Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

Different patterns of A*80:01:01:01 allele generation based on exon or intron sequences.

Generation of the HLA-A*80:01:01:01 allele has been analysed using its complete sequence. Direct comparison of the sequences and phylogenetic trees using the human leukocyte antigen (HLA)-A representative alleles and the major histocompatibility complex (MHC)-A sequences of non-human primates has been made. Results based on exon sequences confirm previously published, but considering only the sequences of the introns, two distinct regions can be differentiated. The first one comprises from the 5' untranslated region region to the first part of intron 3 sequence (shared with A2 family), and the second one includes the sequence from the end of intron 3 to intron 7 (shared with A1/A3/A11/A36/A30 family). Each of them clusters with Gorilla and Chimpanzee MHC-A sequences, respectively, suggesting an origin coming from a common ancestor to Gorilla and Chimpanzee.

Identification of the novel HLA-DQB1*03:03:02:04 allele in a Spanish individual.

HLA-DQB1*03:03:02:04 and DQB1*03:03:02:02 alleles differ by a single point mutation in intron 2.

Resilience and related factors in urban, mid-aged Spanish women.

OBJECTIVE: To assess resilience and related factors among urban, mid-aged Spanish women. METHODS: This was a cross-sectional study performed in 227 women aged 40-65 years who filled out the 14-item Wagnild and Young Resilience Scale (WYRS-14), the Menopause Rating Scale (MRS) and a questionnaire containing personal sociodemographic data. RESULTS: For the whole sample, median (interquartile range) age and total WYRS-14 score were 52.4 (8.7) years and 79 (20.0) points, respectively. Resilience score was inversely related to non-working status, non-university studies, depressed mood, perimenopausal status, and higher MRS total scores (≥ 17). Using the 25th percentile of the obtained total WYRS-14 score as a cut-off value to define lower resilience (< 68.0 points), logistic regression analysis determined that low resilience was related to being unemployed, having depressed mood and being perimenopausal. Drinking less than 3 units/day of alcohol was significantly related to higher resilience. CONCLUSION: In this sample of urban, mid-aged Spanish women, low resilience (lower WYRS-14 scores) was related to unemployment status, depressed mood and severe menopausal symptoms.

Predictive value of sequential models of uterine artery Doppler in pregnancies at high risk for pre-eclampsia.

OBJECTIVE: To evaluate the performance of models described previously for the prediction of pre-eclampsia (PE), based on the sequential evaluation of uterine artery resistance at 11-13 weeks and 19-22 weeks, in a high-risk population. METHODS: This was a prospective study in 135 women with singleton pregnancies and at least one of the following high-risk conditions: PE and/or intrauterine growth restriction in a previous pregnancy, chronic hypertension, pregestational diabetes, renal disease, body mass index > 30 kg/m(2) , autoimmune disease (systemic lupus erythematosus, antiphospholipid syndrome or rheumatoid arthritis) and thrombophilia. Mean uterine artery pulsatility index (mUtA-PI) at 11-13 and at 19-22 weeks' gestation was measured and analyzed according to quantitative and semi-quantitative models, to predict late PE (resulting in delivery ≥ 34 weeks) and early PE (delivery < 34 weeks). RESULTS: Late PE developed in 21 (15.6%) pregnancies and early PE in six (4.4%). Using mUtA-PI, the detection rates of late and early PE for a false-positive rate of 10% were 14.3% and 33.3%, respectively, at 11-13 weeks, and 19.0% and 66.7%, respectively, at 19-22 weeks. Using a semi-quantitative approach, the group of pregnant women with mUtA-PI ≥ 90(th) percentile at both 11-13 and 19-22 weeks had a greater risk for early PE (odds ratio, 21.4 (95% CI, 2.5-184.7)) compared with the group with mUtA-PI < 90(th) percentile at both periods. Using a quantitative approach, there was relative worsening in the mUtA-PI (multiples of the median) from the first to the second trimester in all cases of early PE. CONCLUSION: The application of semi-quantitative and especially quantitative models to evaluate sequential changes in uterine artery Doppler findings between the first and second trimesters could be of additional value in assessing high-risk women regarding their true risk of developing early PE.

The novel HLA-G*01:03:01:02 allele differs from G*01:03:01:01 by a possible inversion event in intron 3.

HLA-G*01:03:01:02 and G*01:03:01:01 differ by a two nucleotide changes in intron 3.

Neurobiological and psychopathological variables related to emotional instability: a study of their capability to discriminate patients with bulimia nervosa from healthy controls.

OBJECTIVE: To analyze the capability of a set of neurobiological and psychopathological variables to discriminate bulimia nervosa (BN) patients from healthy controls. METHOD: Seventy-five female patients with purging BN and 30 healthy controls were compared for psychopathology (impulsivity, borderline personality traits, depressive symptoms and self-defeating personality traits) and neurobiological parameters reflecting hypothalamic-pituitary-adrenal axis activity (morning serum cortisol before and after dexamethasone) and monoamine activity (24-hour urinary excretion of norepinephrine, serotonin, dopamine, and their main metabolites: 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid). Furthermore, the relationships between the 2 sets of variables were compared in the 2 samples. RESULTS: BN patients displayed higher impulsivity, more severe depressive features, and more borderline and self-defeating personality traits than controls. The 4 psychopathological variables were strongly interrelated in patients, whereas only depressive features correlated with self-defeating personality traits in controls. Patients had lower 24-hour excretion of serotonin and dopamine than controls, as well as lower ability to suppress cortisol. The relations between the biochemical and the psychopathological variables were only significant in the BN patients, but not in the control group. When discriminant analysis methods were applied, patients and controls differed for psychopathology (impulsive behaviors and borderline personality traits) and biological parameters (baseline cortisol and dopamine excretion), but when the variables were analyzed together, the differences in neurobiological parameters appeared as mediated by the psychopathological status. DISCUSSION: Our results suggest that hypothalamic-pituitary-adrenal axis activity, dopamine activity and other biological parameters are worthy of further study as potential dimensional markers of BN, although they seem to depend on the psychopathological status of the patients, in such a way that the psychopathological items associated with emotional instability (impulsivity and borderline personality traits) seem to be more reliable as clinical markers at the time being.

Bulimia nervosa with history of anorexia nervosa: could the clinical subtype of anorexia have implications for clinical status and treatment response?

OBJECTIVE: To investigate whether the subtype of anorexia nervosa (AN) could influence the bulimic syndrome and treatment response in bulimia nervosa (BN) patients with a history of AN (BN/AN+). METHOD: Seventy female BN patients were assessed for eating disorder, psychopathology and personality, and treated for 6 months. RESULTS: BN/AN+ patients retained some traits of their past condition: lower body weight, higher perfectionism, and higher reward dependence. They also had more severe symptoms, longer evolution time, and worse response to treatment. A history of restricting AN was associated to higher age, longer evolution time, higher impulsivity, and greater tendency to use diet pills and diuretics. A history of binge-purging AN was associated to more severe vomiting, lower body dissatisfaction and less depressive symptoms, as well as better outcome. DISCUSSION: The influence of the AN subtype in BN/AN+ patients is worthy of further study as it might have clinical implications.

The HLA-B*83:01 allele is generated by a gene conversion event including whole of exon 2 and partial introns 1 and 2 between B*44 and B*56 alleles.

Several studies have indicated the gene conversion as the most important mechanism about the MHC polymorphism generation when intron sequences are studied. The data obtained confirm that the B*83:01 allele is generated by gene conversion event including exon 2 and partial intron 1 and 2 between B*44 and B*56 alleles.

Atypical symptoms of gastro-esophageal reflux during pregnancy.

BACKGROUND: Pregnancy is associated with an increased incidence of heartburn. However, there is no information for other symptoms related to gastro-esophageal reflux (GOR). AIM: to assess the prevalence of atypical symptoms of GOR during pregnancy, and to examine its association with typical GOR symptoms. METHODS: we report data for 263 women with a pregnancy of less than 12 weeks. They were interviewed at the end of each trimester of pregnancy and at 1-year post-partum, using the Gastro Esophageal Reflux Questionnaire (GERQ). In the first interview, information about symptoms in the year before pregnancy was also collected with GERQ. RESULTS: women suffered atypical GOR symptoms during pregnancy more frequently than in the year before: non-cardiac chest pain (NCCP) (9.1 vs. 1.9%), dysphagia (12.6 vs. 2.3%), globus (33.1 vs. 4.6%), cough (26.6 vs. 6.8%), belching (66.2 vs. 19.4%) and hiccups (19.0 vs. 8.4%). Atypical GOR symptoms in pregnancy showed an association with suffering the same symptom before pregnancy and NCCP, globus, belching and hiccups with suffering typical GOR symptoms in the first trimester. CONCLUSIONS: Atypical GOR symptoms are highly prevalent in pregnancy, and are associated with atypical symptoms before pregnancy and with typical symptoms of GOR in the first trimester.

Variation of enterohepatic circulation observed with 75SeHCAT images in the first three hours. Scintigraphic patterns and analysis of their association with the diagnosis of bile acid malabsorption.

OBJETIVE: To evaluate the enterohepatic circulation of 75-Selenium turoselecolic acid (75Se-SeHCAT) during the first 3 h and its correlation with the abdominal retention at the 7th day (AR7), as contribution to the clinical study of biliar acid malabsorption (BAM). MATERIALS AND METHODS: 38 patients with chronic diarrhea were retrospectively studied. Acquisition protocol included static abdominal images at 1st, 2nd and 3rd hour and the 7th day after oral administration of the radiopharmaceutical. Images of 1-3 h determined 5 patterns of enterohepatic circulation that, due to their location, were characterized as: 1) gallbladder 2-3 h, 2) gallbladder 3 h, 3) gallbladder-abdomen 2-3 h, 4) abdomen, 5) upper left abdomen. The association of these patterns with the AR7 (Fisher, STATA) were investigated. Patients were classified as Non BAM (AR7 > 15%), mild-BAM (AR7 15-10%), moderate-BAM (AR7 10-5%) or severe-BAM (AR7 < 5%). RESULTS: 19 patients had an AR7 diagnostic of BAM (7 mild-BAM, 5 moderate-BAM, 7 severe-BAM). The pattern "gallbladder at 2-3 h" was statistically associated with Non BAM (p 0,008), while "gallbladder-abdomen at 2-3 h" was correlated with having BAM (p 0,029). CONCLUSION: Variations detected at the abdominal level in images during the first 3 h were associated with changes in intestinal absorption and the incorporation of the radiopharmaceutical into the pool of bile acids, so visual interpretation of the images at 2nd and 3rd hour could be useful in the final assessment of the study.

Variation of enterohepatic circulation through the image with 75SeHCAT in the first 3 hours. Scintigraphic patterns and análisis of its association with the diagnosis of bile acid malabsorption. / Variación de la circulación enterohepática a través de la imagen con 75SeHCAT en las 3 primeras horas. Patrones gammagráficos y análisis de su asociación con el diagnóstico de malabsorción de ácidos biliares.

OBJETIVE: To evaluate the enterohepatic circulation of 75-Selenium turoselecolic acid (75Se-SeHCAT) during the first 3 hours and its correlation with the abdominal retention at the 7th day (AR7), as contribution to the clinical study of biliar acid malabsorption (BAM). MATERIALS AND METHODS: 38 patients with chronic diarrhea were retrospectively studied. Acquisition protocol included static abdominal images at 1st, 2nd and 3rd hour and the 7th day after oral administration of the radiopharmaceutical. Images of 1 to 3 hours determined 5 patterns of enterohepatic circulation that, due to their location, were characterized as: 1) gallbladder 2-3 hours, 2) gallbladder 3 hours, 3) gallbladder-abdomen 2-3 hours, 4) abdomen, 5) upper left abdomen. The association of these patterns with the AR7 (Fisher, STATA) were investigated. Patients were classified as Non BAM (AR7>15%), mild-BAM (AR7: 15-10%), moderate-BAM (AR7: 10-5%) or severe-BAM (AR7<5%). RESULTS: 19 patients had an AR7 diagnostic of BAM (7 mild-BAM, 5 moderate-BAM, 7 severe-BAM). The pattern "gallbladder at 2-3 hours" was statistically associated with Non BAM (p 0,008), while "gallbladder-abdomen at 2-3 hours" was correlated with having BAM (p 0,029). CONCLUSION: Variations detected at the abdominal level in images during the first 3 hours were associated with changes in intestinal absorption and the incorporation of the radiopharmaceutical into the pool of bile acids, so visual interpretation of the images at 2nd and 3rd hour could be useful in the final assessment of the study.

Abiotic factors influencing soil microbial activity in the northern Antarctic Peninsula region.

Microorganisms play a key role in the carbon (C) cycle through soil organic matter (SOM). The rate of SOM mineralization, the influence of abiotic factors on this rate and the potential behaviour of SOM are of particular interest in the northern Antarctic Peninsula and offshore islands. This is one of the most rapidly warming regions on Earth with numerous ice-free areas, some with abundant wildlife and with the greatest known soil organic carbon (SOC) storage in Antarctica. The latter implies extended Antarctic summer conditions promote increased terrestrial plant growth and soil microbial activity (SMA). SMA, determined by respirometry, is a measure of ecosystem function, and depends on microclimatic conditions and soil environmental properties. SMA and the effect of abiotic variables have been analysed in locations with different soil types, on Cierva Point (Antarctic Peninsula), Deception Island and Fildes Peninsula (King George Island). Soil microbial biomass carbon (SMBC) ranged from 5.66 to 196.6 mg SMBC kg-1and basal respiration (BR) from 2.86 to 160.67 mg CO2 kg-1 d-1. SMBC and BR values were higher in Cierva Point, followed by Fildes Peninsula and Deception Island, showing the same trend of SOM abundance. Except for Cierva Point, low nitrogen, phosphorus and C concentrations were observed. SMBC/total organic carbon (TOC) levels indicated that SOC was recalcitrant and SOM content was closely related to the extent of vegetation cover observed in situ. High metabolic quotient values obtained at Cierva Point and Deception Island (median values 7.27 and 6.53 mg C-CO2 g SMBC-1 h-1) and low SMBC/TOC in Cierva Point suggest a poor efficiency of the microbial populations in the consumption of the SOC. High SMBC/TOC values obtained in Deception Island indicates that SMBC may influence SOM stabilization. Mineralization rates were very low (negligible values to 1.44%) and sites with the lowest values had the highest SOM.

A new allele, HLA-G*010120, is generated by a recombination event between HLA-G*01010101/02 and HLA-G*01010201.

Recombination between HLA-G*01010101/02 and HLA-G*01010201 generates HLA-G*010120.

Psychopathology and lymphocyte subsets in patients with bulimia nervosa.

The association between lymphocyte subsets and several psychopathological variables which had proved to be able to affect immune cell count in other conditions was investigated in bulimia nervosa patients. Sixty-seven female bulimia nervosa patients and 29 female healthy controls were assessed for nutritional status (weight, blood cells, lymphocyte subsets, biochemical parameters and hormones) and psychopathology (anxiety, depression, hostility, impulsivity and borderline personality traits). A negative correlation between impulsivity and helper T-cells (CD4(+)) was found in controls. In the bulimia nervosa group, the patients with higher anxiety had the lower lymphocyte count, and anxiety and hostility were negatively related to CD4(+) count. In addition, helper/cytotoxic T-cell ratio negatively correlated in this group with impulsivity, hostility and depression. In the light of these results, the potential influence of psychopathology on lymphocyte subset counts seems to be specific in bulimia nervosa patients, and more relevant than in healthy controls.

[Role of the renin-angiotensin system in pregnancy and preeclampsia]. / Papel del sistema renina-angiotensina en el embarazo y la preeclampsia.

The renin-angiotensin system (ARS) is a hormonal cascade that regulates blood pressure, electrolytes and water balance. AngiotensinII (AII) exerts its effects through the AT1 and AT2 receptors. AT1 is found in the syncytiotrophoblast, AT2 predominates during foetal development and its stimulation inhibits cell growth, increases apoptosis, causes vasodilation and regulates the development of foetal tissue. There is also an SRA in the placenta. The local generation of AII is responsible for the activation of AT1 receptors in the trophoblast. In normal pregnancy, concomitantly with reduction of blood pressure the circulating RAS increases, but blood pressure does not rise due to AII refractoriness, which does not occur in preeclampsia. We review the role of the SRA in normal pregnancy and preeclampsia.

A new allele, HLA-G*01010106, with changes in intron 2.

Three nucleotide changes and one insertion in intron 2 upon human leucocyte antigen (HLA)-G*01010105 generate HLA-G*01010106.

The novel HLA-G*01010302 allele differs from G*01010301 by a single nucleotide change in intron 5.

HLA-G*01010301 and G*01010302 differ by a single point mutation in intron 5.

Recognition and management of hereditary colorectal cancer syndromes.

Over 1,900 colorectal tumors will arise in association with a hereditary colorectal cancer syndrome in Spain in 2009. The genetic defects responsible for the most common syndromes have been discovered in recent years. Genetic testing helps diagnose affected individuals and allows identification of individuals at-risk. Colonoscopy and prophylactic colectomy decrease colorectal cancer incidence and overall mortality in patients with hereditary colon cancer. Extracolonic tumors are frequent in these syndromes, so specific surveillance strategies should be offered.

[Capsule endoscopy interpretation: the role of physician extenders]. / Interpretación de la cápsula endoscópica: el papel del personal no especializado.

BACKGROUND AND AIMS: capsule endoscopy (CE) allows for a new era in small-bowel examination. Nevertheless, physicians time for CE-interpretation remains longer than desirable. Alternative strategies to physicians have not been widely investigated. The aim of this study was to evaluate the accuracy of physician extenders in CE-interpretation. MATERIAL AND METHODS: one CE-experienced gastroenterologist and two physician extenders reviewed independently 20 CE-procedures. Each reader was blinded to the findings of their colleagues. A consensus formed by the readers and a second CE-experienced gastroenterologist was used as gold standard. Number, type and location of images selected, character of CE-exams and their relationship with indications were recorded. Gastric emptying time (GEt), small-bowel transit time (SBTt) and time spent by readers were also noted. RESULTS: sensitivity and specificity for "overall" lesions was 79 and 99% for the gastroenterologist; 86 and 43% for the nurse; and 80 and 57% for the resident. All 34 "major" lesions considered by consensus were found by the readers. Agreement between consensus and readers for images classification and procedures interpretation was good to excellent (? from 0.55 to 1). No significant differences were found in the GEt and SBTt obtained by consensus and readers. The gastroenterologist was faster than physician extenders (mean time spent was 51.9 +/- 13.5 minutes versus 62.2 +/- 19 and 60.9 +/- 17.1 for nurse and resident, respectively; p < 0.05). CONCLUSIONS: physician extenders could be the perfect complement to gastroenterologists for CE-interpretation but gastroenterologists should supervise their findings. Future cost-efficacy analyses are required to assess the benefits of this alternative.