Trends and risk factors of hepatitis A in Catalonia after the introduction of a hepatitis A+B vaccination programme.

At the end of 1998, universal hepatitis A+B vaccination of 12 year olds was introduced in Catalonia. The aim was to examine trends in hepatitis A during 2005-2015 and assess risk factors by age group. We carried out an observational epidemiological study of the incidence and risk factors of hepatitis A reported to the surveillance system. Information on exposure was recorded for each case for the 2-6 weeks before symptom onset. Spearman's coefficient was used to evaluate the trends of rates. The chi-square test was used to compare categorical. We studied 2621 hepatitis A cases; the age mean was 26.6 years (SD=18.2), and >50% of cases were in the 20-49 years age group. The incidence decreased from 3.28/100 000 in 2005 to 1.50/100 000 in 2015. The rate for women decreased over time (P = .008), but the reduction was not significant in men (P = .234). Men consistently had higher rates than women with the biggest difference being in the 20-34 years age group (rate 8.8 vs 2.8). The greatest risk factor was travel to an endemic country (42.1%) in the 0-19 years age group and male-to-male sexual contact (18.6%) in the 20-49 years age group. The case fatality rate in adults aged >49 years was 0.4%. In conclusion, the vaccination programme of preadolescents resulted in a reduction in hepatitis A cases. However, a significant amount of cases still appear in immigrants and men who have sex with men. Hepatitis A in adults is an emerging health problem that will require new strategies.

Identification of a founder EPCAM deletion in Spanish Lynch syndrome families.

Germline deletions at the 3'-end of EPCAM have been involved in the etiology of Lynch syndrome (LS). The aim of this study was to characterize at the molecular level Spanish families harboring EPCAM deletions. Non-commercial multiplex ligation-dependent probe amplification (MLPA) probes and long-range polymerase chain reaction (PCR) amplification were used to characterize each deletion. Haplotyping was performed by analyzing eight microsatellite markers and five MSH2single nucleotide polymorphisms (SNPs). Methylation of MSH2 was analyzed by methylation specific-MLPA. Tumors diagnosed in seven Spanish families harboring EPCAM deletions were almost exclusively colorectal. Mosaicism in MSH2 methylation was observed in EPCAM deletion carrier samples, being average methylation levels higher in normal colon and colorectal tumors (27.6% and 31.1%), than in lymphocytes and oral mucosa (1.1% and 0.7%). Three families shared the deletion c.858 + 2568_*4596del, with a common haplotype comprising 9.9 Mb. In two families the novel EPCAM deletion c.858 + 2488_*7469del was identified. This study provides knowledge on the clinical and molecular characteristics of mosaic MSH2 epimutations. The identification of an EPCAM founder mutation has useful implications for the molecular diagnosis of LS in Spain.

Detection of novel genetic variation in autosomal dominant retinitis pigmentosa.

We explored an approach to detect disease-causing sequence variants in 448 candidate genes from five index cases of autosomal dominant retinitis pigmentosa (adRP) by sequence DNA capture and next-generation DNA sequencing (NGS). Detection of sequence variants was carried out by sequence capture NimbleGen and NGS in a SOLiD platform. After filtering out variants previously reported in genomic databases, novel potential adRP-causing variants were validated by dideoxy capillary electrophoresis (Sanger) sequencing and co-segregation in the families. A total of 55 novel sequence variants in the coding or splicing regions of adRP candidate genes were detected, 49 of which were confirmed by Sanger sequencing. Segregation of these variants in the corresponding adRP families showed three variants present in all the RP-affected members of the family. A novel mutation, p.L270R in IMPDH1, was found to be disease causing in one family. In another family a variant, p.M96T in the NRL gene was detected; this variant was previously reported as probably causing adRP. However, the previously reported p.A76V mutation in NRL as a cause of RP was excluded by co-segregation in the family. We discuss the benefits and limitations of our approach in the context of mutation detection in adRP patients.

Novel p.M96T variant of NRL and shRNA-based suppression and replacement of NRL mutants associated with autosomal dominant retinitis pigmentosa.

Mutations in the gene encoding the transcription factor neural retina leucine zipper (NRL) are known to cause autosomal dominant (adRP) or recessive (arRP) retinitis pigmentosa (RP). In an adRP Spanish family, we detected a novel sequence variation (c.287T>C) in the NRL gene that results in the p.M96T protein change. A functional test of the ability of NRL, in conjunction with cone-rod homeobox (CRX), to transactivate a human rhodopsin (RHO) promoter was used to evaluate the pathogenic mechanisms of NRL. We found upregulation of the RHO promoter by p.M96T protein similar to that shown by other missense NRL mutations that cause adRP. Affected RP patients of the family carry the nucleotide change, although two other family members that also carry the c.287T>C variation remain asymptomatic. This result complicates the genetic counselling of the family. The pathogenic mechanisms associated with adRP NRL mutations appear to be caused by a gain of function. To suppress the negative effect of an NRL mutant, the suppression and replacement strategy seems to be the most suitable therapeutic approach capable of overcoming the mutational heterogeneity associated with NRL-linked adRP. Thus, we evaluated this methodology in the NRL gene for the first time.

Measles antibodies and response to vaccination in children aged less than 14 months: implications for age of vaccination.

Passive immunity against measles decreases during the first months of life. The objective of this study was to determine titres of measles antibodies in children aged 9-14 months and their mothers before vaccination, and the children's response to vaccination. Blood samples were collected by capillary puncture before and 28 days after vaccination. Samples were obtained between February and June 2007 during an ongoing measles outbreak. Titres of specific measles IgG antibodies were determined by enzyme-linked immunosorbent assay. Seroconversion was defined as the presence of antibodies after vaccination in subjects without antibodies before vaccination. Maternal antibodies were present in 37·7% of all 69 children included and in 45·1% of children aged 9 months. Of the 51 children in whom a second sample was obtained, 31 (60·8%) were seronegative before vaccination and 61·3% seroconverted. Interference of maternal antibodies was 30%. Advancing the first dose of measles vaccination from 15 to 12 months is a correct strategy, given the increase in the time of susceptibility of infants to measles.

Interlaboratory validation of a hanging pendulum thrust balance for electric propulsion testing.

A hanging pendulum thrust balance has been developed by Imperial College London in collaboration with the European Space Agency (ESA) to characterize a wide range of static fire electric propulsion and chemical micro-propulsion devices with thrust in the range of 1 mN to 1 N. The thrusters under investigation are mounted on a pendulum platform, which is suspended from the support structure using stainless steel flexures. The displacement of the platform is measured using an optical laser triangulation sensor. Thermal stability is ensured by a closed loop self-compensating heating system. The traceability and stability of the calibration are ensured using two separate calibration subsystems: a voice coil actuator and a servomotor pulley system. Two nearly identical thrust balances have been constructed, with one being tested in the Imperial Plasma Propulsion Laboratory and the other in the ESA Propulsion Laboratory. Both balances show a high degree of linearity in the range of 0.5 mN-100 mN. Both instruments have demonstrated a stable calibration over several days, with an estimated standard deviation on thrust measurements better than 0.27 mN for low thrust measurements. The same electric propulsion test article was used during both tests: a Quad Confinement Thruster (QCT) variant called QCT Phoenix. This thruster differed from previous QCT designs by having a newly optimized magnetic topology. The device produced thrust up to 2.21 ± 0.22 mN with a maximum specific impulse of 274 ± 41 s for an anode power range of 50 W-115 W.

The influence of public or private paediatric health care on vaccination coverages in children in Catalonia (Spain).

BACKGROUND: Maintaining high vaccination coverages is necessary in order to control vaccine-preventable diseases. We studied vaccination coverages in a representative sample of 630 children aged <3 years in Catalonia in order to determine the relationship between vaccination coverages and socioeconomic factors. METHODS: Sampling was carried out in a representative sample of the health regions in Catalonia stratified according to habitat. A sample of 630 parents of children aged <3 years born in October 2001 were interviewed by telephone. Information collected included sociodemographic data, type of health care provider (public or private) and information on vaccination coverage for the basic plus booster immunization series (BBI) which consisted of: four DTP, four OPV, one MMR and the doses of Hib and MenC necessary according to age of administration of the first dose. RESULTS: A total of 87.62% of the children were vaccinated with the BBI series, and no statistically significant differences in coverage between public (87.93%) and private (88.30%) paediatric providers, or between social classes (high: 87.58%, low: 88.81%) were found. Vaccination coverage was associated with attending a day-care centre (OR: 1.89; 95% CI: 1.12-3.21) and maternal university education (OR: 1.84; 95% CI: 1.01-3.33). CONCLUSION: Vaccination coverages are high and are similar between types of provider, probably due to preventive policies which have made a concerted effort to ensure universal vaccination.

Impact of primary NO2 emissions at different urban sites exceeding the European NO2 standard limit.

A large part of the European population is still exposed to ambient nitrogen dioxide (NO2) levels exceeding the European Union (EU) air quality standards, being a key challenge to reduce NO2 concentrations across many European urban areas, particularly close to roads. In this work, a trend analysis of pollutants involved in NO2 processes was done for the period 2003-2014 in traffic sites from three Spanish cities (Barcelona, Madrid and Granada) that still exceed the European NO2 air quality standard limits. We also estimated the contributions of primary NO2 emissions and photo-chemically formed NO2 to the observed ambient NO2 concentrations in order to explore their possible role in the observed NO2 concentration trends. The NOx and NO concentrations at these traffic sites showed significant decreasing trends during the period 2003-2014, especially at Barcelona (BARTR) and Madrid (MADTR) traffic stations. The NO2 concentrations showed statistically significant downward trends at BARTR and MADTR and remained unchanged at Granada traffic station (GRATR) during the study period. Despite the significant decrease in NO2 concentrations in BCNTR and MADTR during the analysed period, the NO2 concentrations observed over these sites still above the annual NO2 standard limit of 40 µg m-3 and, therefore, more efficient measures are still needed. Primary NO2 emissions significantly influence NO2 concentrations at the three analysed sites. However, as no drastic changes are expected in the after-exhaust treatment technology that can reduce primary NO2 emissions to zero in the near future, only a substantial reduction in NOx emissions will help to comply with the NO2 European air quality standards. Reduction of 78%, 56% and 16% on NOx emissions in Barcelona, Madrid and Granada were estimated to be necessary to comply with the NO2 annual limit of 40 µg m-3.

Epidemiology of hepatitis A before and after the introduction of a universal vaccination programme in Catalonia, Spain.

A universal vaccination program for preadolescents, aged 12 years, with the hepatitis A + B vaccine was introduced in 1998 in Catalonia (Spain) with the aim of protecting the whole population against hepatitis A. The hepatitis A + B vaccine program replaced the hepatitis B vaccination program for preadolescent started in 1991. The impact of the hepatitis A + B vaccination program was studied by assessment of the trend of reported cases of hepatitis A. All cases of viral hepatitis reported from 1992 to 2006 were included in the study. To evaluate changes in the epidemiology of hepatitis A, two periods were considered: a prevaccination period (1992-1998) and a post-vaccination period (2001-2006). The ratios of the rates were calculated according to age and sex. The comparison of rates and proportions was made by calculation of the normal z statistic. A total of 7536 cases of viral hepatitis were reported, of which 4109 (54.52%) were hepatitis A. The incidence rate of hepatitis A fell from 5.44 per 100 000 person-years in the prevaccination period to 3.02 in the post-vaccination period. In males, the rate fell from 6.85 to 3.89 and in females from 4.10 to 2.18. The male-female ratio of incidence rates was lower in the post-vaccination period. In males the global decline of incidence rate was 43.26% and in females 46.96%. The greatest decline occurred in the 15 to 19 years age group in both sexes (79.1% in men and 78.34% in women) but declines in the 10-14 years age group were also very important (69.21% and 67.88%, respectively). In conclusion, hepatitis A incidence fell in Catalonia in the post-vaccination period in vaccinated adolescents and also in other unvaccinated groups who have benefited from the indirect effects of the vaccination program.

[Maturity onset diabetes of the young (MODY)]. / Diabetes MODY. Una causa frecuente de hiperglucemia.

Hyperglycemia is an increasing cause of consultation in Paediatrics. Diagnosis depends on the context. Under the name of diabetes numerous clinical entities are included. MODY (maturity onset diabetes of the young) is, after type 1 diabetes, the most frequent cause of diabetes in childhood. For its diagnosis, a high degree of suspicion is needed and we have to be aware of the family history.

Trifluralin: photolysis under sunlight conditions and reaction with HO* radicals.

The gas phase atmospheric degradation of trifluralin (a widely used herbicide) has been investigated at the EUPHORE facility. Its photolysis has been studied under sunlight conditions and its reaction rate constant with HO() radicals was measured using the relative rate method. Using 1,3,5-trimethylbenzene as reference compound, the rate constant of HO() reaction with trifluralin was obtained to be [formula: see text] The mean photolysis rate measured under solar radiation was [formula: see text] . The photolysis of trifluralin was found to generate organic aerosols with a yield of (20 +/-10)%. The data obtained enabled us to discuss the atmospheric fate of trifluralin in the gas phase.

Serological survey of hepatitis B immunity in healthcare workers in Catalonia (Spain).

Healthcare workers (HCW) are exposed to preventable infectious diseases, notably hepatitis B (HB). The aim of this study was to determine the immunity of HCW against hepatitis B. We made a seroprevalence study using a self-administered survey and obtained blood samples. Antibodies against the HB surface antigen (anti-HBs) and against the HB core antigen (anti-HBc) were studied. The odds ratio (OR) and 95% confidence intervals (CI) were calculated. The adjusted OR were calculated using logistic regression. Of the 644 HCW who participated (29.7% physicians, 38.7% nurses, 13.4% other clinical workers and 18.3% non-clinical workers), 46.4% were primary care workers and 53.6% hospital workers. The overall prevalence of anti-HBs was 64.4%. HCW aged <25 y had a significantly higher prevalence (86.7%) than those aged 35-44 y (adjusted OR 3.40; 95% CI 1.06-10.90). The prevalence of anti-HBc was 4.1%, and increased with age. Significant differences were found for HCW aged >44 y with respect to those aged 25-34 y. 75.6% of HCW stated they were vaccinated, but only 39.3% had a vaccination card. In HCW who stated they were unvaccinated, 10.8% had a vaccinated serological pattern (anti-HBc-negative and anti-HBs -positive). Written, updated vaccination records are essential to reliably determine the vaccination status.

[Prevalence and risk factors for early postoperative infection after liver transplantation]. / Prevalencia y factores de riesgo asociados a la infección en el postoperatorio inmediato del trasplante hepático.

OBJECTIVES: To analyze factors related to the development of infection soon after a liver transplant. PATIENTS AND METHOD: Retrospective study of 1000 liver transplants in adults between 1991 and 2004. Pre-, intra- and postoperative variables of recipients were analyzed in 2 groups according to whether infection did or did not develop. RESULTS: Infection developed in 151 patients. Bacterial infections were the most common type. Significant risk factors for infection in the multivariate analysis were sex (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.33-0.90); Child-Pugh stage (OR, 1.89; 95% CI, 1.29-2,77); hepatitis C virus cirrhosis (OR, 0.58; 95% CI, 0.34-0.99); post-reperfusion syndrome (OR, 1.82; 95% CI, 1.03-3.21); vena cava preservation technique (OR, 0.43; 95% CI, 0.22-0.84); history of diabetes mellitus (OR, 2.38; 95% CI, 1.34-4.22); respiratory distress syndrome (OR, 6.60; 95% CI, 1.16-37.45); pulmonary edema (OR, 2.36; 95% CI, 1.44-3.86); renal dysfunction (OR, 3.25; 95% CI, 1.89-5.60); acute renal insufficiency (OR, 20.24; 95% CI, 9.88-41.46); neurological alterations (OR, 3.36; 95% CI, 1.94-5.821); postoperative bleeding (OR, 2.80; 95% CI, 1.32-5.97); graft dysfunction (OR, 2.07; 95% CI, 1.21-3.53); primary graft failure (OR, 0.07; 95% CI, 0.01-0.33). CONCLUSION: Infection is a serious complication that continues to be difficult to control. Certain risk factors can be improved with careful management (kidney failure, pulmonary edema) or appropriate donor-recipient matching (initial dysfunction). Others, however, are inherent to the procedure (post-reperfusion syndrome, sex) or to immunosuppression, which acts as a true mediator of infection with regard to both its appearance and its clinical manifestation.

Two novel frameshift mutations in BRCA2 gene detected by next generation sequencing in a survey of Spanish patients of breast cancer.

PURPOSE: To analyze BRCA1 and BRCA2 genes using a cost-effective and rapid approach based on next generation sequencing (NGS) technology. METHODS: A population of Spanish cancer patients with a personal or familial history of breast and/or ovarian cancer was analyzed for germline mutations in BRCA1 and BRCA2 genes. The methodology relies on a 5 multiplex PCR assay coupled to NGS. RESULTS: Ten pathogenic mutations (four in BRCA1 and six in BRCA2 gene) were identified in a Spanish population. The deletion c.1792delA, in exon 10, and the duplication c.5869dupA, in exon 11 of BRCA2 gene were not previously reported and should be considered as pathogenic due to its frameshift nature. CONCLUSION: Two novel frameshift mutations in BRCA2 gene were detected using the multiplex PCR-based assay following by NGS.

Vitamin A deficiency causes oxidative damage to liver mitochondria in rats.

Mitochondrial damage in rat liver induced by chronic vitamin A-deficiency was studied using three different groups of rats: (i) control rats, (ii) rats fed a vitamin A-free diet until 50 d after birth and (iii) vitamin A-deficient rats re-fed a control diet for 30 d. No statistical difference in body weight and food intake was found between control and vitamin A-deficient rats. Liver GSH concentration was similar in both groups. However, in vitamin A-deficient rats, the mitochondrial GSH/GSSG ratio was significantly lower and the levels of malondialdehyde (MDA) and 8-oxo-7, 8-dihydro-2'-deoxyguanosine (oxo8dG) were higher when compared to control rats. These values were partially restored in re-fed rats. The mitochondrial membrane potential of vitamin A-deficient rats was significantly lower than in control rats and returned to normal levels in restored vitamin A rats. Two populations of mitochondria were found in vitamin A-deficient rats according to the composition of membrane lipids. One population showed a similar pattern to the control mitochondria and the second population had a higher membrane lipid content. This report emphasizes the protective role of vitamin A in liver mitochondria under physiological circumstances.

Na+ dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) in primary astrocyte cultures: effect of oxidative stress.

The Na+ -dependent L-glutamate transporters EAAT1(GLAST), EAAT2 (GLT-1) and EAAT3 (EAAC1) are expressed in primary astrocyte cultures, showing that the EAAT3 transporter is not neuron-specific. The presence of these three transporters was evaluated by RT-PCR, immunoblotting, immunocytochemical techniques, and transport activity. When primary astrocyte cultures were incubated with L-buthionine-(S,R)-sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase, the GSH concentration was significantly lower than in control cultures, but the expression and amount of protein of EAAT1, EAAT2 and EAAT3 and transport of L-glutamate was unchanged. Oxidative stress was created by adding H(2)O(2) or tert.-butyl hydroperoxide (t-bOOH) to the primary astrocyte cultures and cell damage was evaluated by measuring activity of lactate dehydrogenase. Under oxidative stress, GSH levels were significantly lower than in control astrocytes; but the expression and the amount of protein of the three transporters remained unchanged. However, L-glutamate uptake was significantly lower in astrocytes under oxidative conditions when compared to controls. L-Glutamate uptake was not changed in the presence of ascorbate, but was partially recovered in the presence of DTT and GSH ethyl ester. This report emphasizes that oxidative stress and not GSH depletion alters transporter activity without changing transporter expression.

[Neonatal tumors]. / Tumores neonatales.

We review the cases of congenital and neonatal tumors treated at the Children's Hospital La Fe, Valencia. A total of 25 cases of neonatal benign tumors and 27 cases of malignant tumors were diagnosed. The most frequent benign tumor was solid teratoma (12 cases). The most frequent malignant tumor was neuroblastoma (14 cases). Variations in histology, clinical evolution and therapy in relation to age are described. The results obtained are compared with those previously published.

[Evolution of conservative treatment in traumatic spleen injuries. Report of 54 cases]. / Evolución en el tratamiento conservador de las lesiones esplénicas traumáticas: presentación de 54 casos.

The spleen is the organ most frequently affected in abdominal trauma. Conservative treatment of traumatic spleen injuries is already generally accepted, avoiding surgery whenever possible. We present a wide serie (54 cases) of traumatic spleen injuries along a period of ten years (1990-2000) during which 83% of these were solved with conservative therapy we analyse our treatment procedure and post-treatment follow-up of these patients.

[Surgical treatment of pediatric pulmonary metastases]. / Tratamiento quirúrgico de las metástasis pulmonares pediátricas.

OBJECTIVE: We comment and update the surgical treatment for pulmonary metastases (PM) within a multidisciplinary approach for paediatric cancer. MATERIAL AND METHODS: We analyse patients with PM who have been operated between 1976-1996. Scientific literature published in the last 25 years (Cancerlit and Medline) was reviewed. RESULTS: PM from 13 patients were removed. Seven were males and 6 females with a mean age 5 4/12 years (range: 11 months- 12 3/12 years). Diagnoses were Wilms' tumour (7), osteosarcoma (3), Ewing sarcoma (1), rabdomiosarcoma (1), Yolk sac tumour (1). PM were unilateral in 7 cases and bilateral in six cases. PM appeared synchronically in four patients and metacronically in nine cases (3 of these after chemotherapy). All patients received chemotherapy and four of them local radiotherapy. Surgery consisted on radical segmentectomy and only one patient needed lobectomy due to a local relapse. Nowadays five patients (38%) are in complete remission with a mean follow-up from surgery of 11 11/12 years (range: 6 3/12-20 years). CONCLUSIONS: Metastasectomy is an important surgical technique in global treatment of children with PM and for a selected group of patients it can offer the only opportunity for curation.