Particle and metal exposure in Parisian subway: Relationship between exposure biomarkers in air, exhaled breath condensate, and urine.

Subway particulate toxicity results from in vitro and in vivo studies diverge and call for applied human research on outcomes from chronic exposures and potential exposure biomarkers. We aimed to (1) quantify airborne particulate matter (PM) concentrations (mass and number) and metal concentrations in exhaled breath condensate (EBC), urine, and PM; (2) investigate their associations (EBC vs. PM vs. urine); and (3) assess the relevance of EBC in biomonitoring. Nine subway workers in three jobs: station agents, locomotive operators and security guards were monitored during their 6-h shifts over two consecutive weeks. Six-hour weighed average mass concentrations expressed as PM10, PM2.5 and their metal concentrations were determined. Urine and EBC samples were collected pre- and post-shift. Ultrafine particle (UFP) number concentrations were quantified in PM and EBC samples. Metal concentrations in urine and EBC were standardized by creatinine and EBC volume, respectively, and log-transformed. Associations were investigated using Pearson correlation and linear mixed regression models, with participant's ID as random effect. PM concentrations were below occupational exposure limits (OEL) and varied significantly between jobs. Locomotive operators had the highest exposure (189 and 137 µg/m3 for PM10 and PM2.5, respectively), while station agents had the highest UFP exposure (1.97 × 104 particles/cm3). Five metals (Al, Fe, Zn, Cu, and Mn) in PM2.5 and three (Al, Fe, and Zn) in PM10 were above the limit of quantification (LOQ). Fe, Cu, Al and Zn were the most abundant by mass fraction in PM. In EBC, the metal concentrations in decreasing order were: Zn > Cu > Ni > Ba > Mn. Security guards had the highest EBC metal concentrations, and in particular Zn and Cu. Urinary metal concentrations in decreasing order were: Si > Zn > Mo > Ti > Cu > Ba ≈ Ni > Co. All urinary metal concentrations from the subway workers were similar to concentrations found in the general population. A statistically significant relationship was found for ultrafine particle number concentrations in PM and in EBC. Zn and Cu concentrations in post-shift EBC were associated with Zn and Cu concentrations in PM10 and with post-shift urinary Zn and Cu concentrations. Therefore, EBC appears a relevant matrix for assessing exposure to UFP in human biomonitoring when inhalation is a primary route of exposure. We found different temporal variation patterns between particle and metal exposures in three matrices (PM, urine, EBC) quantified daily over two full weeks in subway workers. These patterns might be related to metal oxidation, particulates' solubility and size as well as their lung absorption capabilities, which need to be further explored in toxicological research. Further research should also focus on understanding possible influences of low chronic exposures to subway particulates on health in larger cohorts.

Evaluation of a Cooperia oncophora double-domain ASP-based vaccine against Cooperia spp. infections in cattle and sheep.

A double-domain activation-associated secreted protein (dd-Co-ASP) isolated from the bovine small intestinal parasite Cooperia oncophora was previously shown to be an effective vaccine candidate to protect calves against a homologous challenge infection. The aim of this study was to investigate whether the dd-Co-ASP protein, purified from a Belgian C. oncophora isolate, would offer protection against a C. oncophora isolate from the southern hemisphere as well as other Cooperia species such as C. punctata in cattle and C. curticei in sheep. Two vaccination studies were performed, i.e. one in cattle and one in sheep, in which the protective effects of dd-Co-ASP, supplemented with Quil A as an adjuvant, were compared with an adjuvant control. Whereas our results showed a 75 % reduction in Cooperia spp. cumulative faecal egg counts, the results obtained in sheep demonstrated that dd-Co-ASP was ineffective in raising a protective immune response against a C. curticei challenge infection. Even though sequence analysis of the dd-Co-ASP gene revealed restricted sequence heterogeneity in the double domain ASP within and between bovine Cooperia species, the results of the vaccine study suggest that there is sufficient conservation at the protein level to yield cross-protection, holding promise for the development of a general Cooperia vaccine for use in cattle.

Respiratory Disease Occupational Biomonitoring Collaborative Project (ROBoCoP): A longitudinal pilot study and implementation research in the Parisian transport company.

The ROBoCoP project is launched within the EU COST Action CA16113 "CliniMARK" aiming to increase the number of clinically validated biomarkers and focused on chronic obstructive pulmonary disease (COPD) biomarker development and validation. ROBoCoP encompasses two consecutive studies consisting of a pilot study followed by a field study. The pilot study is a longitudinal exposure assessment and biomarker study aiming at: 1-understanding the suitability of the candidate biomarkers in surveying populations at risk such as workers exposed to COPD causing agents; 2-determining the best sampling plan with respect to the half-life of the candidate biomarkers; 3-implementing and validating the sampling procedures and analytical methods; 4-selecting the best suitable biomarkers to be measured in the field. Each study participant is surveyed every day during the 6-8 h work-shifts for two consecutive weeks. The field study has an implementation research designe that enabled us to demonstrate the applicability of the standardized protocol for biomarker measurements in occupational settings while also assessing the biomarkers' validity. ROBoCoP will focus on particulate matter (PM) exposure measurements, exposure biomarkers and a series of effect biomarkers, including markers of lipoperoxidation: 8-isoprostane, malondialdehyd in exhaled breath condensate (EBC) and urine, potential markers of nitrosative stress: NO2-, NO3- and formate anion in EBC; markers of DNA oxidation: 8-hydroxy-2'deoxyguanosine in EBC and urine, marker of genotoxicity: micronuclei in buccal cells, and oxidative potential in exhaled air (OPEA). OPEA appears particularly promising as a clinical biomarker for detecting COPD, and will be tested independently and as part of a biomarker panel. COPD diagnosis will be performed by an experienced occupational physician according to international diagnostic standards and confirmed by a pulmonologist.This research will include approximatively 300 underground subway workers randomly selected from the personnel registry of a large Parisian transport company. Underground subways are suggested as the most PM polluted urban transport environment. We believe this occupational exposure is relevant for biomonitoring of workers and early detection of respiratory diseases.

Remediation of mining soils by combining Brassica napus growth and amendment with chars from manure waste.

Mining activities lead to important physical, chemical and biological effects on soil properties, generating severe impacts in the establishment and maintenance of vegetation. Assisted phytoremediation can be considered an environmentally friendly approach for soil remediation. In this study, two mining soils (PORT and GAM) were treated with 10%, by mass, of the following amendments: manure biochars prepared at 450 °C (BMW450) and 600 °C (BMW600), hydrochars prepared by hydrothermal carbonization (HTC) of manure at 190 °C (HWM190) and 240 °C (HMW240) and manure waste (MW). Brassica napus was used as a phytoextraction species. After 45 days of plant growth, soil samples were widely characterized, including microbial biomass carbon, enzymatic activity and metal content. In addition, plant biomass production, bioconcentration factor, translocation factor and metal uptake were determined. Experimental results showed that addition of biochars improved the As uptake by Brassica napus in both soils but just in the roots increasing bioconcentration factor between 22.1 and 39.5% for GAM soil and between 28.6 and 53.4% for PORT soil. Brassica napus cannot be considered as Zn accumulator in GAM soil samples and in the case of PORT samples, only the addition of BMW600 and HMW240 enhanced the phytoextraction process of Zn on the roots. Soil enzyme activity improved in hydrochar amended soils.

Does exposure to inflammatory particles modify the pattern of anion in exhaled breath condensate?

Exposure to environmental and occupational particulate matter (PM) induces health effects on the cardio-pulmonary system. In addition, associations between exposure to PM and metabolic syndromes like diabetes mellitus or obesity are now emerging in the literature. Collection of exhaled breath condensate (EBC) is an appealing non-invasive technique to sample pulmonary fluids. This hypothesis-generating study aims to (1) validate an ion chromatography method allowing the robust determination of different metabolism-related molecules (lactate, formate, acetate, propionate, butyrate, pyruvate, nitrite, nitrate) in EBC; (2) apply this method to EBC samples collected from workers exposed to quartz (a known inflammatory particle), to soapstone (a less inflammatory particle than quartz), as well as to controls. A multi-compound standard solution was used to determine the linearity range, detection limit, repeatability and bias from spiked EBC. The biological samples were injected without further treatment into an ion chromatograph with a conductivity detector. RTube® were used for field collection of EBC from 11 controls, 55 workers exposed to soapstone and 12 volunteers exposed to quartz dust. The analytical method used proved to be adequate for quantifying eight anions in EBC samples. Its sub-micromolar detection limits and repeatability, combined with a very simple sample preparation, allowed an easy and fast quantification of different glycolysis or nitrosative stress metabolites. Using multivariate discriminant analysis to maximize differences between groups, we observed a different pattern of anions with a higher formate/acetate ratio in the EBC samples for quartz exposed workers compared to the two other groups. We hypothesize that a modification of the metabolic signature could be induced by exposure to inflammatory particles like quartz and might be observed in the EBC via a change in the formate/acetate ratio.

Diagnóstico de la dinámica cardiaca durante 16 horas desde los sistemas dinámicos aplicable en UCI / Diagnosis of cardiac dynamics for 17 hours from dynamical systems applicable to ICU

RESUMEN Introducción: El comportamiento caótico de la dinámica cardiaca normal y aguda ha sido caracterizado en el contexto de la teoría de los sistemas dinámicos y la geometría fractal. Objetivo: Desarrollar una nueva metodología diagnóstica para la evaluación de la dinámica cardiaca en pacientes de UCI, durante 16 horas. Metodología: Este es un estudio en pacientes ingresados a Cuidados Intensivos posquirúrgicos (UCI) y sujetos sanos, tomando un total de 47 registros electrocardiográficos continuos y/o Holter, normales y con patología aguda, evaluados en 16 horas. Se desarrolló una inducción con dos dinámicas normales y tres de UCI; a partir de los valores máximos y mínimos de la frecuencia cardiaca/hora y total de latidos/hora, registrados durante 16 horas se construyeron atractores para evaluar sus espacios de ocupación y dimensión fractal, con el fin de establecer diferencias e igualdades respecto a estados normales y patológicos. Se realizaron medidas de sensibilidad y especificidad con las dinámicas restantes para comparar el diagnostico matemático con el diagnóstico clínico. Resultados: Los espacios de ocupación de los atractores cardiacos diferencian dinámicas cardiacas normales de dinámicas con enfermedad crónica y aguda, detectando además dinámicas patológicas con valores superiores a los límites de normalidad, logrando valores de sensibilidad de 0,937 y especificidad del 1. Conclusión: se estableció una nueva metodología de evaluación de la dinámica cardiaca de utilidad para el seguimiento clínico en pacientes de UCI.

ABSTRACT Introduction: The chaotic behavior of normal and acute cardiac dynamics has been characterized in the context of theory of dynamical systems and fractal geometry. Objective: to establish a new diagnostic method for assessing cardiac dynamics in ICU patients, for 16 hours. Methodology: This is a study in post-surgical patients admitted to intensive care (ICU) and in healthy subjects, taking a total of 47 continuous electrocardiographic recordings and/ or Holter, normal and acute pathology, evaluated in 16 hours. Induction with two normal and three UCI dynamics was developed; from the maximum and minimum values of the heart/time and total frequency of beats/minute for 16 hours recorded attractors they were constructed to assess their areas of occupation and fractal dimension, in order to establish differences and equalities regarding normal states and pathological. Sensitivity and specificity measurements were performed with the remaining dynamic to compare mathematical diagnosis with clinical diagnosis. Results: Space occupancy heart attractors differ dynamic normal cardiac dynamics with chronic and acute illness, in addition detecting dynamic pathological with above normal limits values, achieving sensitivity values of 0.937 and specificity of 1. Conclusion: a new methodology for evaluating cardiac dynamics useful for clinical monitoring in ICU patients was established.

Method validation of nanoparticle tracking analysis to measure pulmonary nanoparticle content: the size distribution in exhaled breath condensate depends on occupational exposure.

A particle exposure assessment based on the dose deposited in the lungs would be the gold standard for the evaluation of any resulting health effects. Measuring particles in exhaled breath condensate (EBC)-a matrix containing water and airway lining fluid-could help to evaluate particle retention in the lungs. This study aimed to (1) validate a nanoparticle tracking analysis (NTA) method for determining the particle number concentration and their hydrodynamic size distribution in EBC, and (2) apply this method to EBC collected from workers exposed to soapstone (n = 55) or quartz dust (n = 12) and controls (n = 11). A standard latex bead solution was used to determine the linear range, limit of detection (LOD), repeatability (coefficient of variation, CV), and bias in spiked EBC. An LM10 NanoSight instrument with NTA version 3.1 software was used for measurement. RTubes® were used for field collection of EBC. The repeatability obtained for a D50 size distribution in EBC showed less than 8% variability, with a bias <7%. The particle concentration was linear in the range ≤2.5 × 108 particles ml-1 with a LOD of 4 × 106 particles ml-1. A recovery of 117 ± 20% at 6.2 × 107 particles ml-1 was obtained with a CV <10% and a bias <20%. EBC from workers exposed to quartz, who experienced the largest exposure to silica particles, consistently exhibited a statistically significant (p < 0.01) higher concentration of particles in their EBC, with a size distribution shift towards larger values than the other groups. Results showed that the NTA technique performed well for characterizing the size distribution and concentrations of particles in EBC. The technique needs to be corroborated with a larger population of workers.

Urinary Clara Cell Protein in Kidney Transplant Patients: A Preliminary Study.

OBJECTIVE: The aim of this exploratory study was to analyze the urinary excretion of Clara cell protein (CC16), a new marker of proximal tubular dysfunction (PTD), in kidney transplantation (KT). MATERIALS AND METHODS: Urinary concentrations of CC16, ß2-microglobulin (ß2m), and N-acetyl-glucosaminidase (NAG) were measured in 50 KT patients (72% men; mean age 50.4 ± 12.4 years; diabetes in 24%; duration of KT 4.3 ± 3.1 years) and 10 healthy controls (6 men; mean age 33.6 ± 13.4 years). RESULTS: Urinary levels of ß2m, NAG, and CC16 were significantly higher in KT patients than in controls: ß2m: 0.77 (interquartile range [IQ] 0.22 to 4.62) g/g vs 0.069 (IQ 0.05 to 0.10) g/g; NAG: 3.16 (IQ 2.09 to 5.33) U/g vs 1.73 (IQ 1.25 to 2.07) U/g; CC16: 26.01 (IQ 8.62 to 123.3) g/g vs 2.51 (IQ 0.83 to 7.18) g/g (P < .001). Elevated levels of ß2m, NAG, and CC16 were found in 81%, 28%, and 71% of KT patients, respectively. Urinary levels of ß2m, NAG, and CC16 significantly increase as glomerular filtration rate (GFR) decreases. Interestingly, in patients with GFR >60 mL/min, we still found high levels of ß2m, NAG, and CC16 in 77%, 13%, and 52%, respectively. Diabetic subjects had significant higher levels of the 3 markers compared with nondiabetic subjects, without differences in albumin excretion or GFR. CC16 showed a positive correlation with urinary albumin (r = 0.42, P < .001), NAG (r = 0.352, P < .05), and ß2m (r = 0.75, P < .001). CONCLUSION: PTD is highly prevalent in KT patients. This is the first study that analyzes CC16 in KT patients, showing that the urinary excretion of this protein is significantly increased in this population. Further studies are needed to examine the clinical value of CC16 in KT patients.

Current of interacting particles inside a channel of exponential cavities: Application of a modified Fick-Jacobs equation.

Recently a nonlinear Fick-Jacobs equation has been proposed for the description of transport and diffusion of particles interacting through a hard-core potential in tubes or channels of varying cross section [Suárez et al., Phys. Rev. E 91, 012135 (2015)]PLEEE81539-375510.1103/PhysRevE.91.012135. Here we focus on the analysis of the current and mobility when the channel is composed by a chain of asymmetric cavities and a force is applied in one or the opposite direction, for both interacting and noninteracting particles, and compare analytical and Monte Carlo simulation results. We consider a cavity with a shape given by exponential functions; the linear Fick-Jacobs equation for noninteracting particles can be exactly solved in this case. The results of the current difference (when a force is applied in opposite directions) are more accurate for the modified Fick-Jacobs equation for particles with hard-core interaction than for noninteracting ones.

Pathogenic Helicobacter pylori strains translocate DNA and activate TLR9 via the cancer-associated cag type IV secretion system.

Helicobacter pylori (H. pylori) is the strongest identified risk factor for gastric cancer, the third most common cause of cancer-related death worldwide. An H. pylori constituent that augments cancer risk is the strain-specific cag pathogenicity island, which encodes a type IV secretion system (T4SS) that translocates a pro-inflammatory and oncogenic protein, CagA, into epithelial cells. However, the majority of persons colonized with CagA+ H. pylori strains do not develop cancer, suggesting that other microbial effectors also have a role in carcinogenesis. Toll-like receptor 9 (TLR9) is an endosome bound, innate immune receptor that detects and responds to hypo-methylated CpG DNA motifs that are most commonly found in microbial genomes. High-expression tlr9 polymorphisms have been linked to the development of premalignant lesions in the stomach. We now demonstrate that levels of H. pylori-mediated TLR9 activation and expression are directly related to gastric cancer risk in human populations. Mechanistically, we show for the first time that the H. pylori cancer-associated cag T4SS is required for TLR9 activation and that H. pylori DNA is actively translocated by the cag T4SS to engage this host receptor. Activation of TLR9 occurs through a contact-dependent mechanism between pathogen and host, and involves transfer of microbial DNA that is both protected as well as exposed during transport. These results indicate that TLR9 activation via the cag island may modify the risk for malignancy within the context of H. pylori infection and provide an important framework for future studies investigating the microbial-epithelial interface in gastric carcinogenesis.

Nefrocalcinosis como complicación de hipercalcemia por ingesta excesiva de calcio en el embarazo

Antecedentes: La hipercalcemia durante el embarazo es un hallazgo raro. La exposición prolongada a los altos niveles de calcio puede llevar a calcificaciones en distintos órganos maternos y en el feto puede llevar a abortos espontáneos y mortinatos. Caso clínico: Paciente primípara, con gestación de 20+4 semanas, remitida por falla renal aguda e hipertensión arterial. Ella reportó ingesta excesiva de queso, leche y multivitamínicos. Con calcio de 9,2 mg/dL y relación BUN/Creatinina de 6,8 se diagnostica intoxicación alimentaria y nefrocalcinosis medular por alta ingesta de calcio. Al cuarto día de hospitalización presenta sangrado vaginal y debido a las condiciones de la madre se termina el embarazo. Posteriormente presenta una mejoría clínica significativa y se da de alta. Discusión: La relevancia de este caso es que la presencia de hipercalcemia en el embarazo y su no identificación, aumenta el riesgo de aborto, y de hipocalcemia neonatal, que a su vez puede causar muerte materna. En este cuadro se pueden presentar varias complicaciones, siendo una de las más frecuentes la nefrocalcinosis, identificada en este reporte. Conclusión: La ingesta de calcio excesiva en gestantes puede causar nefrocalcinosis. Es importante la educación para evitar ésta y otras complicaciones.

Background: Hypercalcemia during pregnancy is a strange finding. The long exposure to high calcium levels can take to calcifications in different maternal organs and it can lead to miscarriage and stillborn. Case presentation: A woman with 20+4 weeks' gestation, who was remitted because of an acute renal failure and hypertension. She reported excessive intake of cheese, milk and multivitaminics. With a calcium level of 9.2 mg/dL and BUN/Creatinine of 6.8, diagnosed with food poisoning and medullary nephrocalcinosis as a result of the high calcium intake. At the fourth day at the hospital she presented vaginal bleeding and due to the conditions of the mother the pregnancy was ended. Afterwards she presented a significant clinical improvement and she was discharged from the hospital. Discussion: The relevance of this case is that the presence of hypercalcemia during pregnancy and not identifying it elevates the risk of miscarriage and neonatal hypocalcemia, which can cause maternal death. In this aspect, many complications can develop, being one of the most important the nephrocalcinosis, identified in this report. Conclusion: The excessive calcium intake in pregnant women can cause nephrocalcinosis. It is important to educate them to avoid this and other complications.

Response to vaccination against rabies in dogs immunized during surgery or under the effect of immunomodulatory drugs

According to WHO the most effective way to reduce the incidence of annual human rabies, is through vaccination of dogs and cats, since 90% of human cases are due to bites mainly from canines infected with the virus. The level of protection of dogs vaccinated against rabies varies significantly between countries of the region. The objective of this study was to evaluate the humoral immune response against rabies, in dogs with some kind of "immune modulation" experimentally induced. Dogs were immunized with polyvalent (Group 1), monovalent (Group 2) vaccines, and immunized during surgical castration (Group 3), dogs treated with triamcinolone acetonide (steroids) during immunization (Group 4) or vaccinated simultaneously with a commercial immunostimulant (Group 5). The results indicate that in all cases, the majority of animals could exceed the minimum limit of antibodies to be protected according to the WHO (0.5UI / ml). However, significant differences (p <0.05) in the use of mono- or polyvalent vaccines, the use of corticosteroids at the time of immunization and vaccination during surgical castration was found.

Management of congenital midline nasofrontal masses: case report and review of literature.

Epidermoid cysts, dermoids, gliomas, and meningo-/encephaloceles are the most important differential diagnoses in congenital nasofrontal masses. Since they arise from an abnormal fusion during fetal development, intracranial extension of the lesion has to be ruled out radiologically before therapy. Dermoids are the most common entity. We report about a congenital epidermoid cyst of the glabella and nasion that had been growing over the last two years before presentation in a 24-year-old patient. We discuss radiological imaging and the different surgical approaches described in literature.

Transport of interacting particles in a chain of cavities: description through a modified Fick-Jacobs equation.

We study the transport process of interacting Brownian particles in a tube of varying cross section. To describe this process we introduce a modified Fick-Jacobs equation, considering particles that interact through a hard-core potential. We were able to solve the equation with numerical methods for the case of symmetric and asymmetric cavities. We focused in the concentration of particles along the direction of the tube. We also preformed Monte Carlo simulations to evaluate the accuracy of the results, obtaining good agreement between theory and simulations.

Mean-field approach for diffusion of interacting particles.

A nonlinear Fokker-Planck equation is obtained in the continuous limit of a one-dimensional lattice with an energy landscape of wells and barriers. Interaction is possible among particles in the same energy well. A parameter γ, related to the barrier's heights, is introduced. Its value is determinant for the functional dependence of the mobility and diffusion coefficient on particle concentration, but has no influence on the equilibrium solution. A relation between the mean-field potential and the microscopic interaction energy is derived. The results are illustrated with classical particles with interactions that reproduce fermion and boson statistics.

Automated Identification of Abnormal Adult EEGs.

The interpretation of electroencephalograms (EEGs) is a process that is still dependent on the subjective analysis of the examiners. Though interrater agreement on critical events such as seizures is high, it is much lower on subtler events (e.g., when there are benign variants). The process used by an expert to interpret an EEG is quite subjective and hard to replicate by machine. The performance of machine learning technology is far from human performance. We have been developing an interpretation system, AutoEEG, with a goal of exceeding human performance on this task. In this work, we are focusing on one of the early decisions made in this process - whether an EEG is normal or abnormal. We explore two baseline classification algorithms: k-Nearest Neighbor (kNN) and Random Forest Ensemble Learning (RF). A subset of the TUH EEG Corpus was used to evaluate performance. Principal Components Analysis (PCA) was used to reduce the dimensionality of the data. kNN achieved a 41.8% detection error rate while RF achieved an error rate of 31.7%. These error rates are significantly lower than those obtained by random guessing based on priors (49.5%). The majority of the errors were related to misclassification of normal EEGs.

Pharmacokinetic evaluation of different generic triclabendazole formulations in heifers.

AIMS: To assess the comparative drug systemic exposure of a reference (RF) and four test (Test I, Test II, Test III and Test IV) formulations of triclabendazole (TCBZ) in heifers. METHODS: Thirty Holstein heifers were randomly distributed into five groups (n=6 per group). Animals in the RF group received the reference formulation (Fasinex), and those in the other groups received different commercially available TCBZ formulations (Test I, Test II, Test III and Test IV). All treatments were orally administered at 12 mg/kg bodyweight. The concentrations of TCBZ metabolites in plasma between 0 and 168 hours after treatment were quantified by high-performance liquid chromatography (HPLC). RESULTS: Triclabendazole sulphoxide (TCBZ.SO) and TCBZ-sulphone (TCBZ.SO2) were the only analytes recovered in plasma. Only the Test I formulation did not differ from the RF for all pharmacokinetic parameters measured for either metabolite (p>0.8). The TCBZ.SO area under the concentration vs. time curve for Test II formulation (268.9 µg.h/mL) was lower, and for Test III (619.9 µg.h/mL) and Test IV (683.4 µg.h/mL) was higher, than the RF (418.1 µg.h/mL) (p<0.005). CONCLUSION: Based on the currently available bioequivalence criteria, the only test formulation under evaluation that could be considered equivalent to the RF was the Test I formulation, which demonstrated an equivalent systemic exposure for the active TCBZ.SO metabolite. This comparison of TCBZ pioneer and test formulations in cattle raises awareness of the need for further quality control for drug approval in the veterinary pharmaceutical field in many regions of the world.

Is "intra-operating room" thromboelastometry useful in liver transplantation? A case-control study in 303 patients.

Coagulation monitoring during liver transplantation (LT) is, even today, fundamental to reduce blood loss during surgery. Thromboelastometry (TEM) is a proven technique for controlling the various parameters that influence coagulation. However, there are no studies linking "intra-operating room" TEM (orTEM) with LT outcomes. We describe a case-control study in 303 liver graft recipients analyzing variables associated with operative complications and long-term LT outcomes. The results showed that orTEM reduced the use of blood products in patients with Model for End-Stage Liver Disease scores of ≥ 21, retransplantation, and high surgical difficulty and important intraoperative bleeding. In addition, results in survival and postoperative complications were better when orTEM was used. In conclusion, we confirm that use of orTEM is associated with less use of blood products and a lower rate of complications after LT.

Donor characteristics that are associated with survival in liver transplant recipients older than 70 years with grafts.

INTRODUCTION: The use of grafts from donors older than 70 years of age is increasing due to the decrease in the number of donors and the increase in waiting list patients. MATERIAL AND METHODS: We undertook a univariate and multivariate analysis of 980 adult recipients of whole liver grafts, 129 of them from donors aged 70 years or older. RESULTS: No differences were found in patient survival compared with recipients of younger grafts. There were no higher rates of rejection, vascular or biliary complications, postoperative bleeding, or infections, but older grafts were associated with graft dysfunction (P = .01) and a higher frequency of postoperative refractory ascites (P = .007), but without a greater need for retransplantation. As graft-associated factors, the joint presence in the donor of diabetes (P = .00; confidence interval [CI] = 0.04-0.117), hypertension (P = .00; CI = 0.22-0.39), and weight of more than 90 kg (P = .031; CI = 0.05-0.104) were suggestive of poor prognostic factors in recipient survival. Survival in hepatitis C virus (HCV) recipients or recipients aged older than 60 years was worse with donors aged older than 70 years, although not significantly so. With grafts from donors aged older than 80 years (n = 15), although patient survival rate was good (70% at 10 years), there was a higher rate of retransplantation (20%) and the early mortality rate was 13.3%. CONCLUSIONS: Use of grafts from donors aged older than 70 years is safe, with similar survival to patients with younger grafts. The appearance of initial dysfunction with prolonged ascites may be due to a delay in reaching a correct functionality, but was not associated with increased mortality, complications, or need for retransplantation. It should also be avoided in recipients older than 60 years or with HCV. Grafts older than 80 years were associated with a good long-term patient survival but at the expense of a higher rate of retransplantation. However, it helps to reduce the time on the waiting list and, thus, mortality. We noted decreased survival associated with donor hypertension, diabetes, and obesity, so these donors should be selected more rigorously.

Human papillomavirus genotypes in genital warts in Latin America: a cross-sectional study in Bogota, Colombia.

Epidemiological studies on benign lesions related to human papillomavirus (HPV) infection are scarce in Latin America. We enrolled 342 consecutive patients with lesions suspected of being genital warts (GW). All patients underwent confirmatory biopsy and GP5+/GP6+/- Reverse Line Blot HPV testing on frozen tissue. In 261 (81%) cases, the diagnosis was confirmed by histopathology and HPV was detected in 90.6% of men and 87.7% of women. HPV 6 was by far the most common type in both women (62%) and men (56%), followed by HPV 11 (∼20%). Co-infection with these two types occurred in 7% and 12% of women and men, respectively. HPV16 ranked third in prevalence, with 16% of patients testing positive. Twenty-five percent of cases tested positive for multiple HPV genotypes. Although HPV 6 and HPV 11 were the main types detected and no differences between men and women were observed, we found HPV 11 contributed more to GW aetiology compared with previous reports, showing a variability of HPV type distribution in GW across populations. This information is valuable baseline data in Latin America for future estimations of the burden of GW in men and women and shows the potential benefit obtainable by prophylactic vaccination against HPV types 6 and 11.