Probabilistic tsunami forecasting for early warning.

Tsunami warning centres face the challenging task of rapidly forecasting tsunami threat immediately after an earthquake, when there is high uncertainty due to data deficiency. Here we introduce Probabilistic Tsunami Forecasting (PTF) for tsunami early warning. PTF explicitly treats data- and forecast-uncertainties, enabling alert level definitions according to any predefined level of conservatism, which is connected to the average balance of missed-vs-false-alarms. Impact forecasts and resulting recommendations become progressively less uncertain as new data become available. Here we report an implementation for near-source early warning and test it systematically by hindcasting the great 2010 M8.8 Maule (Chile) and the well-studied 2003 M6.8 Zemmouri-Boumerdes (Algeria) tsunamis, as well as all the Mediterranean earthquakes that triggered alert messages at the Italian Tsunami Warning Centre since its inception in 2015, demonstrating forecasting accuracy over a wide range of magnitudes and earthquake types.

Assessment of time intervals in the pathway to oral cancer diagnosis in north-westerm Spain. Relative contribution of patient interval.

BACKGROUND: Despite continuous advances in diagnosis and therapy, oral cancers are mostly diagnosed at advanced stages with minor survival improvements in the last two decades. Both phenomena have been attributed to delays in the diagnosis. This study aims at quantifying the time elapsed until definitive diagnosis in these patients and the patient interval's contribution. MATERIAL AND METHODS: A hospital-based, ambispective, observational study was undertaken on incident cases with a pathological diagnosis of oral squamous cell carcinoma recruited during 2015 at the Oral and Maxillofacial Surgery services of CHUAC (A Coruña) and POVISA (Vigo) hospitals. RESULTS: 74 consecutive oral cancer patients (59.5% males; median age: 65.0 years (IQ:57-74)) were studied. Most cases (52.7%; n=39) were at advanced stages (TNM III-IV) at diagnosis. The period since first sign/symptom until the patient seeks health care was the longest interval in the pathway to diagnosis and treatment (median: 31.5 days; IQR= 7.0 - 61.0) and represents >60% of the interval since symptom onset until referral to specialised care (pre-referral interval). The average interval assigned to the patient resulted to be relatively larger than the time elapsed since the patient is seen at primary care until a definitive diagnosis is reached (diagnostic interval). Median of the referral interval for primary care professionals: 6.5 days (IQR= 0.0 - 49.2) and accounts for 35% (19% - 51%) of the diagnostic interval. CONCLUSIONS: The patient interval is the main component of the pathway to treatment since the detection of a bodily change until the definitive diagnosis. Therefore, strategies focused on risk groups to shorten this interval should be implemented in order to ease an early diagnosis of symptomatic oral cancer.

Surgery and trauma care providers' perception of the impact of dual-practice employment on quality of care provided in an Andean country.

BACKGROUND: Dual-practice, simultaneous employment by healthcare workers in the public and private sectors is pervasive worldwide. Although an estimated 30 per cent of the global burden of disease is surgical, the implications of dual practice on surgical care are not well understood. METHODS: Anonymous in-depth individual interviews on trauma quality improvement practices were conducted with healthcare providers who participate in the care of the injured at ten large hospitals in Peru's capital city, Lima. A grounded theory approach to qualitative data analysis was employed to identify salient themes. RESULTS: Fifty interviews were conducted. A group of themes that emerged related to the perceived negative and positive impacts of dual practice on the quality of surgical care. Participants asserted that the majority of physicians in Lima working in the public sector also worked in the private sector. Dual practice has negative impacts on physicians' time, quality of care in the public sector, and surgical education. Dual practice positively affects patient care by allowing physicians to acquire management and quality improvement skills, and providing incentives for research and academic productivity. In addition, dual practice provides opportunities for clinical innovations and raises the economic status of the physician. CONCLUSION: Surgeons in Peru report that dual practice influences patient care negatively by creating time and human resource conflicts. Participants assert that these conflicts widen the gap in quality of care between rich and poor. This practice warrants redirection through national-level regulation of physician schedules and reorganization of public investment in health via physician remuneration.

Reliable methods for determination of triazine herbicides and their degradation products in seawater and marine sediments using liquid chromatography-tandem mass spectrometry.

Triazines and their degradation products are transported to the aquatic environment, and once there, the probability to reach the marine environment is very high. In this paper, solid phase extraction (SPE) and extraction by matrix solid phase dispersion (MSPD) to analyse nine triazines (ametryn, atrazine, cyanazine, prometryn, propazine, simazine, simetryn, terbuthylazine and terbutryn) and eight degradation products (desethylatrazine, desethyldesisopropylatrazine, desethyl-2-hydroxyatrazine, desethylterbuthylazine, desisopropylatrazine, desisopropyl-2-hydroxyatrazine, 2-hydroxyatrazine and 2-hidroxyterbuthylazine) in seawater and marine sediments samples were used. The analysis was carried out using liquid chromatography with tandem mass spectrometry (LC-ESI-MS/MS). The methods were optimized and validated to achieve a selective and sensitive determination of the analytes from different sample, regardless of its complexity. Under the optimum conditions, the proposed methods provided adequate limits of quantification (0.05-0.45 µg L-1 and 0.23-4.26 µg kg-1 in seawater and marine sediments, respectively). Intra- and inter-day relative standard deviation were below 1.41% for all compounds. Recoveries were evaluated, and acceptable values that ranged from 87.5-99.4 and 60.9-99.7% for the seawater and sediment samples, respectively, were obtained. The proposed methods were applied to the analysis of the target compounds in seawater samples and marine sediments from a coastal area of Galicia (NW of Spain).

On-line solid-phase extraction method for determination of triazine herbicides and degradation products in seawater by ultra-pressure liquid chromatography-tandem mass spectrometry.

A fast, simple, selective and sensitive method has been developed for the determination of nine triazine herbicides (ametryn, atrazine, cyanazine, prometryn, propazine, simazine, simetryn, terbuthylazine and terbutryn) and eight degradation products (desethyl atrazine, desethyl-desisopropyl atrazine, desethyl 2-hydroxyatrazine, desethyl terbuthylazine, desisopropyl atrazine, desisopropyl 2-hydroxyatrazine, 2-hydroxyatrazine and 2-hidroxyterbuthylazine) in seawater samples. On-line solid-phase extraction coupled with ultra-pressure liquid chromatography-tandem mass spectrometry was employed for simultaneous analysis of all compounds in 11min. Validation parameters were studied through the estimation of the limits of detection and quantification, calibration curves and precision. Limits of quantification ranged from 0.023 to 0.657µgL-1. Good linearity was obtained for all compounds with R2>0.99 in all cases. Furthermore, inter-day precision (0-2.1%) and intra-day precision (0-3.9%) were shown to be satisfactory. On-line solid-phase extraction recoveries in spiked unpolluted seawater sample were evaluated and acceptable values (80.3-99.8%) with adequate RSD (0.1-3.1%) were found. Finally, the proposed method was applied to the analysis of the target compounds in seawater samples collected from seawater nearby a zone of intensive horticulture of Matosinhos (Portugal). The concentrations of the herbicides were below the limit of detection in all cases.

Hypoxic induction of T-type Ca(2+) channels in rat cardiac myocytes: role of HIF-1α and RhoA/ROCK signalling.

T-type Ca(2+) channels are expressed in the ventricular myocytes of the fetal and perinatal heart, but are normally downregulated as development progresses. Interestingly, however, these channels are re-expressed in adult cardiomyocytes under pathological conditions. We investigated low voltage-activated T-type Ca(2+) channel regulation in hypoxia in rat cardiomyocytes. Molecular studies revealed that hypoxia induces the upregulation of Cav 3.2 mRNA, whereas Cav 3.1 mRNA is not significantly altered. The effect of hypoxia on Cav 3.2 mRNA was time- and dose-dependent, and required hypoxia inducible factor-1α (HIF-1α) stabilization. Patch-clamp recordings confirmed that T-type Ca(2+) channel currents were upregulated in hypoxic conditions, and the addition of 50 µm NiCl2 (a T-type channel blocker) demonstrated that the Cav 3.2 channel is responsible for this upregulation. This increase in current density was not accompanied by significant changes in the Cav 3.2 channel electrophysiological properties. The small monomeric G-protein RhoA and its effector Rho-associated kinase I (ROCKI), which are known to play important roles in cardiovascular physiology, were also upregulated in neonatal rat ventricular myocytes subjected to hypoxia. Pharmacological experiments indicated that both proteins were involved in the observed upregulation of the Cav 3.2 channel and the stabilization of HIF-1α that occurred in response to hypoxia. These results suggest a possible role for Cav 3.2 channels in the increased probability of developing arrhythmias observed in ischaemic situations, and in the pathogenesis of diseases associated with hypoxic Ca(2+) overload.

5-year mortality in cardiac surgery patients with low cardiac output syndrome treated with levosimendan: prognostic evaluation of nt-probnp and c-reactive protein.

AIM: To determine the clinical risk factors predictive of the 5--year mortality in patients with low cardiac output syndrome (LCOS) after cardiac surgery. In addition, to assess the influence of inflammation and myocardial dysfunction severity, as measured by C--reactive protein (CRP) and N--terminal pro--brain natriuretic peptide (NT--proBNP) concentrations, on outcome. METHODS: We studied 30 patients who underwent cardiac surgery and developed postoperative LCOS requiring inotropic support for longer than 48 hours after intensive care unit (ICU) admission. All patients received a 24--hour infusion of levosimendan after study enrolment. We measured the following at baseline, 24 h, 48 h and 7 days: clinical data, serum NT--proBNP and serum CRP levels. Patients were followed--up at 5 years for death by any cause. A risk--adjusted Cox proportional hazards regression model was used for statistical analysis. Hazard ratios and their 95% confidence intervals (CI) are presented. RESULTS: The 5--year mortality was 36.6% (n = 11). The predictors of 5--year mortality were the presence of dilated cardiomyopathy (HR = 36.909; 95% CI: 1.901-716.747; P = 0.017), a higher central venous pressure (CVP) at 48 hours (HR = 2.686; 95% CI: 1.383-5.214; P = 0.004), and lower CRP levels on day 7 (HR = 0.963; 95% CI: 0.933-0.994; P = 0.021). NT--proBNP levels showed a trend to higher initial levels in survivors without statistical significance, but were not associated with 5--year mortality. CONCLUSIONS: The presence of dilated cardiomyopathy, elevated CVP at 48 h and reduced CRP levels on day 7 predicted 5--year mortality in patients who developed postoperative LCOS after cardiac surgery. NT--proBNP levels in the first postoperative week were not predictors of long--term outcomes.

An environmentally friendly method for the determination of triazine herbicides in estuarine seawater samples by dispersive liquid-liquid microextraction.

A fast, simple, sensitive and green chemistry method using dispersive liquid-liquid microextraction (DLLME) for the simultaneous determination of seven triazine herbicides (ametryn, atrazine, cyanazine, propazine, simazine, simetryn and terbuthylazine) in estuarine seawater samples has been developed. DLLME was carried out using a small volume of seawater (25 mL) and 300 µL of 1-octanol. Herbicide concentrations were determined by liquid chromatography-diode array detection, and results were confirmed by liquid chromatography-electrospray ionisation tandem spectrometry analysis. The analytical features of the proposed method were satisfactory with repeatability < ±5% and intermediate precision < ±10%, and recoveries ranged from 81-102% for all compounds. All the triazines exhibited linear matrix calibration curves with coefficients of determination >0.999 for all the analytes except for simazine (0.9975). Limits of quantification ranged between 0.19 and 1.12 µg L(-1). The method was applied to the analysis of seawater samples from ten points susceptible to contamination by triazines from estuary of A Coruña (Galicia, NW of Spain). The levels of the seven triazines were below the LODs in the analysed samples. Use of proposed method will allow for monitoring of triazines at levels below the regulatory limits set by the European Directive 2008/105/EC of 2 and 4 µg L(-1) for atrazine and simazine, respectively.

Development of a Matrix Solid Phase Dispersion methodology for the determination of triazine herbicides in mussels.

A method based on Matrix Solid Phase Dispersion (MSPD) for determination of nine triazines in mussels has been optimised in terms of the sorbents used for extracting and cleaning-up. Two dispersing agents: C18 and florisil, and eight cleanup co-sorbents: florisil, silica, silica/alumina, Envi™ Carb, Envi-Carb-II/PSA, SAX/PSA, Envi-Carb-II /SAX/PSA and C18 were assayed. Analytes were eluted using 20 mL of ethyl acetate and 5 mL of acetonitrile and finally the extract was concentrated to dryness, re-constituted with 1 mL methanol and determined by HPLC-DAD. The best results were obtained with C18 as dispersing agent and Envi-Carb-II/SAX/PSA as clean-up co-column. Recoveries ranged between 79% and 99% and repeatability and reproducibility were below than 16% for all compounds. The linearity of the calibration curves yielded the R(2)⩾0.9993. The LOQ values ranged from 0.10 to 0.18 mg kg(-1) dried sample. Finally the method was applied to the analysis of mussel samples from Galicia (NW Spain).

Outcomes in weight loss, fasting blood glucose and glycosylated hemoglobin in a sample of 415 obese patients, included in the database of the European accreditation council for excellence centers for bariatric surgery with laparoscopic one anastomosis gastric bypass.

BACKGROUND: Obesity is a risk factor for the development of diseases such as type 2 Diabetes Mellitus. Bariatric surgery with laparoscopic single anastomosis gastric bypass is an effective treatment for morbid obesity and diabetes type 2 complete remission, and it has been proven to generate an improvement in glycemic levels and glycosylated hemoglobin (HbA1c) keeping the weight loss for a long time. MATERIAL AND METHODS: In a period of time between June 2002 until May 2012, 2070 patients underwent surgery with LOAGB technique. Between January 2010 an May 2012, 415 patients were included in the European Accreditation Council for Excellence Centers for Bariatric Surgery (EAC-BS) database, from which 79 patients with a glycemic level disturbance in the preoperative blood sample where chosen. Of this group, 47 patients were pre-diabetic (fast plasma glucose ≥ 110 mg/dl ≤ 125 mg/dl) and glycosylated hemoglobin (HbA1c) levels between 5.7-6.4% and 32 were diabetic (fast plasma glucose ≥ 126 mg/dl) and glycosylated hemoglobin (HbA1c) levels ≥ 6.5%. We described the weight evolution, the excess body mass index lost percentage (%EBMIL) the glycemia and the glycosylated hemoglobin levels; and we reported regular laboratory controls during the first year after surgical intervention. RESULTS: Both patient groups achieved their lowest mean weight loss 12 months after surgery, being average weight in the pre-diabetic group 62,41 ± 10,93 and 68,36 ± 11,16 in the diabetic group. Since 3 months after surgery, pre-diabetic patients achieve a mean BMI < 30, according to the Spanish Society for Obesity Study (SEEDO 2007) this amount is outside of the definition of obesity. Not being the case of the diabetic patients who don´t achieve this result until 6 months after surgery. The weight loss was excellent in both study groups, achieving an excess body mass index loss percentage (% EBMIL) greater than 65%, since the first three-month postoperative control. Glycemia levels descend in both groups, achieving the pre-diabetic group a mean glycemia level of < 110 mg/ dl in the second day after LOAGB surgery. Pre-diabetic patients maintain more stable glycemia with better controls, and very favorable outcomes 12 months after surgery. The diabetic patients achieve the mean glycemia level of < 110 mg/dl at the first month after surgery and maintained it 12 months after surgery which is the time of this study. The glycosylated hemoglobin levels descended in both groups, achieving levels of 4% three months after surgery in the prediabetic group and 4.8% at six months in the diabetic group. CONCLUSION: LOAGB proved to be an efficient bariatric technique for complete remission of pre-diabetes and diabetes mellitus type 2 and also with the excess weight loss resolution. We showed that the excess weight loss, the glycemia and glycosylated hemoglobin levels continue being normal after one year of follow up after surgery. The best results are obtained in pre-diabetic patients who underwent LOAGB, this group is integrated with people who are at high risk of suffering a deterioration of their obesity and a rapid advance of the diabetes and the associated comorbidities, that's why surgery has to be performed as soon as possible when the medical exam continues being favorable.

Introducción: La obesidad es un factor de riesgo para el desarrollo de enfermedades tales como la diabetes mellitus tipo II. La cirugía bariátrica laparoscópica de una anastomosis también conocida como mini-bypass con las modificaciones del doctor Carbajo, es un tratamiento efectivo para el manejo de la obesidad mórbida y para obtener una completa remisión de la diabetes tipo II y se ha demostrado que se genera una mejoría de los niveles de glicemia y de hemoglobina glicosilada (HbA1c) manteniendo la pérdida de peso por un largo período de tiempo. Material y métodos: En un período de tiempo entre junio del 2002 hasta mayo de 2012, 2070 pacientes se intervinieron quirúrgicamente con la técnica bariátrica laparoscópica de una anastomosis gástrica (BAGUA). Entre enero de 2010 y mayo de 2012, 415 pacientes fueron incluidos en la base de datos del Consejo Europeo de acreditación para centros de excelencia de cirugía bariátrica, de los cuales se escogieron 79 pacientes que presentaban trastornos de los niveles de glicemia en sus pruebas sanguíneas preoperatorias. De este grupo 47 pacientes se clasificaron como pre-diabéticos con niveles de glucosa en sangre ≥110 mg/ dl ≤ 125 mg/dl y unos niveles de hemoglobina glicosilada ( HbA1C) entre 5.7-6.4% y 32 como diabéticos con niveles de glucosa en sangre ≥ 126 mg/dl y niveles de hemoglobina glicosilada (HbA1C) ≥ 6.5%. Nosotros describimos la evolución de los cambios en el peso, el porcentaje de pérdida del índice de masa corporal, los niveles de glicemia y de hemoglobina glicosilada de los pacientes estudiados y reportamos los resultados de los controles de laboratorio practicados regularmente durante el primer año postoperatorio. Resultados: ambos grupos de pacientes alcanzaron su máxima pérdida de peso a los 12 meses postoperatorios, siendo el peso promedio en el grupo de pre-diabéticos 62,41 ± 10,93 y 68,36 ± 11,16 en el grupo de diabéticos. Los pacientes pre-diabéticos alcanzaron desde los 3 meses de postoperatorio un índice de masa corporal (IMC) < 30, que de acuerdo con el estudio sobre Obesidad de la Sociedad Española (SEEDO 2007) esta cantidad se encuentra por fuera de la definición de obesidad, no siendo el caso del grupo de pacientes diabéticos que no alcanzaron este resultado hasta los 6 meses de postoperatorio. La pérdida de peso fue excelente en ambos grupos alcanzando un porcentaje de pérdida de índice de masa corporal mayor de 65% desde los primeros 3 meses de control postoperatorio. Los niveles de glicemia bajaron en ambos grupos, alcanzando el grupo de pre-diabéticos un nivel de glicemia < 110 mg/dl desde el segundo día postoperatorio de BAGUA. Los pacientes pre-diabéticos mantuvieron un nivel de glicemia estable con mejor control y una muy favorable evolución a los 12 meses de postoperatorio. Los pacientes diabéticos alcanzaron el nivel de glicemia < 110 mg/dl en el primer mes postoperatorio y lo mantuvieron así a los 12 meses de postoperatorio, tiempo en el que se elaboró este estudio. Los niveles de hemoglobina glicosilada descendieron en ambos grupos, alcanzando niveles de 4% a los 3 meses de postoperatorio en los pacientes prediabéticos y un 4,8% a los 6 meses en el grupo de los pacientes diabéticos. Conclusión: BAGUA mostró ser una técnica quirúrgica bariátrica eficiente para la remisión completa de la pre-diabetes y la diabetes tipo II así como de la pérdida del exceso de peso. Nosotros demostramos que la pérdida del exceso de peso, los niveles de glicemia y de hemoglobina glicosilada continuaron siendo normales al año de seguimiento postoperatorio. Los mejores resultados se obtuvieron en el grupo de pre-diabéticos a quienes se les practicó BAGUA. Este grupo está integrado por personas que se encuentran en riesgo de sufrir un deterioro de su obesidad y un rápido avance hacia diabetes y a las comorbilidades asociadas, está es la razón por la cual esta cirugía debe realizarse lo más pronto posible mientras las pruebas médicas de los pacientes sigan siendo favorables.

Determination of triazine herbicides in seaweeds: development of a sample preparation method based on Matrix Solid Phase Dispersion and Solid Phase Extraction Clean-up.

A method using dual process columns of Matrix Solid Phase Dispersion (MSPD) and Solid Phase Extraction (SPE) has been developed for extracting and cleaning-up of nine triazine herbicides (ametryn, atrazine, cyanazine, prometryn, propazine, simazine, simetryn, terbuthylazine and terbutryn) in seaweed samples. Under optimized conditions, samples were blended with 2g of octasilyl-derivatized silica (C8) and transferred into an SPE cartridge containing ENVI-Carb II/PSA (0.5/0.5 g) as a clean up co-sorbent. Then the dispersed sample was washed with 10 mL of n-hexane and triazines were eluted with 20 mL ethyl acetate and 5 mL acetonitrile. Finally the extract was concentrated to dryness, re-constituted with 1 mL methanol:water (1:1) and injected into the HPLC-DAD system. The linearity of the calibration curves was excellent in matrix matched standards, and yielded the coefficients of determination>0.995 for all the target analytes. The recoveries ranged from 75% to 100% with relative standard deviations lower than 7%. The achieved LOQs (<10 µg kg(-1)) for all triazines under study permits to ensure proper determination at the maximum allowed residue levels set in the European Union Legislation. Samples of three seaweeds were subjected to the procedure proving the suitability of MSPD method for the analysis of triazines in different seaweeds samples.

First Report of Fusarium temperatum Causing Seedling Blight and Stalk Rot on Maize in Spain.

In Europe, several diseases of maize (Zea mays L.) including seedling blight and stalk rot are caused by different Fusarium species, mainly Fusarium graminearum, F. verticillioides, F. subglutinans, and F. proliferatum (3). In recent years, these Fusarium spp. have received significant attention not only because of their impact on yield and grain quality, but also for their association with mycotoxin contamination of maize kernels (1,4). From October 2011 to October 2012, surveys were conducted in a maize plantation located in Galicia (northwest Spain). In each sampling, 100 kernels and 10 maize stalks were collected from plants exhibiting symptoms of ear and stalk rot. Dried kernels and small stalk pieces (1 to 2 cm near the nodes) were placed onto potato dextrose agar medium and incubated in the dark for 7 days. Fungal colonies displaying morphological characteristics of Fusarium spp. (2) were subcultured as single conidia onto SNA (Spezieller Nahrstoffarmer agar) (2) and identified by morphological characteristics, as well as by DNA sequence analysis. A large number of Fusarium species (F. verticillioides, F. subglutinans, F. graminearum, and F. avenaceum) (1,2) were identified. These Fusarium species often cause ear and stalk rot on maize. In addition, a new species, F. temperatum, recently described in Belgium (3), was also identified. F. temperatum is within the Gibberella fujikuroi species complex and is morphologically and phylogenetically closely related to F. subglutinans (2,3). Similar to previous studies (3), our isolates were characterized based on the presence of white cottony mycelium, becoming pinkish white. Conidiophores were erect, branched, and terminating in 1 to 3 phialides. Microconidia were abundant, hyaline, 0 to 2 septa; ellipsoidal to oval, produced singly or in false heads, and on monophialides, intercalary phialides, and polyphialides. Microconidia were not produced in chains. No chlamydospores were observed (3). Macroconidia in carnation leaf agar medium (2) were hyaline, 3 to 6 septate, mostly 4, falcate, with a distinct foot-like basal cell (2,3). DNA was amplified with primers ITS1/ITS4 and EF1/EF2 (3). Partial sequences of gene EF-1α showed 100% homology with F. temperatum (3) (GenBank Accession Nos. HM067687 and HM067688). DNA sequences of EF-1α gene and ITS region obtained were deposited in GenBank (KC179824, KC179825, KC179826, and KC179827). Pathogenicity of one representative isolate was confirmed using a soil inoculation method adapted from Scauflaire et al., 2012 (4). F. temperatum isolate was cultured on sterile wheat grains. Colonized wheat grains (10 g) were mixed with sterilized sand in 10 cm diameter pots. Ten kernels per pot were surface disinfected in 2% sodium hypochlorite for 10 min, rinsed with sterilized water, drained (4), placed on the soil surface, and covered with a 2 cm layer of sterilized sand. Five pots were inoculated and five uninoculated controls were included. Pots were maintained at 22 to 24°C and 80% humidity for 30 days. Seedling malformations, chlorosis, shoot reduction, and stalk rot were observed on maize growing in inoculated soil and not from controls. F. temperatum was reisolated from the inoculated seedlings but not from the controls. References: (1) B. J. Bush et al. Phytopathology 94:88, 2003. (2) J. F. Leslie et al. The Fusarium Laboratory Manual, page 388. Blackwell Publishing, 2006. (3) J. Scauflaire et al. Mycologia 103:586, 2011. (4) J. Scauflaire et al. Eur. J. Plant Pathol. 133:911, 2012.

Prospective study of biomarkers of immune response in lung transplant recipients.

INTRODUCTION: Studies on biomarkers of tolerance in organ transplantation have been widely performed during the last decade. AIM: To assess biomarkers in relation to evolution of the immune response among lung transplant recipients. METHODS: This multicenter study included 27 lung transplant recipients followed before as well as at 7, 14, 30, 60, 90, and 180 days posttransplantation. Biomarkers of the immune response based on flow cytometry technology were validated in each center. They included intracellular cytokine expression, regulatory T-cell level, as well as lymphocyte surface antigen and CD28 expressions. RESULTS: The 13 patients who developed acute rejection episodes showed increased numbers of regulatory T cells at 12 months posttransplant. Sixteen patients experiencing infections displayed decreased expression of CD69 on CD8 T cells within the first year of follow-up. CONCLUSION: High Treg levels in the peripheral blood of lung transplant recipients were associated with an increased risk of rejection but not infection. Inversely, we observed low levels of activated CD8 T cells in infected patients.

Interaction of -55CT polymorphism of UCP3 gene with Trp64Arg polymorphism of beta3adrenoreceptor gene on insulin resistance in obese patients.

BACKGROUND: The aim of our study was to investigate the interaction of tryptophan-to-arginine (Trp64Arg) missense mutation in the beta3 adrenoreceptor (Beta3AR) with polymorphism in the UCP3 promotor (-55C->T) on insulin resistance in obese patients. DESIGN: A population of 212 obese patients was analyzed. A bipolar electrical bioimpedance, a biochemical analysis and concentrations of adipocytokines were assessed. RESULTS: One hundred and sixty-two patients (76.4%) had the genotype Trp64/Trp64 (wild type group) and 50 patients Trp64/Arg64 (23.6%) (mutant type group). One hundred and seventy five (87.2%) had the genotype -55CC (wild type group) and 27 patients (22.8%) -55CT (mutant type group). Five patients (2.4%) had both polymorphisms Trp64/Arg64 and -55CT. Patients with one or both mutant genotypes had higher BMI, weight, fat mass, systolic blood pressure and waist circumference than wild type patients. Patients with 55CT or 55CT and Trp64Arg genotype had higher BMI, weight, fat mass, waist circumference, waist to hip ratio glucose, insulin, triglycerides and HOMA than wild type or Trp64Arg mutation. CONCLUSION: Higher concentrations of insulin, HOMA, triglycerides, glucose, BMI, weight, fat mass, waist to hip ratio and waist circumference were observed in patients with -55CT genotype alone or -55CT plus Trp64Arg genotypes than in patients without mutation or only Trp64Arg mutation.

Relationship among metabolic syndrome, C358A polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) and insulin resistance.

BACKGROUND: It has been demonstrated that the polymorphism 385 C/A of FAAH (fatty acid amide hydrolase) was associated with obesity and metabolic disorders. OBJECTIVE: The aim of our study was to investigate the relationship of the polymorphism (cDNA 385 C->A) of FAAH gene and insulin resistance in obese patients with and without metabolic syndrome. DESIGN: A population of 799 obese patients was analyzed in cross-sectional survey. A bioimpedance, blood pressure, serial assessment of nutritional intake with 3 days written food records and biochemical analysis were performed. Genotype of FAAH gene polymorphism was studied. RESULTS: Prevalence of metabolic syndrome (MS) with ATP III definition was 49.8% (398 patients) and 50.2% patients without MS (n=401 patients). Prevalence of FAAH genotypes was similar in patients with metabolic syndrome (69.6% wild genotype and 30.4% mutant genotype) and without metabolic syndrome (66.6% wild genotype and 33.4% mutant genotype). In patients without metabolic syndrome, insulin and HOMA levels were higher in mutant genotype than wild type group. CONCLUSION: The main finding is the lack of association of the FAAH genotypes with metabolic syndrome prevalence. Patients with mutant genotype group of FAAH gene and without metabolic syndrome have higher insulin and HOMA levels than wild type group.

Importance of assessing CK19 immunostaining in core biopsies in patients subjected to sentinel node study by OSNA.

Analysis of sentinel lymph node (SLN) by means of One-Step Nucleic Acid Amplification (OSNA) is being used increasingly as a very sensitive and quick method for intraoperative axillary staging in patients with breast cancer. This molecular diagnostic assay detects the expression level of cytokeratin 19 (CK19), a luminal epithelial cell marker broadly expressed in most breast carcinomas and not normally found in lymph nodes. Almost all breast cancers express this cytoskeleton protein, but some breast tumors have been found to lose the expression of CK19. CK19 immunostaining in core biopsies has been recommended in selecting patients eligible for OSNA analysis because SLNs with metastatic involvement by CK19-negative breast cancers may result in a false negative result by OSNA. However, the real frequency of CK19-negative breast cancer has to be elucidated. In this study, we have assessed the frequency and molecular profile of CK19-negative breast carcinomas in three series of cases. The first is a prospective series of 197 breast carcinomas, 111 of which were subjected to SLN evaluation by OSNA. The second is a retrospective series of 41 triple-negative (TN) breast carcinomas, and the third is a retrospective series of 68 breast cancer patients (matched core biopsies and metastatic lymph nodes) that had been evaluated by conventional procedures before the OSNA methodology was adopted in our institution. Our results not only demonstrate that lack of expression of CK19 is infrequent in breast cancers but also that performing CK19 immunohistochemical staining is important on diagnostic core biopsies in taking the decision of using OSNA methodology in the evaluation of sentinel nodes in breast cancer patients.

Lys656Asn polymorphism of leptin receptor gene and metabolic syndrome in obese patients.

BACKGROUND: The etiology of common obesity is complex, because many genetic, environmental and metabolic factors might act. Alterations of the normal leptin receptor gene be involved in the development of obesity. The polymorphism on codon 656 produces a change in charge, making this change a possibility to be functional. OBJECTIVE: The aim of our study was to investigate the relationship between metabolic syndrome and Lys656Asn polymorphism in obese patients. DESIGN: A population of 714 obese patients (body mass index > 30) was analyzed in cross-sectional survey. A bioimpedance, blood pressure, a serial assessment of nutritional intake with 3 days written food records and biochemical analysis were performed. RESULTS: Four hundred and seventy eight patients (66.9%) had the genotype Lys656/Lys 656 (wild group), whereas 236 (33.1%) had either the genotype Lys656/Asn656 (212 patients, 29.7%) or the genotype Asn656/Asn656 (24 patients, 3.4%) (mutant group). Prevalence of metabolic syndrome (MS) with ATP III definition was 49.4% (353 patients; 35.1% males and 64.9% females) and 50.6% patients without MS (n = 361; 25.2% males and 75.8% females). Prevalence of leptin receptor (LEPR) genotypes was similar in patients with metabolic syndrome (65.5% wild genotype and 34.5% mutant genotype) and without metabolic syndrome (68.3% wild genotype and 31.7% mutant genotype). No differences in anthropometric and biochemical parameters were detected between genotypes in the same group of metabolic syndrome. CONCLUSION: The finding of our study is the lack of association of the Lys656/Asn656 and Asn656/ Asn656 genotypes with metabolic syndrome.

Circulating adipocytokines in morbid obese patients, relation with cardiovascular risk factors and anthropometric parameters.

BACKGROUND: Obesity and insulin resistance are associated with cardiovascular risk factors, including adipocytokines. The aim of the present study was to explore the relation of circulating adipocytokines with cardiovascular risk and anthropometric parameters in morbid obese patients. SUBJECTS: A population of 65 morbid obese patients was analyzed in a prospective way. A biochemical, anthropometric and dietary evaluation was realized. RESULTS: In the multivariate analysis with resistin as dependent variable, the BMI remained in the model (F = 16.6; p < 0.05), with an increase of 0.23 (CI 95%: 0.06-0.41) ng/ml with each point of BMI. In a second model with adiponectin as dependent variable, the age remained in the model (F = 4.46; p < 0.05), with an increase of 3.62 (CI 95%: 0.05-7.21) ng/ml with each year. In the third model with interleukin 6 as dependent variable, the HOMA, CRP and weight remained in the model (F = 8.8; p < 0.01), with an increase of 0.26 (CI 95%: 0.05-0.47) pg/ml with each point of HOMA, an increase of 0.43 (CI 95%: 0.10-0.76) pg/ml with each 1 mg/dl of CRP and an increase of 0.13 (CI 95%: 0.05-0.21) pg/ml with each kg of weight. In the fourth model with TNF-alpha as dependent variable, resistin, IL-6 and weight remained in the model (F = 5.2; p < 0.01), with an increase of 1.49 (CI 95%: 0.46-2.53) pg/ml with each point of resistin, an increase of 1.20 (CI 95%: 0.38-2.10) pg/ml with each 1 pg/dl of IL-6 and an increase of 0.27 (CI 95%: 0.04-0.51) pg/ml with each kg of weight. In the fifth model with leptin as dependent variable, BMI and TNF-alpha remained in the model (F = 4.1; p < 0.01), with an increase of 10.35 (CI 95%: 4.10-21.12) ng/ml with each point of BMI and a decrease of 10.16 (CI 95%: -20.37-0.76) pg/ml with each 1 pg/dl of TNF-alpha. CONCLUSION: Circulating adipocytokine concentrations are associated with different cardiovascular risk factors and anthropometric variables in morbid obese patients.

Effects of olmesartan vs irbesartan on metabolic parameters and visfatin in hypertensive obese women.

BACKGROUND: Angiotensin II regulates the production of adipokines. The objective was to study the effect of treatment with irbesartan versus olmesartan in obese hypertensive women. SUBJECTS: A sample of 34 obese hypertensive women was analyzed in a prospective way with a randomized trial. Patients were randomized to irbesartan (300 mg/day) or olmesartan (40 mg/day) for 3 months. Weight, body mass index, blood pressure, basal glucose, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, HOMA and visfatin were determined at basal time and after 3 months of treatment. RESULTS: Thirty four patients gave informed consent and were enrolled in the study. A significative decrease in systolic and diastolic blood pressures was reached without changes in weight. Patients treated with olmesartan had a significative decrease of total cholesterol, LDL cholesterol, insulin, HOMA and visfatin levels. Decrease in total cholesterol and LDL cholesterol was similar with both angiotensin receptor blockers. Decrease in insulin (2.28 +/- 2.77 vs 0.66 +/- 4.4 mUI/L: p < 0.05), HOMA (0.69 +/- 1.1 vs 0.48 +/- 1.6 units: p < 0.05) and visfatin (5.16 +/- 13 vs 1.85 +/- 9.1 ng/ml: p < 0.05) levels was higher in olmesartan than irbesartan group. CONCLUSION: The administration of olmesartan improved blood pressure, insulin, HOMA, visfatin and lipid profile in hypertensive obese women. Irbesartan improved blood pressure and lipid levels.

Effect of gonadotropin treatment on estrus, ovulation, and litter size in weaned and anestrous sows.

In the first of 2 experiments, we evaluated the effects on anestrous sows of pretreatment with FSH to stimulate the growth of small follicles, followed by eCG to stimulate the growth of medium follicles, estrus, and ovulation. In Exp. 2, we examined the effect of sows receiving 400 IU of eCG plus 200 IU of hCG (PG 600, Intervet/Schering Plough Animal Health, Boxmeer, the Netherlands) at weaning and then different doses and timing of supplemental hCG. In Exp. 1, a total of 87 multiparous Hypor sows deemed anestrus 7 d after weaning were assigned to intramuscular (i.m.) injection of 1) PG 600, 2) eCG (600 IU), 3) pretreatment with 87.5 IU of FSH on d 7 and 8 plus eCG on d 9, or were 4) noninjected controls. Sows had daily boar contact for 15 d after weaning for estrus detection. Blood samples were obtained on d 9 and 19 and assayed for progesterone to determine ovulation status. The weaning-to-estrus interval, number of sows in estrus and ovulating, farrowing rate, and litter size were not different (P > 0.1) in treated groups compared with controls. In Exp. 2, a total of 247 Hypor sows were assigned at weaning by parity (1 and 2 or > or = 3) to receive 1) an i.m. injection of PG 600, 2) PG 600 supplemented with 100 IU of hCG injected either concurrently or after 24 h, 3) 200 IU of hCG after 24 h, or 4) no injection (controls). Sows were exposed to boars daily for 7 d. After treatment of parity 1 and 2 sows, all gonadotropin-treated groups had an increased (P < 0.05) number of sows in estrus compared with the control group; weaning-to-estrus interval, farrowing rates, and litter size were unaffected (P > 0.1). After treatment of parity > or = 3 sows, there was no treatment effect on the estrous response and weaning-to-estrus interval; compared with control and PG 600-treated sows, farrowing rate was decreased (P < 0.05) for sows receiving 200 IU of hCG after 24 h. There was no effect (P > 0.1) of treatment on litter size. We conclude that gonadotropins can be used to increase estrus response in weaned sows, but that hCG treatment subsequent to PG 600 may be detrimental to sow fertility in parity > or = 3 sows.