral education has an international character in itself. It should promote opportunities for graduate students lo participate in these international studies. The quality and competitiveness are two of the most important issues for universities. To promote the interest of graduates to continue their education after the graduate level, it would be necessary to improve the published information of ihe doctoral programs. It should increase the visibility and provide high-quality, easily accessible and comparable information which includes all the relevant aspects of these programs. The authors analysed the website contents of doctoral programs, it was observed a lack of quality of them and very poor information about the contents, so that it was decided that any of them could constitute a model for creating new websites. The recommendations on the format and contents in the web were made by a discussion group. They recommended an attractive design; a page with easy access to contents and easy to find on Ihe net and with the information in more than one language. It should include complete program and academic staff information. It should also be included the study's results which should be easily accessible and includes quantitative data, such as number of students who completed scholars, publications, research projects, average duration of the studies, etc. It will facilitate the choice of progra

Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis

Objectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. Results: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. Conclusions: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE

Epidemiologic Features and Control Measures during Monkeypox Outbreak, Spain, June 2022

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.S

Cloxacillin or fosfomycin plus daptomycin combinations are more active than cloxacillin monotherapy or combined with gentamicin against MSSA in a rabbit model of experimental endocarditis

Background: In vitro and in vivo activity of daptomycin alone or plus either cloxacillin or fosfomycin compared with cloxacillin alone and cloxacillin plus gentamicin were evaluated in a rabbit model of MSSA experimental endocarditis (EE). Methods: Five MSSA strains were used in the in vitro time-kill studies at standard (105-106 cfu/mL) and high (108 cfu/mL) inocula. In the in vivo EE model, the following antibiotic combinations were evaluated: cloxacillin (2 g/4 h) alone or combined with gentamicin (1 mg/kg/8 h) or daptomycin (6 mg/kg once daily); and daptomycin (6 mg/kg/day) alone or combined with fosfomycin (2 g/6 h). Results: At standard and high inocula, daptomycin plus fosfomycin or cloxacillin were bactericidal against 4/5 and 5/5 strains, respectively, while cloxacillin plus gentamicin was bactericidal against 3/5 strains at standard inocula but against none at high inocula. Fosfomycin, cloxacillin, gentamicin and daptomycin MIC/MBCs of the MSSA-678 strain used in the EE model were: 8/64, 0.25/0.5, 0.25/0.5 and 1/8 mg/L, respectively. Adding gentamicin to cloxacillin significantly reduced bacterial density in vegetations compared with cloxacillin monotherapy (P = 0.026). Adding fosfomycin or cloxacillin to daptomycin [10/11 (93%) and 8/11 (73%), respectively] significantly improved the efficacy of daptomycin in sterilizing vegetations [0/11 (0%), P < 0.001 for both combinations] and showed better activity than cloxacillin alone [0/10 (0%), P < 0.001 for both combinations] and cloxacillin plus gentamicin [3/10 (30%), P = 0.086 for cloxacillin plus daptomycin and P = 0.008 for fosfomycin plus daptomycin]. No recovered isolates showed increased daptomycin MIC. Conclusions: The addition of cloxacillin or fosfomycin to daptomycin is synergistic and rapidly bactericidal, showing better activity than cloxacillin plus gentamicin for treating MSSA EE, supporting their clinical use

Diagnostic yield of chest and thumb ECG after cryptogenic stroke, Transient ECG Assessment in Stroke Evaluation (TEASE): an observational trial

Objective In stroke survivors, atrial fibrillation (AF) is typically evaluated solely by short-term ECG monitoring in the stroke unit. Prolonged continuous ECG monitoring or insertable cardiac monitors require substantial resources. Chest and thumb ECG could provide an alternative means of AF detection, which in turn could allow prompt anticoagulation to prevent recurrent stroke. The objective of this study was to assess the yield of newly diagnosed AF during 28 days of chest and thumb ECG monitoring two times per day in cryptogenic stroke.Methods This study, Transient ECG Assessment in Stroke Evaluation, included patients who had a stroke from Region Gävleborg, Sweden, between 2017 and 2019. Patients with a recent ischaemic stroke without documented AF (or other reasons for anticoagulation) before or during ECG evaluation in the stroke unit were evaluated using the Coala Heart Monitor connected to a smartphone application for remote monitoring.Results The prespecified number of 100 patients (mean age 67.6±10.8 years; 60% men) was analysed. In nine patients (9%, number needed to screen 11) AF but no other significant atrial arrhythmias (&gt;30 s) was diagnosed. The mean CHA2DS2-VASc score was similar among patients with AF and no AF (4.9±1.1 vs 4.3±1.3; p=0.224) and patients with AF were older (74.3±9.0 vs 66.9±10.8; p=0.049). Patients performed on average 90.1%±15.0% of scheduled transmissions.Conclusion In evaluation of cryptogenic stroke, 9% of patients had AF detected using chest and thumb ECG two times per day during 1 month. In many stroke survivors, this is a feasible approach and they will be potentially protected from recurrent stroke by anticoagulation treatment.Trial registration number NCT03301662

Prevalence and genotype distribution of cervical human papilomavirus infection in the pre-vaccination era: a population-based study in the Canary Islands

Objective National Spanish studies show that prevalence of cervical human papillomavirus (HPV) infection in the female population is increasingly frequent, with an overall estimate of 14% in women aged 18–65 years. The objective of this study is to know the prevalence and distribution of HPV types in the female population of the Canary Islands prior to the introduction of HPV vaccines and to investigate the associated clinical and sociodemographic factors.Methods Based on the Primary Health Care database, a sample of adult women (aged 18–65 years) of Gran Canaria (GC) and Tenerife (TF) stratified into nine age groups was carried out between 2002 and 2007. Women were contacted by postal letter and telephone call and were visited in their primary care centre. A clinical-epidemiological survey was completed and cervical samples were taken for cytological study and HPV detection. HPV prevalence and its 95% CI were estimated, and multivariate analyses were performed using logistic regression to identify factors associated with the infection.Results 6010 women participated in the study, 3847 from GC and 2163 from TF. The overall prevalence of HPV infection was 13.6% (CI 12.8%–14.5%) and 11.1% (CI 10.3%–11.9%) for high-risk types. The most frequent HPV type was 16 followed by types 51, 53, 31, 42 and 59. HPV types included in the nonavalent vaccine were detected in 54.1% of infected women. Factors associated with an increased risk of infection were: young ages (18–29 years), the number of sexual partners throughout life, not being married, being a smoker, and having had previous cervical lesions or genital warts.Conclusions It is confirmed that prevalence of HPV infection in the female population of the Canary Islands is high, but similar to that of Spain, HPV 16 being the most frequent genotype. The determinants of infection are consistent with those of other populations

Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT1R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.</p