Use of CTA Test Dose to Trigger a Low Cardiac Output Protocol Improves Acute Stroke CTP Data Analyzed with RAPID Software.

BACKGROUND AND PURPOSE: Contrast curve truncation in CTP protocols may introduce errors. We sought to identify risk factors and design a protocol to avoid truncation while limiting radiation. MATERIALS AND METHODS: In an initial fixed-timing cohort, patients underwent a 65-second CTP with 2-second delay postcontrast injection. Multivariable analysis identified factors associated with truncation. A later case-specific cohort underwent either the original protocol or a low cardiac output protocol with a 7-second delay and 75-second scanning window, with selection determined by CTA test-dose enhancement upswing delay. Time-density curves were assessed for truncation and compared between the 2 groups, and the radiation dose was evaluated. RESULTS: From September 2017 through May 2018, one hundred fifty-three patients underwent the standard fixed-timing protocol. Age (OR, 1.82/10-year increase; P = .019), reduced left ventricle ejection fraction (OR, 9.23; P = .001), and hypertension (OR, 0.32; P = .06) were independently associated with truncation in an exploratory multivariable model. From May 2018 through April 2019, one hundred fifty-seven patients underwent either the standard (72 patients) or low cardiac output protocol (85 patients). The fixed-timing cohort had 15 truncations (9.8%) versus 4 in the case-specific cohort (2.5%; P = .009). If the low cardiac output protocol were applied to those with >10.6% predicted risk of truncation based on age, left ventricle ejection fraction, and hypertension, the number of truncations would have decreased from 15 to 4 in the fixed-timing cohort. CONCLUSIONS: Older age, left ventricle ejection fraction, and the absence of hypertension increase the risk of time-density curve truncation. However, a CTA test-dose-directed case-specific protocol can reduce truncation to ensure accurate data while mitigating radiation dose increases.

Hydro-climatic changes of wetlandscapes across the world.

Assessments of ecosystem service and function losses of wetlandscapes (i.e., wetlands and their hydrological catchments) suffer from knowledge gaps regarding impacts of ongoing hydro-climatic change. This study investigates hydro-climatic changes during 1976-2015 in 25 wetlandscapes distributed across the world's tropical, arid, temperate and cold climate zones. Results show that the wetlandscapes were subject to precipitation (P) and temperature (T) changes consistent with mean changes over the world's land area. However, arid and cold wetlandscapes experienced higher T increases than their respective climate zone. Also, average P decreased in arid and cold wetlandscapes, contrarily to P of arid and cold climate zones, suggesting that these wetlandscapes are located in regions of elevated climate pressures. For most wetlandscapes with available runoff (R) data, the decreases were larger in R than in P, which was attributed to aggravation of climate change impacts by enhanced evapotranspiration losses, e.g. caused by land-use changes.

Encuesta de Percepción en Capacidad Instalada para la Formación de Médicos Residentes en Ortopedia (Traumatología) y Necesidades de la Atención en Patología Musculoesquelética Aguda y Crónica en México. Primera Parte / Installed Capacity Perception Survey for the Training of Resident's Program in Orthopedics and Care Needs in Acute and Chronic Musculoskeletal Pathology in Mexico

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Abstract: Introduction: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. Material and methods: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. Results: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients ˂ 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients ˃ 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. Conclusions: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and ˃ 90% without regular scientific production.

[Installed Capacity Perception Survey for the Training of Residents Program in Orthopedics and Care Needs in Acute and Chronic Musculoskeletal Pathology in Mexico]. / Encuesta de Percepción en Capacidad Instalada para la Formación de Médicos Residentes en Ortopedia (Traumatología) y Necesidades de la Atención en Patología Musculoesquelética Aguda y Crónica en México. Primera Parte.

INTRODUCTION: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. MATERIAL AND METHODS: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. RESULTS: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. CONCLUSIONS: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and 90% without regular scientific production.

INTRODUCCIÓN: Es fundamental que los médicos residentes de ortopedia (traumatología) sean altamente competentes en todos los aspectos, considerando el equilibrio entre la oferta, demanda, necesidad y contexto. Es primordial identificar la capacidad y calidad instalada para su formación en México. MATERIAL Y MÉTODOS: Estudio observacional, transversal, muestreo no probabilístico-conglomerados, en dos fases. El instrumento tiene ocho dominios, 57 variables y 4,867 ítems. Sesenta profesores de postgrado de 20 estados, 50 sedes hospitalarias, 22 programas universitarios. RESULTADOS: 1,038 años de experiencia (inteligencia colectiva), 17 años de experiencia/profesor (01 a 50 años). Se identificó: patología aguda 30 (2 a 90%), patología crónica 30 (5 a 96%), pacientes 15 años, 10 (3 a 30%), pacientes entre 15 y 65 años, 47 (2 a 78%), pacientes 65 años, 20 (2 a 60%), número de camas/sede 20 (2 a 510), número de consultorios 3 (1 a 48), el número de procedimientos quirúrgicos/sede al año a nivel nacional fue de 960 (50 a 24,650). La media nacional por médico residente es de 362 cirugías/año con 1,450 momentos quirúrgicos/año. CONCLUSIONES: Las necesidades y recursos para la formación de médicos especialistas en ortopedia/traumatología son en alto grado heterogéneos, por lo cual se debería adaptar a las necesidades epidemiológicas de la región de influencia, en un ámbito de transición epidemiológica. Sesenta y dos punto dos por ciento expresó no tener o tener deficiente infraestructura académica y científica en su sede, más de 50% sin rotación al extranjero y 90% sin producción científica regular.

Reaching a Vapor Sensitivity of 0.01 Parts Per Quadrillion in the Screening of Large Volume Freight.

The feasibility of detecting explosives in the atmosphere at concentrations as low as 0.01 ppq hinges on the poorly known question of what interfering species exist at these or higher concentrations. To clarify the issue, hundreds of samples of ambient air, either clean or loaded with explosives (from lightly contaminated environments) have been collected in fiberglass/stainless steel filters coated with Tenax-GR, thermally desorbed at variable temperature, and ionized with Cl- via secondary electrospray (SESI). They are analyzed with a narrow-band mobility filter (SEADM's P5 DMA) and a triple quadrupole mass spectrometer (Sciex's 5500), configured in series to transmit precursor and fragment ions of the explosives Nitroglycerin, PETN, RDX, and TNT. Blanks were sampled outdoors at a rural site (Boecillo, Valladolid, Spain), and loads were sampled at diverse locations. For RDX and TNT, atmospheric background inhibits detection below 1 part/trillion (ppt) without mobility filtering. This interference was drastically reduced by the DMA, allowing detection up to 1 part/quadrillion (ppq). Further sensitivity increase was achieved by scanning over a mobility region several percent around that of the target explosive, to separate various isobaric compounds by Gaussian deconvolution. (i) All four MS/MS channels analyzed exhibit several background peaks within the narrow mobility intervals investigated. At least one of these interferents is much stronger than the instrument background at the explosive's mobility, making DMA separation most helpful. (ii) For Nitroglycerin and PETN the combined filtering techniques have not lowered ambient chemical noise down to 0.01 ppq. (iii) Interferents are greatly reduced for TNT and RDX, resulting in minimal chemical noise: 322 blank tests for RDX yielded mean signal of 0.0012 ppq and standard deviation σ = 0.0035 ppq (mean + 3σ detection limit of 0.01 ppq).

Repellency of the Components of the Essential Oil, Citronella, to Triatoma rubida, Triatoma protracta, and Triatoma recurva (Hemiptera: Reduviidae: Triatominae).

The kissing bugs--Triatoma rubida (Uhler), Triatoma protracta (Uhler), and Triatoma recurva (Stal)--are common hematophagous bugs in southeastern Arizona and responsible for severe allergic reactions in some individuals who are bitten. They also possess the potential to transmit the blood parasite, Trypanosoma cruzi. We previously found the essential oil, citronella, to be an excellent deterrent of feeding of T. rubida on a restrained mouse. In this work, we tested major components--alcohols, aldehydes, and monoterpenes--of citronella oil for repellency against the three common triatome species endemic in southern Arizona. The following citronella oil components--geraniol, citronellol, limonene, and citronellal--in different concentrations and combinations were tested. All components of citronella oil demonstrated some inhibition of feeding, ranging from very weak inhibition (limonene) to significant inhibition (geraniol and citronellol). A mixture of geraniol and citronellol was found to be repellant at concentrations of .165 and .165 vol%, respectively, for all three triatome species. Citronellal and limonene had no significant repellent activity. The repellent activity of citronella oil appears to be acting through direct contact with the bugs rather than diffusion of vapors.

Glutaredoxin 2a overexpression in macrophages promotes mitochondrial dysfunction but has little or no effect on atherogenesis in LDL-receptor null mice.

AIMS: Reactive oxygen species (ROS)-mediated formation of mixed disulfides between critical cysteine residues in proteins and glutathione, a process referred to as protein S-glutathionylation, can lead to loss of enzymatic activity and protein degradation. Since mitochondria are a major source of ROS and a number of their proteins are susceptible to protein-S-glutathionylation, we examined if overexpression of mitochondrial thioltranferase glutaredoxin 2a (Grx2a) in macrophages of dyslipidemic atherosclerosis-prone mice would prevent mitochondrial dysfunction and protect against atherosclerotic lesion formation. METHODS AND RESULTS: We generated transgenic Grx2aMac(LDLR-/-) mice, which overexpress Grx2a as an EGFP fusion protein under the control of the macrophage-specific CD68 promoter. Transgenic mice and wild type siblings were fed a high fat diet for 14 weeks at which time we assessed mitochondrial bioenergetic function in peritoneal macrophages and atherosclerotic lesion formation. Flow cytometry and Western blot analysis demonstrated transgene expression in blood monocytes and peritoneal macrophages isolated from Grx2aMac(LDLR-/-) mice, and fluorescence confocal microscopy studies confirmed that Grx2a expression was restricted to the mitochondria of monocytic cells. Live-cell bioenergetic measurements revealed impaired mitochondrial ATP turnover in macrophages isolated from Grx2aMac(LDLR-/-) mice compared to macrophages isolated from non-transgenic mice. However, despite impaired mitochondrial function in macrophages of Grx2aMac(LDLR-/-) mice, we observed no significant difference in the severity of atherosclerosis between wildtype and Grx2aMac(LDLR-/-) mice. CONCLUSION: Our findings suggest that increasing Grx2a activity in macrophage mitochondria disrupts mitochondrial respiration and ATP production, but without affecting the proatherogenic potential of macrophages. Our data suggest that macrophages are resistant against moderate mitochondrial dysfunction and rely on alternative pathways for ATP synthesis to support the energetic requirements.

A Golgi study of the plasticity of dendritic spines in the hypothalamic ventromedial nucleus during the estrous cycle of female rats.

Estradiol-induced plasticity involves changes in dendritic spine density and in the relative proportions of the different dendritic spine types that influence neurons and neural circuits. Such events affect brain structures that control the timing of neuroendocrine and behavioral processes, influencing both reproductive and cognitive functions during the estrous cycle. Accordingly, to investigate the dendritic spine-related plastic changes that may affect the neural processes involved in mating, estradiol-mediated dendritic spine plasticity was studied in type II cells situated in the ventrolateral portion of the ventromedial hypothalamic nucleus (VMN) of female, adult rats. The rats were assigned to four different groups (n=6) in function of their stage in the estrous cycle: proestrus, estrus, metaestrus, and diestrus. Dendritic spine density and the proportions of the different spine types on type II neurons were analyzed in the ventrolateral region of the VMN of these animals. Dendritic spine density on primary dendrites of VMN type II neurons was significantly lower in metaestrus than in diestrus, proestrus and estrus (with no differences between these latter stages). However, a significant variation in the proportional density of the different spine types was found, with a higher proportion of thin spines in diestrus, proestrus and estrus than in metaestrus. Likewise, a higher proportion of mushroom spines was seen in diestrus and proestrus than in metaestrus, and a higher proportion of stubby spines in estrus than in diestrus and metaestrus. Very few branched spines were found during proestrus and they were not detected during estrus or metaestrus. The different types of dendritic spines in non-projection neurons of the VMN could serve to maintain greater synaptic excitatory activity when receptivity and estradiol levels are maximal. However, they may also fulfill an additional functional role when receptivity and estradiol decline. To date specific roles of the different types of spines in neural hypothalamic activity during the estrous cycle remain unknown and they clearly deserve further study.

[Perceived quality in hospitals of the Andalusia Healthcare System. The case of neurosurgery departments]. / Calidad percibida en hospitales del Servicio Sanitario Andaluz. El caso de los servicios de neurocirugía.

OBJECTIVE: To analyse the characteristics of the perceived quality in hospitals of the Andalusia healthcare system and compare this with that in Andalusian Neurosurgery departments. MATERIAL AND METHODS: Randomised surveys, adjusted for working age, were performed in Andalusia using a telephone questionnaire based on the SERVQUAL model with the appropriate modification, with the subsequent selection of a subgroup associated with neurosurgery. Perceived quality was classified as; technical, functional and infrastructure quality. RESULTS: The overall satisfaction was 76.3%. Frequency analysis found that variables related to the technical quality (good doctors, successful operations, trained staff, etc.) obtained more favourable outcomes. Those related to time (wait, consulting, organizing schedules) obtained worse outcomes. The care of families variables obtained poor results. There was no difference between the overall Andalusian healthcare system and neurosurgery departments. In the mean analysis, women and older people gave more favourable responses, especially for variables related to infrastructure quality. In the "cluster" analysis, there were more favourable responses by elderly people, with no differences in gender (P<.009). CONCLUSIONS: There is no difference in perceived quality between the Andalusian healthcare system overall and neurosurgery departments. The perceived quality of the Andalusian healthcare system is higher in the elderly people. The analysis of perceived quality is useful for promoting projects to improve clinical management.

Calidad percibida en hospitales del Servicio Sanitario Andaluz. El caso de los servicios de neurocirugía / Perceived quality in hospitals of the Andalusia Healthcare System. The case of neurosurgery departments

Objetivo: Analizar las características de la calidad percibida de los usuarios del sistema público hospitalario de salud de Andalucía y compararla con las de los usuarios de los servicios de neurocirugía andaluces. Material y métodos: Encuestas aleatorizadas ajustadas por población activa en la comunidad andaluza mediante cuestionario telefónico basado en modelo SERVQUAL con modificación propia, y selección posterior de subgrupo relacionado con los servicios de neurocirugía. Se dividió la calidad percibida en calidad técnica, funcional y de infraestructuras. Resultados: La satisfacción general fue del 76,3%. Del análisis de frecuencias se observó que las variables relacionadas con la calidad técnica (buenos médicos, éxito en operaciones, personal preparado, etc.) obtuvieron resultados más favorables. Aquellas relacionadas con el tiempo (espera, en consulta, organización de horarios) obtuvieron resultados más desfavorables. Las variables de atención a familiares obtuvieron resultados desfavorables. No existieron diferencias entre el global de la sanidad andaluza y los servicios de neurocirugía. En el análisis de medias las mujeres y las personas de mayor edad presentaron respuestas más favorables, sobre todo para variables relacionadas con la calidad de infraestructuras. En el análisis de cluster se observó tendencia a respuestas más favorables conforme la edad era mayor sin predominio de género (p < 0,009). Conclusiones: No hay diferencias en la calidad percibida entre los servicios de neurocirugía y el resto de la sanidad. La calidad percibida en la sanidad andaluza es mayor conforme la edad del usuario es mayor. El análisis de calidad percibida es útil para plantear proyectos de mejora de la gestión clínica (AU)

Objective: To analyse the characteristics of the perceived quality in hospitals of the Andalusia healthcare system and compare this with that in Andalusian Neurosurgery departments. Material and methods:Randomised surveys, adjusted for working age, were performed in Andalusia using a telephone questionnaire based on the SERVQUAL model with the appropriate modification, with the subsequent selection of a subgroup associated with neurosurgery. Perceived quality was classified as; technical, functional and infrastructure quality. Results: The overall satisfaction was 76.3%. Frequency analysis found that variables related to the technical quality (good doctors, successful operations, trained staff, etc.) obtained more favourable outcomes. Those related to time (wait, consulting, organizing schedules) obtained worse outcomes. The care of families variables obtained poor results. There was no difference between the overall Andalusian healthcare system and neurosurgery departments. In the mean analysis, women and older people gave more favourable responses, especially for variables related to infrastructure quality. In the "cluster" analysis, there were more favourable responses by elderly people, with no differences in gender (P < .009). Conclusions: There is no difference in perceived quality between the Andalusian healthcare system overall and neurosurgery departments. The perceived quality of the Andalusian healthcare system is higher in the elderly people. The analysis of perceived quality is useful for promoting projects to improve clinical management (AU)

Method for outlier detection: a tool to assess the consistency between laboratory data and ultraviolet-visible absorbance spectra in wastewater samples.

Reliable estimations of the evolution of water quality parameters by using in situ technologies make it possible to follow the operation of a wastewater treatment plant (WWTP), as well as improving the understanding and control of the operation, especially in the detection of disturbances. However, ultraviolet (UV)-Vis sensors have to be calibrated by means of a local fingerprint laboratory reference concentration-value data-set. The detection of outliers in these data-sets is therefore important. This paper presents a method for detecting outliers in UV-Vis absorbances coupled to water quality reference laboratory concentrations for samples used for calibration purposes. Application to samples from the influent of the San Fernando WWTP (Medellín, Colombia) is shown. After the removal of outliers, improvements in the predictability of the influent concentrations using absorbance spectra were found.

Effects of selective estrogen receptor modulators on allocentric working memory performance and on dendritic spines in medial prefrontal cortex pyramidal neurons of ovariectomized rats.

Estradiol and some selective estrogen receptor modulators (SERMs) are neuroprotective in a variety of experimental models of neurodegeneration, reduce the inflammatory response of glial cells, reduce anxiety and depression, promote cognition and modulate synaptic plasticity in the hippocampus of rodents. In this study we have assessed whether estradiol and two SERMs currently used in clinics, tamoxifen and raloxifene, affect medial prefrontal cortex function and morphology. Rats were ovariectomized and six days later some animals received a subcutaneous injection of the estrogenic compounds. In a first experiment animals were treated with estradiol benzoate or sesame oil vehicle. In a second experiment animals received raloxifene, tamoxifen or dimethyl sulfoxide as vehicle. Twenty four hours after the pharmacological treatment, animals were challenged to solve an allocentric working memory paradigm in a "Y" maze. Twenty trials consisting of a study phase and a test phase were conducted according to a delayed match-to-sample procedure in a single one-day session. Animals that were not submitted to behavioral test were used for Golgi analysis of the prefrontal cortex. Rats treated with estradiol benzoate, tamoxifen or raloxifene performed better in the Y maze and showed a significant increase in the numerical density of dendritic spines in secondary apical dendrites of layer III pyramidal neurons from the prelimbic/infralimbic prefrontal cortex, compared to their respective control groups. These findings suggest that estradiol, tamoxifen and raloxifene improve prefrontal cortex-related cognitive performance and modulate prefrontal cortex morphology in ovariectomized rats.

SU-E-I-34: Air Kerma to Estimated Entrance Skin Dose Look-Up Tables: A Tool to Improve Dose Awareness in the Angiography Suite.

PURPOSE: Although air kerma (AK) is displayed during a case, often it does not represent the entrance skin dose (ESD), which can be estimated. The purpose of this work is to develop and provide system-customized AK-to- ESD look-up tables (LUTs) for immediate reference so that physicians can better evaluate the likelihood of deterministic skin reactions to weigh the risk-versus-benefit of continuing high-dose procedures. METHODS: Four correction factors are applied to estimate ESD from AK: inverse square correction from the interventional reference point to the average entrance table position, backscatter factor, mean energy absorption coefficient ratio, and measured table attenuation. Correction factors are room and service specific; therefore, room-specific AK-to-ESD LUTs are posted for easy reference. LUTs also list corresponding tissue reactions and their approximate time-of-onset. Protocols can be established for nurse or technology staff to provide verbal AK dose notifications during the case at crucial skin reaction dose thresholds (e.g. 2Gy indicating possible skin erythema and 5Gy indicating potentially prolonged recovery or permanent skin damage). Patient follow-up protocols can be established if the estimated ESD exceeds a set trigger level (e.g. 5Gy). Staff and physicians surveys evaluate usefulness and impact of dose awareness by system users. RESULTS: Two surveys report feedback on LUTs from physicians and technologists with 14 years median experience (range: 3-24 years). Over three-quarters of all angiography system users identify the LUTs and verbal dose notifications as positively affecting the institution's 'Patient First' initiative and roughly one-half of the imaging system users indicate that the LUTs and site-specific dose trigger level improves the dose awareness of care providers. CONCLUSIONS: Our efforts have focused on educating care providers about the differences between displayed AK and the estimated ESD. LUTs provide physicians and staff an immediate reference for estimated ESD and the associated deterministic skin effects at specific dose levels.

SU-E-I-50: The ACR CT Dose Index Registry: Implementation Challenges and Preliminary Data.

PURPOSE: To successfully register our institution into the American College of Ragiology (ACR) CT Dose Index Registry (DIR), to discuss the technical and implementation challenges of doing so, and to review preliminary results. METHODS: TRIAD is the American College of Radiology Imaging Network's (ACRIN) image acquisition and management software, with the purpose of receiving and then transmitting DICOM structured dose report files from institutional CT scanners around the country. TRIAD was installed onto a virtual machine server at our institution so that anonymized and encrypted DICOM structured dose report files from our 6 CT scanners could be sent to the TRIAD Application Server at ACR. Doing so required collaboration between ACR and IT, PACS personnel and the physicist on site. Implementation involved several challenges, such as software installation and data transmission consistency problems. Since numerous institutions are involved, the ACR required an exam mapping process via the Radlex playbook to unify the protocol classification. These challenges have been overcome and data is being successfully transmitted to and analyzed by the ACR. RESULTS: The first report comparing dose data (CTDI and DLP by examination and by scan) between our site and others around the region and country was made available recently. For each exam, the report includes boxplots and histogram data for a variety of standard protocols. For example, for a CT head exam, our median CTDIvol and DLP were 44 mGy and 736 mGy-cm compared with 64 mGy and 844 mGy-cm respectively, for all other facilities registered in the DIR. CONCLUSIONS: The ACR CT DIR registry is a useful tool for dose data mining and will eventually establish national benchmarks for CT dose indices. Our experience will allow others to anticipate these challenges and have potential solutions available for when they do arise.

Morphological development of dendritic spines on rat cerebellar Purkinje cells.

The posterior cerebellum is strongly involved in motor coordination and its maturation parallels the development of motor control. Climbing and mossy fibers from the spinal cord and inferior olivary complex, respectively, provide excitatory afferents to cerebellar Purkinje neurons. From post-natal day 19 climbing fibers form synapses with thorn-like spines located on the lower primary and secondary dendrites of Purkinje cells. By contrast, mossy fibers transmit synaptic information to Purkinje cells trans-synaptically through granule cells. This communication occurs via excitatory synapses between the parallel fibers of granule cells and spines on the upper dendritic branchlets of Purkinje neurons that are first evident at post-natal day 21. Dendritic spines influence the transmission of synaptic information through plastic changes in their distribution, density and geometric shape, which may be related to cerebellar maturation. Thus, spine density and shape was studied in the upper dendritic branchlets of rat Purkinje cells, at post-natal days 21, 30 and 90. At 90 days the number of thin, mushroom and thorn-like spines was greater than at 21 and 30 days, while the filopodia, stubby and wide spines diminished. Thin and mushroom spines are associated with increased synaptic strength, suggesting more efficient transmission of synaptic impulses than stubby or wide spines. Hence, the changes found suggest that the development of motor control may be closely linked to the distinct developmental patterns of dendritic spines on Purkinje cells, which has important implications for future studies of cerebellar dysfunctions.

Cytoarchitectural impairments in the medium spiny neurons of the Nucleus Accumbens core of hyperactive juvenile rats.

Dopaminergic activity in the Nucleus Accumbens has been strongly implicated in the motor hyperactivity associated with Attention deficit hyperactivity disorder. Dopaminergic and glutamatergic terminals converge on the dendritic spines of medium spiny neurons of the nucleus accumbens core, which modulate the excitatory glutamatergic activity. In this work, a Golgi study was carried out to investigate the effects of dopamine depletion on the cytoarchitecture of dendritic spines of nucleus accumbens core medium spiny neurons. The dopaminergic system of newborn male rats was lesioned intracisternally by using 6-hydroxydopamine, and subsequently, the motor activity, spine density, and the proportion of thin, stubby, mushroom, wide, branched, and double spines was compared to those in control and intact animals. Motor activity was significantly increased in the dopamine-depleted animals and while the spine density was reduced, there was no change in the proportion of the specific types of spines. Larger thin spines were observed in the dopamine-depleted animals. Indeed, dopamine depletion may lead to spine retraction due to the disregulation of spine development, and/or an increase in glutamatergic activity. The enlargement of thin spines may suggest a compensatory mechanism to increase the efficiency of synaptic inputs in response to a decrease in spines number. Together, the present findings suggest an alteration to the excitatory/inhibitory balance on dendritic spines of medium spiny neurons of the nucleus accumbens core in hyperactive juvenile rats following early dopamine depletion.

Damage and plasticity in adult rat hippocampal trisynaptic circuit neurons after neonatal exposure to glutamate excitotoxicity.

Hippocampal vulnerability to excitotoxicity has been widely studied along with its implication to learning and memory. Neonatal glutamate excitotoxicity induces loss of CA1 pyramidal neurons in adult rats concomitantly with some plastic changes in the dendritic spines of surviving neurons. At least in part, these may underlie the place learning impairments seen in previous studies based on a similar excitotoxicity-inducing model. In the present study, cytoarchitecture of dentate gyrus, CA3 and CA1 fields were evaluated in 120-day-old rats, after they had been neonatally treated with glutamate as monosodium salt. Dentate granule cells and CA1 pyramidal neurons were less than those counted in NaCl-treated control animals. In addition, dentate granule cells had more dendrites as well as more branched spines. Spine density in CA1 pyramidal neurons was greater than in the controls. Additionally, thin and mushroom spines were proportionally more abundant in monosodium glutamate-treated animals. No effects were seen in the hippocampal CA3 field. Our results strongly suggest a long-term induction of plastic changes in the cytoarchitecture of the hippocampal trisynaptic circuit neurons after cell death provoked by the monosodium glutamate-induced excitotoxicity. These plastic events as well as the aberrant expression of the glutamate NMDA receptors resulting from monosodium glutamate neonatal treatment could be strongly associated with the place learning impairments previously reported.

Invasion of human retinal vascular endothelial cells by Toxoplasma gondii tachyzoites.

BACKGROUND: Toxoplasma gondii infection is a leading cause of posterior uveitis. Human retinal endothelial cells (HREC) are more susceptible to infection with T gondii tachyzoites than other subpopulations of endothelial cells. It is hypothesised that this phenomenon reflects differences in invasion efficiency. METHODS: YFP-expressing RH strain T gondii tachyzoites were added to confluent HREC or human dermal endothelial cells (HDEC) (MOI = 50:1). Tachyzoite invasion after 1 h was determined by microplate reading of fluorescence intensity or parasite counts obtained using image analysis software. Selected cultures were incubated for three subsequent days, at which time fluorescence intensity indicated intracellular tachyzoite proliferation. RESULTS: HREC-tachyzoite cultures were more fluorescent than HDEC-tachyzoite cultures after 1 h (p = 0.020, paired t test, 3 experiments). Parasite counts also indicated that more tachyzoites invaded HREC than HDEC (p = 0.042, paired t test, 5 experiments). At 3 days, fluorescence intensity remained higher in HREC-tachyzoite cultures (p< or =0.002, t test, 3 experiments). CONCLUSION: In culture, T gondii tachyzoites invade HREC with greater efficiency than they invade HDEC. This observation suggests that the relative susceptibility of HREC to infection may reflect a high efficiency of tachyzoite invasion which may be relevant to understanding how T gondii infects human retina.

Photosensitizing properties of 6-methoxy-2-naphthylacetic acid, the major metabolite of the phototoxic non-steroidal anti-inflammatory and analgesic drug nabumetone.

The photobiological properties of 6-methoxy-2-naphthylacetic acid (6-MNAA) were studied using a variety of in vitro phototoxicity assays: photohemolysis, photoperoxidation of linoleic acid, photosensitized degradation of histidine and thymine and the Candida phototoxicity test. 6-MNAA was phototoxic in vitro. 6-MNAA reduced nitro blue tetrazolium (NBT) when irradiated with lambda > or = 300 nm in deoxygenated aqueous buffer solution (pH 7.4). NBT can be reduced by reaction with the excited state of 6-MNAA subject to interference with molecular oxygen. The photohemolysis rate was inhibited by the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO), sodium azide (NaN3) and reduced glutathione (GSH). Photoperoxidation of linoleic acid and photosensitized degradation of histidine and thymine were significantly inhibited by sodium azide and reduced glutathione. 6-MNAA was phototoxic to C. albicans, C. lipolytica and C. tropicalis. A mechanism involving singlet oxygen, radicals, and electron transfer reactions is suggested for the observed phototoxicity.