Transcriptome-Wide Prediction and Measurement of Combined Effects Induced by Chemical Mixture Exposure in Zebrafish Embryos.

BACKGROUND: Humans and environmental organisms are constantly exposed to complex mixtures of chemicals. Extending our knowledge about the combined effects of chemicals is thus essential for assessing the potential consequences of these exposures. In this context, comprehensive molecular readouts as retrieved by omics techniques are advancing our understanding of the diversity of effects upon chemical exposure. This is especially true for effects induced by chemical concentrations that do not instantaneously lead to mortality, as is commonly the case for environmental exposures. However, omics profiles induced by chemical exposures have rarely been systematically considered in mixture contexts. OBJECTIVES: In this study, we aimed to investigate the predictability of chemical mixture effects on the whole-transcriptome scale. METHODS: We predicted and measured the toxicogenomic effects of a synthetic mixture on zebrafish embryos. The mixture contained the compounds diuron, diclofenac, and naproxen. To predict concentration- and time-resolved whole-transcriptome responses to the mixture exposure, we adopted the mixture concept of concentration addition. Predictions were based on the transcriptome profiles obtained for the individual mixture components in a previous study. Finally, concentration- and time-resolved mixture exposures and subsequent toxicogenomic measurements were performed and the results were compared with the predictions. RESULTS: This comparison of the predictions with the observations showed that the concept of concentration addition provided reasonable estimates for the effects induced by the mixture exposure on the whole transcriptome. Although nonadditive effects were observed only occasionally, combined, that is, multicomponent-driven, effects were found for mixture components with anticipated similar, as well as dissimilar, modes of action. DISCUSSION: Overall, this study demonstrates that using a concentration- and time-resolved approach, the occurrence and size of combined effects of chemicals may be predicted at the whole-transcriptome scale. This allows improving effect assessment of mixture exposures on the molecular scale that might not only be of relevance in terms of risk assessment but also for pharmacological applications. https://doi.org/10.1289/EHP7773.

Characterisation and mapping of scattered radiation fields in interventional radiology theatres.

We used the Timepix3 hybrid pixel detector technology in order to determine the exposure of medical personnel to ionizing radiation in an interventional radiology room. We measured the energy spectra of the scattered radiation generated by the patient during X-ray image-guided interventional procedures. We performed measurements at different positions and heights within the theatre. We first observed a difference in fluence for each staff member. As expected, we found that the person closest to the X-ray tube is the most exposed while the least exposed staff member is positioned at the patient's feet. Additionally, we observed a shift in energy from head to toe for practitioners, clearly indicating a non-homogenous energy exposure. The photon counting Timepix3 detector provides a new tool for radiation field characterisation that is easier-to-use and more compact than conventional X-ray spectrometers. The spectral information is particularly valuable for optimising the use of radiation protection gear and improving dosimetry surveillance programs. We also found the device very useful for training purposes to provide awareness and understanding about radiation protection principles among interventional radiology staff.

Actualización en abuso de drogas por vía nasal / Update on drug abuse by nasal route

La vía nasal, ya sea mediante la inhalación o aspiración, se ha convertido en una ruta atractiva para quienes abusan de sustancias, principalmente por la fácil accesibilidad y la rápida absorción sistémica, además de evitar las consecuencias asociadas al uso de drogas intravenosas (enfermedades de transmisión). El objetivo de esta revisión es presentar una actualización de diversas sustancias que son utilizadas por esta vía, enfocándose en aquellas en las que se ha documentado daños en la anatomía nasal.

The nasal route, either by inhalation or aspiration, has become an attractive route for substances abusers, mainly because of its easy accessibility, rapid systemic absorption and also to avoid the consequences associated with intravenous drug use (transmitted diseases). The objective of this review is to present an update of various substances that are used by this route, focusing on those in which damage to the nasal anatomy has been documented.

Declines in prevalence of adolescent substance use disorders and delinquent behaviors in the USA: a unitary trend?

BACKGROUND: Downward trends in a number of adolescent risk behaviors including violence, crime, and drug use have been observed in the USA in recent years. It is unknown whether these are separate trends or whether they might relate to a general reduction in propensity to engage in such behaviors. Our objectives were to quantify trends in substance use disorders (SUDs) and delinquent behaviors over the 2003-2014 period and to determine whether they might reflect a single trend in an Externalizing-like trait. METHODS: We analyzed data from 12 to 17 year old participants from the National Survey on Drug Use and Health, a representative survey of the household dwelling population of the USA, across the 2003-2014 period (N = 210 599). Outcomes included past-year prevalence of six categories of substance use disorder and six categories of delinquent behavior. RESULTS: Trend analysis suggested a net decline of 49% in mean number of SUDs and a 34% decline in delinquent behaviors over the 12-year period. Item Response Theory models were consistent with the interpretation that declines in each set of outcomes could be attributed to changes in mean levels of a latent, Externalizing-like trait. CONCLUSIONS: Our findings suggest that declines in SUDs and some delinquent behaviors reflect a single trend related to an Externalizing-like trait. Identifying the factors contributing to this trend may facilitate continued improvement across a spectrum of adolescent risk behaviors.

Rinosporidiosis nasal: reporte de un nuevo caso y revisión de la literatura / Nasal rhinosporidiosis: new case report and review

La rinosporidiosis es una enfermedad granulomatosa rara producida por el microorganismo Rhinosporidium seeberi. A pesar de ser considerada una infección endémica en algunas zonas de Asia, en nuestro país es una enfermedad extremadamente rara. Se presenta el caso clínico de un escolar de 10 años que consulta por aumento de volumen en fosa nasal izquierda de 1 mes de evolución, de crecimiento progresivo, con epistaxis autolimitada, presentando al examen físico una lesión polipoídea, en la cual, no existiendo sospecha previa, se determinó mediante histopatología la presencia de rinosporidio-sis. Se discute la epidemiología de la enfermedad, sus mecanismos de diseminación, alternativas de tratamiento y principales complicaciones.

Rhinosporidiosis is a rare granulomatous disease produced by the microorganism Rhinosporidium seeberi. Despite being considered an endemic infection in some areas of Asia, in our country it is an extremely rare disease. We present the case of a 10 year-old boy who consult for increased volumen in the left nostril of 1 month evolution, with progressive growth, self-limited epistaxis, and a physical examination with a polypoid lesion, in which there were no prior suspicion, histopathology determined the presence of rhinosporidiosis. Epidemiology of the disease, its dissemination mechanisms, treatment options and major complications are discussed.

Patología unilateral de senos paranasales con compromiso predominante de un seno: Descripción de serie de casos / Unilateral paranasal sinus disease with predominant commitment of one sinus: Case series description

Introducción: El velamiento de una cavidad paranasal representa un desafío diagnóstico y puede ser causado por diversas patologías. El examen clínico generalmente es insuficiente para orientar la conducta siendo necesario un estudio completo que incluya endoscopía, imágenes e histología para lograr un diagnóstico definitivo. Objetivo: Describir la impresión clínica, imagenológica, quirúrgica e histológica de pacientes con patología unilateral de senos paranasales. Material y método: Serie retrospectiva de 32 pacientes con patología sinusal unilateral operados en Hospital Clínico de la Universidad de Chile entre 2012 y 2014. Se consideró como criterio de inclusión el compromiso predominante de un seno paranasal en el estudio imagenológico. Se describen las variables: síntoma principal, impresión diagnóstica; clínica, imagenológica, quirúrgica, seno comprometido, entre otras. Resultados: El síntoma principal más frecuente fue obstrucción nasal (56%). Los diagnósticos más frecuentes fueron: patología inflamatoria (84%): pólipo antrocoanal (31%), mucocele (22%) y bola fúngica (22%) y patología tumoral benigna: papiloma invertido (16%), siendo el seno maxilar el más afectado (90%). La impresión diagnóstica quirúrgica fue más precisa que la imagenológica en determinar el diagnóstico definitivo, aunque esta diferencia no alcanzó significancia estadística. Discusión: Patología compleja que requiere estudio completo incluyendo endoscopía. Las imágenes son el segundo pilar en el diagnóstico y deben solicitarse de acuerdo a los hallazgos. El diagnóstico quirúrgico provee una mayor precisión diagnóstica. Conclusiones: Se incluyen varias patologías bajo este concepto, la patología inflamatoria predomina pero se debe tener alto índice de sospecha dado la relativa frecuencia de patología tumoral.

Introduction: Paranasal sinus opacity represents a diagnostic challenge and can be caused by diverse pathologies. Clinical examination is generally insufficient to achieve a definitive diagnosis and it is necessary a complete study including endoscopy, imaging and histology. Aim: To describe clinical, radiographical, surgical and histological diagnostic impressions of patients with unilateral sinus disease. Material and method: 32 retrospective serie with unilateral sinus disease treated at Hospital Clínico de la Universidad de Chile, between 2012 and 2014. The predominant commitment of one sinus on the tomography was considered as inclusion criterion. Principal symtom, clinical, radiographical and surgical diagnostic impressions, committed sinus, among others variables were studied. Results: The most frequent symtom was nasal obstruction (56%). The most frequent diagnoses were: inflammatory disease (84%): antrochoanal polyp (31%), mucocele (22%) and fungus ball (22%) and benign tumor: inverted papilloma (16%). The maxillary sinus was affected in 90%. Surgical diagnostic impression was more precise than radiographical impression in determining the definitive diagnosis, although this difference did not reach statistics significance. Discussion: Unilateral sinus disease is a complex pathology that requires comprehensive study including endoscopy. Images are the second pillar in the diagnosis and should be requested according to the findings. Surgical diagnostic impression provides greater diagnostic presicion. Conclusions: Several pathologies are included under this concept, inflammatory disease prevails but it is necessary to have high index of suspicion in view of the relative frequency of tumour pathology.

Magnetic resonance imaging and laparoscopic management of an ovarian remnant in a bitch.

Ovarian remnant tissue was diagnosed in a 6-year-old female Pointer presented with a history of periodic signs of oestrus after ovariohysterectomy. The diagnosis was based on clinical gynaecological examination, vaginoscopy, vaginal cytology, analysis of serum progesterone concentration, and magnetic resonance imaging. The ovarian remnant tissue was approached in a minimally invasive manner via laparoscopy and resected with a vessel-sealing system. The oestrus signs disappeared within 14 days after laparoscopy.

Smoking cessation is associated with lower rates of mood/anxiety and alcohol use disorders.

BACKGROUND: The psychological outcomes that accompany smoking cessation are not yet conclusive but positive outcomes could help to persuade quitting. METHOD: We used data from the longitudinal National Epidemiological Study of Alcohol and Related Conditions. Logistic regression was used to examine associations between cigarette smoking reduction and Wave 2 status of addiction/mental health disorder among daily smokers at Wave 1, stratified by status of the diagnosis of interest at Wave 1. We adjusted for differences in baseline covariates between smokers with different levels of smoking reduction between Wave 1 and Wave 2 using propensity score regression adjustment. RESULTS: After adjusting for propensity scores and other mental health/addiction co-morbidities at Wave 2, among daily smokers who had current or lifetime history diagnosis of the outcome of interest at Wave 1, quitting by Wave 2 predicted a decreased risk of mood/anxiety disorder [adjusted odds ratio (aOR) 0.6, 95% confidence interval (CI) 0.4-0.9] and alcohol disorder (aOR 0.7, 95% CI 0.5-0.99) at Wave 2. Among daily smokers with no lifetime history diagnosis of the outcome of interest at Wave 1, quitting smoking by Wave 2 predicted a decreased risk of drug use disorder at Wave 2 (aOR 0.3, 95% CI 0.1-0.9). CONCLUSIONS: There is no support in our data for the concern that smoking cessation would result in smokers' increased risk of some mental disorders. To the contrary, our data suggest that smoking cessation is associated with risk reduction for mood/anxiety or alcohol use disorder, even among smokers who have had a pre-existing disorder.

Rinosinusitis maxilar crónica de origen dental / Chronic maxillary rhinosinusitis of dental origin

Introducción: La rinosinusitis maxilar de origen dental (RSMD) es una entidad reconocida con una incidencia cercana al 30%. Su diagnóstico puede pasar inadvertido, tanto en la clínica como en las imágenes, llevando a persistencia de sintomatología y fracaso de tratamiento. Objetivo: Describir la presentación clínica, diagnóstico y tratamiento de pacientes con rinosinusitis maxilar de origen dental. Material y método: Reporte de casos. Se revisaron historias clínicas, imágenes radiológicas, protocolos operatorios y cultivos microbiológicos de pacientes con diagnóstico de rinosinusitis de origen dental atendidos en Clínica Las Condes. Resultados: Diez pacientes, siete mujeres y tres hombres con edad promedio de 63 años. Descarga posterior y rinorrea fueron los síntomas más frecuentes. El estudio incluyó radiografía dental y tomografía computarizada de cavidades paranasales. Las complicaciones secundarias a extracciones dentales y de implantes dentales fueron las etiologías más frecuentes, siendo el primer molar la pieza dental más comprometida. Todos los casos fueron manejados en conjunto por equipo médico y odontológico. Ocho pacientes requirieron tratamiento quirúrgico y 5 de ellos además procedimientos dentales asociados. La flora responsable fue mixta aerobia y anaerobia. Conclusión: En pacientes rebeldes a tratamiento y con síntomas unilaterales, se debe tener un alto índice de sospecha y buscar dirigidamente patologías dentales que expliquen cuadros rinosinusales máxilo-etmoidales.

Introduction: Odontogenic maxillary sinusitis is a well-recognized condition and accounts for approximately 30% of maxillary sinusitis cases. The diagnosis can be missed leading to failure in medical and surgical treatments. Aim: To describe clinical features, diagnosis procedures and treatment of odontogenic maxillary sinusitis. Material and method: Case Report. We retrospectively reviewed medical records, radiologic characteristic, surgical findings and intraoperative microbial cultures of patients with diagnosis of odontogenic sinusitis at Clínica Las Condes. Results: 10 patients were identified, 7 females and 3 males with a mean age of 63 years. Posterior discharge and rhinorrhea were the most common symptoms. Dental x-rays and paranasal sinus CT-scans were performed in all patients. Iatrogenic causes, which include dental implants and dental extractions, were the most common etiology and the 1st molar was the dental piece most frequently involved. Both otolaryngologists and dentistsworked together in all cases. 8 patients had endoscopic sinus surgery and five of them received concomitant management of the dental origin. Polymicrobial cultures were obtained. Conclusions: Otolaryngologists must have a high index of suspicion and look for an odontogenic cause in individuals with unilateral maxillary and ethmoidal symptoms, resistant to conventional sinusitis therapy.

Novel metabolites in cyanobacterium Cylindrospermopsis raciborskii with potencies to inhibit gap junctional intercellular communication.

Despite intensive research into toxic bloom-forming cyanobacteria, the majority of their metabolites remain unknown. The present study explored in detail a novel bioactivity identified in cyanobacteria, i.e. inhibition of gap junctional intercellular communication (GJIC), a marker of tumor promotion. The extracellular mixture (exudate) of the cyanobacterial strain Cylindrospermopsis raciborskii (SAG 1.97) was fractionated by semi-preparative reversed phase HPLC, and the fractions assessed for their potencies to inhibit GJIC. Two non-polar fractions that significantly inhibited GJIC were further fractionated, tested and analyzed using multiple mass spectrometric methods. Investigations led to the identification of a putative chemical compound (molecular formula C18H34O3, m/z 299.2581 for the [M+H](+) ion) responsible for observed bioactivities. Specific inhibitors of signaling pathways were used to screen for biochemical mechanisms beyond GJIC inhibition, and the results indicate the involvement of ERK1/2 kinases via a mechanism related to the action of epidermal growth factor EGF but clearly distinct from other anthropogenic tumor promoters like polychlorinated biphenyls or polycyclic aromatic hydrocarbons. The chemical and in vitro toxicological characterizations of the newly described metabolite provide important insights into the still poorly understood health impacts of complex toxic cyanobacterial blooms and indicate that currently applied monitoring practices may underestimate actual risks.

Programa de screening auditivo neonatal universal: experiencia de más de 10 años / Universal newborn hearing screening program: experience over 10 years

Introducción: La implementación de Programas de Evaluación Auditiva Neonatal (PEAN) eficientes permite mejorar la pesquisa de recién nacidos (RN) con hipoacusia congénita (HC), facilitando una intervención temprana. Objetivo: Describir los resultados del PEAN universal llevado a cabo por el Departamento de Otorrinolaringología de Clínica Las Condes. Material y método: Estudio descriptivo, retrospectivo. Se estudiaron los resultados del programa y las variables: género, edad de diagnóstico, edad gestational al parto y factores de riesgo asociados al desarrollo de HC en RN evaluados entre mayo 2001 y junio 2012. Resultados: Fueron evaluados 18.224 RN. Reprobaron esta evaluación 809 RN (4,43%). Se diagnostican 70 HC (56% varones, 44% mujeres), con una incidencia general estimada de 3-4 cada 1.000 RN en este establecimiento. 54,3% correspondió a HC unilaterales y 45,7% a bilaterales, siendo éstas en 90% leves a moderadas. El factor de riesgo mayormente asociado fue presencia de anomalías craneofaciales en 38,5% seguido de un peso nacimiento <1.500 gr. en 10%. Discusión y conclusiones: Es imperativo la realización de PEAN universales para diagnosticar a la población general susceptible a desarrollar HC y más aún en aquellas poblaciones donde se concentran los factores de riesgo.

Introduction: Efficient universal newborn hearing screening program (UNHSP) Implementation allows the inquest improvement of newborns with congenital hearing loss (CHL), facilitating an early intervention. Aim: To describe the results of the UNHSP carried out by the Department of Otorhinolaryngology of Clinica Las Condes. Material and method: Descriptive, retrospective study. We studied the program results and variables: sex, diagnosis age, birth age in weeks and risk factors associated with development CHL in newborns evaluated between May, 2001 and June, 2012. Results: 18.224 newborns were evaluated. 809 reproved this evaluation (4.43%). We diagnosed 70 CHL (56% males, 44% women), with an incidence estimated of 3-4 cases every 1.000 newborns. 54.3% corresponded to unilateral CHL and 45.7% bilateral, 90% of this CHL were slight to moderate. The presence of craniofacial anomalies was the main associate risk factor in 38,5% followed by a weight birth <1.500 gr. in a 10%. Discussion and conclusions: Is imperative the accomplishment of UNHSP to diagnose the population at risk of developing CHL and even more in those populations where the risk factors are concentrated.

Estrategias para mejorar el seguimiento del Programa de Evaluación Auditiva Neonatal Universal / Strategies to improve follow-up of the Universal Newborn Hearing Screening Program

Introducción: El Programa de Evaluación Auditiva Neonatal (PEAN) en Clínica Las Condes se inició el 2001 y ha evaluado más de 18.000 niños. Nuestro desafío actual es lograr que aquellos cuyo examen se encuentre alterado reciban precozmente evaluación y derivación oportuna. Objetivo: Analizar el impacto de estrategias para mejorar el seguimiento del programa por medio de la reducción del porcentaje de pérdida de seguimiento. Material y método: Durante 2010 se implementaron nueve estrategias para mejorar el seguimiento del PEAN. Mediante una cohorte retrospectiva se evaluaron los resultados de PEAN 12 meses previos y posteriores a la implementación de éstas. Resultados: El 2009 se evaluaron 1.797 niños, completaron el protocolo 71,1%, perdiéndose en el seguimiento 28,9%. El 2011, posterior a la implementación de las medidas, se evaluaron 1.823 niños, completaron el protocolo 85,1%, perdiéndose en el seguimiento sólo 14,9%. La diferencia del porcentaje de pérdidas de seguimiento entre el2009y 2011 fue de 13.87% (p: 0.042). Discusión y conclusiones: Es necesario descubrir las causas de pérdida de seguimiento para establecer estrategias que ayuden a mejorar estas cifras y permitir que todo niño pesquisado sea diagnosticado a tiempo. La implementación de estrategias como las planteadas en este trabajo son una forma práctica y efectiva para mejorar el seguimiento del PEAN.

Introduction: The Newborn Hearing Screening Program (NHSP) at Clinica Las Condes began in 2001 and up to date, has evaluated over 18.000 children. Our current challenge is to achieve that children with referred screening, receive early evaluation and intervention. Aim: To analyze the Impact of strategies to Improve program's follow-up reducing the percentage of follow-up losses. Material and method: During 2010 nine NHSP strategies were implemented to improve the follow-up. By a retrospective cohort NHSP's results were evaluated 12 months previous and after the implementation of these strategies. Results: In 20091.797 children were evaluated, 71,1% completed the protocol, with 28,9% lost in the follow-up. In 2011, after strategies' implementation, 1.823 children were evaluated, 85,1 %, completed the protocol and only 14,9 % were lost in the follow-up. The difference in the percentage lost between 2009 and 2011 was 13.87 % (p: 0.042). Discussion and conclusions: It is necessary to discover the reasons of loss to follow-up, in order to establish strategies that may allow every referred child to be diagnosed in time. Implementation of strategies like the raised in this investigation is a practical and effective way to improve the follow-up of NHSP.

Recirculación en rinosinusitis maxilar / Mucus recirculation in maxillary rhinosinusitis

Introducción: La recirculación de moco entre el ostium natural del seno maxilar y otras aberturas en el seno, altera el transporte mucociliar normal, favorece su acumula-ción y sobreinfección, perpetuando el fenómeno inflamatorio. Objetivo: Describir nuestra experiencia en el diagnóstico y tratamiento de pacientes con rinosinusitis maxilar crónica y/o aguda recurrente cuyo estudio reveló recirculación maxilar. Material y método: Estudio retrospectivo descriptivo. Se revisaron historias clínicas, nasofibroscopías, informes radiológicos y hallazgos operatorios. Resultados: Ocho pacientes con edad promedio de 43 años. El 100%% presentó antecedente de cirugía que involucraba el seno maxilar. Todos se presentaron como rinosinusitis maxilar crónica y/o aguda con reagudizaciones frecuentes (3 episodios/ año). El diagnóstico se realizó mediante nasofibroscopía que evidenció recirculación de moco entre ostium natural y accesorio. Cinco pacientes se sometieron a cirugía endoscópica para unir el ostium accesorio (OA) al natural, disminuyendo el número de exacerbaciones. Conclusión: La recirculación maxilar se debe sospechar en pacientes con diagnóstico de rinosinusitis maxilar crónica y/o aguda recurrente con antecedente de cirugías que involucren el seno maxilar. Su diagnóstico se basa en la observación de recirculación de moco a la nasofibroscopía. El manejo es quirúrgico y dependerá de la ubicación del OA y de la permeabilidad del ostium natural.

Introduction: Recirculation of mucus between the maxillary sinus natural ostium and adjacent openings disturbs mucociliary clearence leading to secretions accumulation and persistent infection, perpetuating the inflammatory phenomenon. Aim: Describe our experience in the diagnosis and treatment ofpatients with maxillary rhinosinusitis (chronic or acute recurrent) and maxillary recirculation. Material and method: Descriptive and retrospective study. Clinical records, radiologic characteristic, nasal endoscopies and surgical findings were reviewed. Results: 8 patients, mean age of 43 years. All of them had prior history of maxillary sinus surgery. Clinical presentation was maxillary rhinosinusitis, chronic or acute, with frequent episodes ofreagudization (3 episodes/year). The diagnosis was made by endoscopic nasal examination that showed mucus recirculation between natural and accessory ostium. Endoscopic sinus surgery was done in 5patients in order to communicate the accessory to the natural ostium, leading to a decrease in the number of exacerbations. Conclusions: Maxillary recirculation must be suspected in patients with maxillary rhinosinusitis (chronic or acute recurrent) who have had prior surgical procedures that involve the maxillary sinus. The diagnosis is based on the observation of the recirculation phenomenon in the nasal endoscopy. The treatment is surgical and depends on the location of the accessory ostium and the permeability of the natural ostium.

Treatment of spinal fractures using Lubra plates. A retrospective clinical and radiological evaluation of 15 cases.

The purpose of this retrospective study was to review the clinical use along with the short- and long-term outcome in patients treated with Lubra plates to stabilize spinal fracture and dislocations that were considered unstable at time of surgery according to the 'three compartment theory'. The data that were collected included breed, age, gender, body weight of the patients, cause of injury, neurological grade (pre- and postoperative), radiographic findings, surgical treatment, and clinical and radiological outcome. Thirteen dogs and two cats were included with thoracic (1 case), thoracolumbar (3 cases), midlumbar (5 cases) and caudal lumbar (6 cases) vertebral fractures. For stabilization, the small-sized (3 cases), medium-sized (6 cases), and large-sized (6 cases) Lubra plates were used. The clinical outcome was excellent in 10/15 patients, functional in 2/15 and poor in 3/15 with a median follow-up period of nine years (range 2 months to 12 years). The fractures eventually stabilized by ventral spondylosis. No implant failure was seen, however demineralization of the spinous processes necessitated implant removal in one case. Our results suggest that Lubra plating is an appropriate technique for thoracolumbar and lumbar vertebral fractures as well as luxations in dogs and cats. The prognosis for neurological recovery was excellent when the animal had a neurological grade of 3 and was not paralyzed.

[The embolisation of venous malformations]. / Die Rolle der Embolisation bei venösen Malformationen.

BACKGROUND: The treatment of congenital, vascular malformations is a challenge for physicians and patients. Although different therapeutic options have been described to date, their individual relevance has still to be defined.  METHODS: We performed a retrospective study of 61 patients with a venous malformation (VM, mean age 22  years), who were referred to our depart-ment during the last 5 years. The size of the VM was larger than 5  cm in 41 patients (66 %). The lower extremities were involved in 45  cases (73 %). The most frequent clinical manifestations were recurrent swelling (80 %), pain (63 %), varicosis (60 %) and thrombophlebitis (39 %). MR angiography with venous sequences was always performed before treatment. Depending on the localisation and the extension of the VM, different techniques of embolisation were selected: foam sclerotherapy or application of synthetic glue by direct punction, coiling of pelvic veins or arterial embolisation with glue. RESULTS: 42  patients (69 %) underwent a procedure because of the complaints or the extension of the VM. An embolisation was performed in 25  patients with 65  interventional sessions. The most frequent technique was foam sclerotherapy (45 ×), followed by glue injection (13 ×), pelvic -venous coiling (6 ×) and arterial embolisation with glue (1 ×). Fifteen patients (60 %) reported a very good and 8  patients a marked improvement (32 %). In two cases there was no change of the complaints. The postinterventional complications were severe pain (n = 3) and skin/fat necrosis at the toe of one patient. CONCLUSIONS: The embolisation of venous malformations is an effective therapeutic tool. Different techniques can be used to address specific localisations and morphological patterns. The com-plication rate is very low when a step-by-step -approach is used, so that a repeat intervention is feasible. However, a more specific documentation of the post-interventional changes of the VM is needed before a general recommendation can be given.

Chlorpyrifos and neurodevelopmental effects: a literature review and expert elicitation on research and policy

Organophosphate pesticides are widely used on food crops grown in the EU. While they have been banned from indoor use in the US for a decade due to adverse health effects, they are still the most prevalent pesticides in the EU, with Chlorpyrifos (CPF) being the most commonly applied. It has been suggested CPF affects neurodevelopment even at levels below toxicity guidelines. Younger individuals may be more susceptible than adults due to biological factors and exposure settings.

Shaping membranes for endocytosis.

Endocytosis is essential for virtually all eukaryotic cells to internalize nutrients, antigens, pathogens, and cell surface receptors from the plasma membrane into membrane-bounded, endocytic vesicles to regulate cell homeostasis, cell signaling, and development. Distinct mechanisms mediate endocytic uptake of a large variety of distinctly sized cargoes ranging from small molecules to viruses or bacteria. Common to all of these endocytic pathways is the deformation of the plasma membrane by intracellular factors including scaffolding proteins, amphipathic peripheral membrane proteins, and lipid-modifying enzymes. In this review we summarize how different cargoes exploit distinct pathways for cell entry, and how proteins assist the generation of curved membrane domains during internalization.

The agmatine-degrading enzyme agmatinase: a key to agmatine signaling in rat and human brain?

Agmatinase, an ureohydrolase belonging to the arginase family, is widely expressed in mammalian tissues including the brain. Here, it may serve two different functions, the inactivation of the arginine derivative agmatine, a putative neurotransmitter, and the formation of the diamine putrescine. In order to identify the cellular sources of agmatinase expression in the brain, we generated a polyclonal monospecific antibody against recombinant rat agmatinase. With immunocytochemistry, selected areas of rat and human brain were screened. Clearly, in both species agmatinase-like immunoreactivity was predominantly detected in distinct populations of neurons, especially cortical interneurons. Also, principal neurons in limbic regions like the habenula and in the cerebellum robustly expressed agmatinase protein. When comparing the overall agmatinase expression with immunocytochemical data available for agmatine and polyamine biosynthetic enzymes, the observed pattern may argue in favor of an agmatine inactivating function rather than fueling the alternative pathway of polyamine synthesis. The putative neurotransmitter agmatine is seemingly involved with mental disorders. Therefore, agmatinase may be similarly important for pathogenesis. The normal expression profile of the protein as described here may therefore be altered under pathological conditions.

Sequestration of manure-applied sulfadiazine residues in soils.

It is not the total but the (bio)accessible concentration of veterinary medicines that determines their toxicity in the environment. We elucidate the changes in (bio)accessibility of manure-applied sulfadiazine (SDZ) with increasing contact time in soil. Fattening pigs were medicated with 14C-labeled SDZ, and the contaminated manure (fresh and aged) was amended to 2 soil types (Cambisol, Luvisol) and incubated for 218 days at 10 degrees C in the dark. Antibiotic residues of different bioaccessibility were approached by sequential extractions with 0.01 M CaCl2 (CaCl2 fraction), methanol (MeOH fraction), and finally acetonitrile/water (residual fraction, microwave extraction at 150 degrees C). In each fraction, total radioactivity, SDZ, and its major metabolites were quantified. The results showed that both SDZ and,to a lesser extent 4-hydroxysulfadiazine (4-OH-SDZ) were rapidly reformed from N-acetylsulfadiazine (N-ac-SDZ) during the first 2-4 weeks after fresh manure application, i.e., the N-acetylated metabolite does not sequester in soil to a significant extent Yet, the water and methanol extractable SDZ and 4-OH-SDZ also dissipated rapidly (DT50 = 6.0-32 days) for the fresh manure treatment with similar rate constants for both soil types. In the residual fractions, however, the concentrations of both compounds increased with time. We conclude that the residual fraction comprises the sequestered pool of SDZ and its hydroxylated metabolite. There they are entrapped and may persist in soil for several years. Including the residual fraction into fate studies thus yields dissipation half-lives of SDZ which exceed those previously reported for sulfonamides by a factor of about 100.

Cellular and subcellular rat brain spermidine synthase expression patterns suggest region-specific roles for polyamines, including cerebellar pre-synaptic function.

In the brain, the polyamines spermidine (Spd) and spermine (Spm) serve highly specific functions by interacting with various ion channel receptors intimately involved with synaptic signaling. Both, glial cells and neurons contain Spd/Spm, but release and uptake mechanisms could re-distribute polyamines between cell types. The cellular and subcellular localization of polyamine biosynthetic enzymes may therefore offer a more appropriate tool to identify local sources of enhanced Spd/Spm synthesis, which may be related with specific roles in neuronal circuits and synaptic function. A recently characterized antibody against Spd synthase was therefore used to screen the rat brain for compartment-specific peaks in enzyme expression. The resulting labeling pattern indicated a clearly heterogeneous expression predominantly localized to neurons and neuropil. The highest levels of Spd synthase expression were detected in the accumbens nucleus, taenia tecta, cerebellar cortex, cerebral cortical layer I, hippocampus, hypothalamus, mesencephalic raphe nuclei, central and lateral amygdala, and the circumventricular organs. Besides a diffuse labeling of the neuropil in several brain areas, the distinct labeling of mossy fiber terminals in the cerebellar cortex directly indicated a synaptic role for Spd synthesis. Electron microscopy revealed a preferential distribution of the immunosignal in synaptic vesicle containing areas. A pre-synaptic localization was also observed in parallel and climbing fiber terminals. Electrophysiological recordings in acute cerebellar slices revealed a Spd-induced block of evoked extracellular field potentials resulting from mossy fiber stimulation in a dose-dependent manner.