Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage.

BACKGROUND Perihematomal edema contributes to secondary brain injury in the course of intracerebral hemorrhage. The effect of decompressive surgery on perihematomal edema after intracerebral hemorrhage is unknown. This study analyzed the course of PHE in patients who were or were not treated with decompressive craniectomy. METHODS More than 100 computed tomography images from our published cohort of 25 patients were evaluated retrospectively at two university hospitals in Switzerland. Computed tomography scans covered the time from admission until day 100. Eleven patients were treated by decompressive craniectomy and 14 were treated conservatively. Absolute edema and hematoma volumes were assessed using 3-dimensional volumetric measurements. Relative edema volumes were calculated based on maximal hematoma volume. RESULTS Absolute perihematomal edema increased from 42.9 ml to 125.6 ml (192.8%) after 21 days in the decompressive craniectomy group, versus 50.4 ml to 67.2 ml (33.3%) in the control group (Δ at day 21 = 58.4 ml, p = 0.031). Peak edema developed on days 25 and 35 in patients with decompressive craniectomy and controls respectively, and it took about 60 days for the edema to decline to baseline in both groups. Eight patients (73%) in the decompressive craniectomy group and 6 patients (43%) in the control group had a good outcome (modified Rankin Scale score 0 to 4) at 6 months (P = 0.23). CONCLUSIONS Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift.

Characterization of cytochrome P450 4F subfamily: Functional role and response in inflammation

CYP4F subfamily comprises a group of enzymes that metabolize LTB4 to biologically less active metabolites. These inactive hydroxy products are incapable of chemotaxis and recruitment of inflammatory cells. This has led to a hypothesis that CYP4Fs may modulate inflammatory conditions serving as a signal of resolution. ^ We investigated the regulation of rat CYP4F gene expression under various inflammatory prompts including a bacterial lipopolysaccharide (LPS) treated model system, controlled traumatic brain injury (TBI) model as well as using direct cytokine challenges. CYP4Fs showed an isoform specific response to LPS. The pro-inflammatory cytokines IL-1β, IL-6 and TNF-α produced an overall inductive CYP4F response whereas IL-10, an anti-inflammatory cytokine, suppressed CYP4F gene expression in primary hepatocytes. The molecular mechanism behind IL-6 mediated CYP4F induction was partially STAT3 dependent. ^ An alternate avenue of triggering the inflammatory cascade is TBI, which is known to cause several secondary effects leading to multiorgan dysfunction syndrome. The results from this study elicited that trauma to the brain can produce acute inflammatory changes in organs distant from the injury site. Local production of LTB4 after CNS injury caused mobilization of inflammatory cells such as neutrophils to the lung. In the resolution phase, CYP4F expression increased with time along with the associated activity causing a decline in LTB4 concentration. This marked a significant reduction in neutrophil recruitment to the lung which led to subsequent recovery and repair. In addition, we showed that CYP4Fs are localized primarily in pulmonary endothelium. We speculate that the temporally regulated LTB4 clearance in the endothelium may be a novel target for treatment of pulmonary inflammation following injury. ^ In humans, several CYP4F isoforms have been identified and shown to metabolize LTB4 and other endogenous eicosanoids. However, the specific activity of the recently cloned human CYP4F11 is unknown. In the final part of this thesis, CYP4F11 protein was expressed in yeast in parallel to CYP4F3A. To our surprise, CYP4F11 displayed a different substrate profile than CYP4F3A. CYP4F3A metabolized eicosanoids while CYP4F11 was a better catalyst for therapeutic drugs. Thus, besides their endogenous function in clearing inflammation, CYP4Fs also may play a part in drug metabolism. ^

A systematic review of community-based participatory research interventions in pediatric and adolescent populations

Background. Community-based participatory research (CBPR) is a collaborative approach to research actively involving community members in all aspects of the research process. CBPR is not a new research method, but an approach that has gained increased attention in the field of public health over the last several years. Recognition of the inequalities in health status associated with social and environmental factors have led to calls for a renewed focus on ecological approaches to research. Ecological approaches acknowledge that the health of the community is dependent on an interaction between behavioral and environmental factors affecting the entire population. While many published studies document the benefits of CBPR in difficult-to-reach populations and describe successful implementation of this approach in adult populations, relatively few studies have been conducted in child and adolescent populations. Given that children and adolescents are particularly sensitive to the effects of their physical environments and may also be distrustful of outsiders, ecological approaches involving the community as partners, such as CBPR, may be especially useful in this population. ^ Objective. This thesis reviews published studies using a community-based participatory research approach in children and adolescents to assess the appropriateness of this approach in this population. ^ Method. Studies using CBPR in youth populations were identified using Medline and other Internet searches through both MeSH heading and text-word searches. ^ Results. A total of 16 studies were identified and analyzed for this review. Nine of the sixteen studies were experimental or quasi-experimental design, with Asthma being the most commonly studied disease. ^ Conclusions. While many studies using CBPR were not conducted with the level of scientific rigor typically found in clinical trial research, the studies reviewed each contributed to a greater understanding of the problems they investigated. Furthermore, interventional studies provided lasting benefits to communities under study above what would be found in studies using more traditional research approaches. While CBPR may not be appropriate for all research situations due to the time and resources required, we conclude that is a useful approach and should be considered when conducting community-based research for pediatric and adolescent populations.^

Relationship between dietary patterns and body mass index in Hispanic children ages 4--19 years of age

Background. In over 30 years, the prevalence of overweight for children and adolescents has increased across the United States (Barlow et al., 2007; Ogden, Flegal, Carroll, & Johnson, 2002). Childhood obesity is linked with adverse physiological and psychological issues in youth and affects ethnic/minority populations in disproportionate rates (Barlow et al., 2007; Butte et al., 2006; Butte, Cai, Cole, Wilson, Fisher, Zakeri, Ellis, & Comuzzie, 2007). More importantly, overweight in children and youth tends to track into adulthood (McNaughton, Ball, Mishra, & Crawford, 2008; Ogden et al., 2002). Childhood obesity affects body functions such as the cardiovascular, respiratory, gastrointestinal, and endocrine systems, including emotional health (Barlow et al., 2007, Ogden et al., 2002). Several dietary factors have been associated with the development of obesity in children; however, these factors have not been fully elucidated, especially in ethnic/minority children. In particular, few studies have been done to determine the effects of different meal patterns on the development of obesity in children. Purpose. The purpose of the study is to examine the relationships between daily proportions of energy consumed and energy derived from fat across breakfast, lunch, dinner, and snack, and obesity among Hispanic children and adolescents. Methods. A cross-sectional design was used to evaluate the relationship between dietary patterns and overweight status in Hispanic children and adolescents 4-19 years of age who participated in the Viva La Familia Study. The goal of the Viva La Familia Study was to evaluate genetic and environmental factors affecting childhood obesity and its co-morbidities in the Hispanic population (Butte et al., 2006, 2007). The study enrolled 1030 Hispanic children and adolescents from 319 families and examined factors related to increased body weight by focusing on a multilevel analysis of extensive sociodemographic, genetic, metabolic, and behavioral data. Baseline dietary intakes of the children were collected using 24-hour recalls, and body mass index was calculated from measured height and weight, and classified using the CDC standards. Dietary data were analyzed using a GEE population-averaged panel-data model with a cluster variable family identifier to include possible correlations within related data sets. A linear regression model was used to analyze associations of dietary patterns using possible covariates, and to examine the percentage of daily energy coming from breakfast, lunch, dinner, and snack while adjusting for age, sex, and BMI z-score. Random-effects logistic regression models were used to determine the relationship of the dietary variables with obesity status and to understand if the percent energy intake (%EI) derived from fat from all meals (breakfast, lunch, dinner, and snacks) affected obesity. Results. Older children (age 4-19 years) consumed a higher percent of energy at lunch and dinner and less percent energy from snacks compared to younger children. Age was significantly associated with percentage of total energy intake (%TEI) for lunch, as well as dinner, while no association was found by gender. Percent of energy consumed from dinner significantly differed by obesity status, with obese children consuming more energy at dinner (p = 0.03), but no associations were found between percent energy from fat and obesity across all meals. Conclusions. Information from this study can be used to develop interventions that target dietary intake patterns in obesity prevention programs for Hispanic children and adolescents. In particular, intervention programs for children should target dietary patterns with energy intake that is spread throughout the day and earlier in the day. These results indicate that a longitudinal study should be used to further explore the relationship of dietary patterns and BMI in this and other populations (Dubois et al., 2008; Rodriquez & Moreno, 2006; Thompson et al., 2005; Wilson et al., in review, 2008). ^

Effectiveness of dietary intervention in children and adolescents with elevated blood pressure

Hypertension is a known risk factor for cardiovascular disease in adults. Essential hypertension in children and adolescents is increasing in prevalence in the United States, and hypertension in children may track into adulthood. This increasing prevalence is attributed to the trends of increasing overweight and obese children and adolescents. Family history and being of African-American/black descent may predispose youth to elevated blood pressure. Interventions targeted to reduce and treat hypertension in youth include non-pharmaceutical interventions such as weight reduction, increased physical activity, and dietary changes and pharmaceutical treatment when indicated. The effectiveness of non-pharmaceutical interventions is well documented in adults, but there are limited studies with regards to children and adolescents, specifically in the arena of dietary interventions. Lifestyle modifications such as dietary interventions are the mainstay of recommended treatment for those children and adolescents with prehypertension or stage 1 hypertension. Given the association of being overweight and hypertension, efficacy of dietary interventions are of interest because of reduced cost, easy implementation and potential for multiple beneficial outcomes such as reduced weight and reduction of other metabolic or cardiovascular derangements. Barriers to dietary interventions often include socioeconomic status, ethnicity, personal, and external factors. The goal of this systematic review of the literature is to identify interventions targeted to children and adolescents that focus on recommended dietary changes related to blood pressure. Dietary interventions found for this review mostly focused on a particular nutrient or food group with the one notable exception that focused on the DASH pattern of eating. The effects of the interventions on blood pressure varied, but overall dietary modifications can be achieved in youth and can serve a role in producing positive outcomes on blood pressure. Increasing potassium and following a DASH diet seemed to provide the most clinically significant results. Further studies are still needed to evaluate long-term effectiveness and to contribute more supporting evidence for particular modifications in these age cohorts.^

"Gangsterism," HIV, and "tik:" An exploration of Cape Town youth

Since early 2000, the Western Cape of South Africa has been documented as an area for monitoring the spread of HIV. The majority of HIV cases occur within individuals between the ages of 15-49 years, and the epidemic is believed to be complicated by the increased use of crystal methamphetamine (CM), or “tik.” Eighty percent of current CM users in Cape Town are under the age of 21 years, and almost 18% of current HIV cases are in individuals under the age of 24 years. Gang membership in youth may also be complicating the HIV problem as gangs feed the social acceptability of “tik” and encourage sexual violence. With almost half the population of Cape Town in their mid-twenties, the threat of a new HIV epidemic complicated by CM use has become a concern in the young adults of the city. Research into the relationships between gang membership and drugs/violence has been extensively studied in the Cape Flats. Yet, few have examined the role of gangs in the perpetuation of HIV. Therefore, the purpose of this investigation was exploratory in nature. Key informant interviews from Cape Town youth were used as case illustrations to generate potential hypotheses on the interrelationships between “gangsterism,” “tik” use, and HIV. Such awareness is important if effective efforts to reduce HIV incidence in Cape Town (and Sub-Saharan Africa) are to transpire. If the problem of CM is not addressed quickly, the Cape Flats may find itself with a higher rate of an already uncontrollable HIV epidemic. ^

Evaluation of web-based resources for HIV+ youth

Given current rates of the Human Immunodeficiency Virus (HIV) in youth ages 15–24, comprehensive care is imperative in order to manage the virus and to prevent further transmission. In the past decade, the Internet has become an immensely popular source for information, including health information. Due to the increase in Internet use for this purpose, the assessment of the quality, accuracy, and timeliness of health information on the Internet is necessary since the information delivered may not be current or accurate. The purpose of this study was to determine the quantity and quality of websites containing health information and resources directed specifically towards HIV positive youth. Three general search terms, “HIV + teens”, “HIV teens info”, and “HIV infected teens,” were searched using the current top three search engines: Google, Yahoo!, and MSN/Bing. The first hundred hits of each search were then categorized by type of website. The examination of the search results yielded 7 sites that met the inclusion criteria. These sites were consequently evaluated on functionality and content using an adapted version of a pre-existing instrument. The functionality analysis revealed that no websites that contained self management information were dedicated specifically to HIV positive youth. The content analysis showed that the sites chosen for evaluation were mostly consistent with the guidelines provided by the Department of Health and Human Services. The most discussed topics in the sites included the importance of safer sexual behavior, HIV counseling, partner notification, safer behavior choices, such as condom use, and mental health. These results highlight the need for the development of accessible websites that contain accurate information targeting youth infected with HIV. This study provides a snapshot of the available web-based resources and health information for HIV positive youth, and is relevant for health educators, care providers, researchers, and others intervening with HIV+ youth. ^

Identification of genetic variants that influence atherosclerosis in young persons

Atherosclerosis is widely accepted as a complex genetic phenotype and is the usual cause of cardiovascular disease, the world’s leading killer. Genetic factors have been proven to be important risk contributors for atherosclerosis and much work has been done to identify promising candidates that might play a role in the development of atherosclerosis. It is well known that many independent replications are needed to unequivocally establish a valid genotype-phenotype association across different populations before the findings are extended to clinical settings and to the expensive follow-up studies designed to identify causal genetic variants. Aiming to replicate the association with atherosclerosis in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we assessed the relationship of 32 atherosclerosis candidate SNPs to atherosclerosis in the PDAY cohort, consisting of AA and EA young people aged 15-34 years who died of non-medical causes. Two association studies, a whole sample study and a 1:1 matched case control study were performed by use of multiple linear regression and logistic regression analyses, respectively. For the whole sample association study, 32 SNPs among 2,650 individuals (1,369 AA and 1,281 EA) were tested for the association with six early atherosclerosis phenotypes: abdominal aorta fatty streaks, abdominal aorta raised lesions, right coronary artery fatty streaks, right coronary artery raised lesions, thoracic aorta fatty streaks, and thoracic aorta raised lesions. For the matched case-control association study, 337 case-control paired samples were included; cases were chosen with the highest total raised lesion scores from the studied population, while controls were randomly selected from individuals that had no raised lesions and matched to cases by age, gender and race. Sixteen SNPs in 13 genes were found to be significantly associated with atherosclerosis in at least one of the PDAY association studies. Among these 16 findings: eight SNPs (rs9579646, rs6053733, rs3849150, rs10499903, rs2148079, rs5073691, rs10116277, and rs17228212) successfully replicated previous results, six SNPs (rs17222814, rs10811661, rs7028570, rs7291467, rs16996148 and rs10401969) were reported as new findings exclusive to our study, the last two of the 16 SNPs, rs501120 and rs6922269, showed either intriguing or conflicting result. SNP rs17222814 in ALOX5AP and SNP rs3849150 in LRRC18 were consistently associated with atherosclerosis in both prior and the two PDAY association studies. SNP rs3849150 was also identified to be highly correlated with a non-synonymous coding SNP, rs17772611, which may damage the protein (polyphen score = 0.996), suggesting that SNP rs17772611 may be the causal functional variant.^ In conclusion, our study added more support for the association of these candidate genes with atherosclerosis. SNPs rs3849150 and rs17772611 of LRRC18, as well as SNP rs17222814 of ALOX5AP, were the most significant findings from our study, and may be ranked among the best for further study.^

Molecular Mechanisms of Vascular Disease in Patients with Rare Variants in MYH11

Thoracic aortic aneurysms and dissections (TAAD) are the primary disease affecting the thoracic ascending aorta, with an incidence rate of 10.4/100,000. Although about 20% of patients carry a mutation in a single gene that causes their disease, the remaining 80% of patients may also have genetic factors that increase their risk for developing TAAD. Many of the genes that predispose to TAAD encode proteins involved in smooth muscle cell (SMC) contraction and the disease-causing mutations are predicted to disrupt contractile function. SMCs are the predominant cell type in the ascending aortic wall. Mutations in MYH11, encoding the smooth muscle specific myosin heavy chain, are a rare cause of inherited TAAD. However, rare but recurrent non-synonymous variants in MYH11 are present in the general population but do not cause inherited TAAD. The goal of this study was to assess the potential role of these rare variants in vascular diseases. Two distinct variants were selected: the most commonly seen rare variant, MYH11 R247C, and a duplication of the chromosomal region spanning the MYH11 locus at 16p13.1. Genetic analyses indicated that both of these variants were significantly enriched in patients with TAAD compared with controls. A knock-in mouse model of the Myh11 R247C rare variant was generated, and these mice survive and reproduce normally. They have no structural abnormalities of the aorta or signs of aortic disease, but do have decreased aortic contractility. Myh11R247C/R247C mice also have increased proliferative response to vascular injury in vivo and increased proliferation of SMCs in vitro. Myh11R247C/R247C SMCs have decreased contractile gene and protein expression and are dedifferentiated. In fibroblasts, myosin force generation is required for maturation of focal adhesions, and enhancers of RhoA activity replace enhancers of Rac1 activity as maturation occurs. Consistent with these previous findings, focal adhesions are smaller in Myh11R247C/R247C SMCs, and there is decreased RhoA activation. A RhoA activator (CN03) rescues the dedifferentiated phenotype of Myh11R247C/R247C SMCs. Myh11R247C/R247C mice were bred with an existing murine model of aneurysm formation, the Acta2-/- mouse. Over time, mice carrying the R247C allele in conjunction with heterozygous or homozygous loss of Acta2 had significantly increased aortic diameter, and a more rapid accumulation of pathologic markers. These results suggest that the Myh11 R247C rare variant acts as a modifier gene increasing the risk for and severity of TAAD in mice. In patients with 16p13.1 duplications, aortic MYH11 expression is increased, but there is no corresponding increase in smooth muscle myosin heavy chain protein. Using SMCs that overexpress Myh11, we identified alterations in SMC phenotype leading to excessive protein turnover. All contractile proteins, not just myosin, are affected, and the proteins are turned over by autophagic degradation. Surprisingly, these cells are also more contractile compared with wild-type SMCs. The results described in this dissertation firmly establish that rare variants in MYH11 significantly affect the phenotype of SMCs. Further, the data suggests that these rare variants do increase the risk of TAAD via pathways involving altered SMC phenotype and contraction. Therefore, this study validates that these rare genetic variants alter vascular SMCs and provides model systems to explore the contribution of rare variants to disease.

The impact of school year work on adolescent *development

In recent decades, work has become an increasingly common feature of adolescent life in the United States. Once assumed to be an inherently positive experience for youth, school year work has recently been associated with several adverse effects, especially as the number of hours of weekly work increases. The purpose of this dissertation was to describe the impact of school year work on adolescent development in a sample of high school students from rural South Texas, an area where economically-disadvantaged and Hispanic students are heavily represented.^ The first study described the prevalence and work circumstances of 3,565 10$\rm\sp{th}$ and 12$\rm\sp{th}$ grade students who responded to anonymous surveys conducted in regular classrooms. The overall prevalence of current work was 53%. Prevalence differed by grade, college-noncollege-bound status, and parent education. Fifty percent of employed students worked to support consumer spending.^ The second study examined the effects of four levels of work intensity on the academic, behavioral, social, mental and physical health of students. The following negative effects of intense work were reported: (1) decreased engagement in school, satisfaction with leisure time, and hours of weeknight and weekend sleep, and (2) increased health risk behaviors and psychological stress. The negative effects of intense work differed by gender, grade, ethnicity, but not by parent education.^ The third study described the prevalence of injury in the study population. A dose response effect was observed where increasing hours of weekly work were significantly related to work-related injury. The likelihood of being injured while employed in restaurant, farm/ranch, and construction work was greater than the probability of being injured while working in factory/office/skilled, yard, or retail work when compared to babysitting. Cuts, shocks/burns and sprains were the most common injuries in working teens.^ Students, parents, educators, health professionals and policymakers should continue to monitor the number of weekly hours that students work during the school year. ^

Urban trees and atmospheric pollutants in big cities: Effects in Madrid

Una investigación sobre la mejora de la contaminación del aire (CA) por medio de arbolado urbano se realizó en Madrid, una ciudad con casi 4 M de habitantes, 2,8 M de vehículos y casi 3 M de árboles de mantenimiento público. La mayoría de los árboles estaban en dos bosques periurbanos. Los 650.000 restantes era pies de alineación y parques. Los taxones estudiados fueron Platanus orientalis (97.205 árboles), Ulmus sp. (70.557), Pinus pinea (49.038), Aesculus hippocastanum (22.266), Cedrus sp. (13.678) y Quercus ilex (1.650), de calles y parques. Muestras foliares se analizaron en diferentes épocas del año, así como datos de contaminación por PM10 de 28 estaciones de medición de la contaminación durante 30 años, y también la intensidad del tráfico (IMD) en 2.660 calles. La acumulación de metales pesados (MP) sobre hojas y dentro de estas se estimó en relación con la CA y del suelo y la IMD del tráfico. La concentración media de Ba, Cd, Cr, Cu, Mn, Ni, Pb y Zn en suelo (materia seca) alcanzó: 489,5, 0,7, 49,4, 60,9, 460,9, 12,8, 155,9 y 190,3 mg kg-1 respectivamente. Los árboles urbanos, particularmente coníferas (debido a la mayor CA en invierno) contribuyen significativamente a mejorar la CA sobre todo en calles con alta IMD. La capacidad de las seis sp. para capturar partículas de polvo en su superficies foliares está relacionada con la IMD del tráfico y se estimó en 16,8 kg/año de MP tóxicos. Pb y Zn resultaron ser buenos marcadores antrópicos en la ciudad en relación con el tráfico, que fue la principal fuente de contaminación en los árboles y suelos de Madrid. Las especies de árboles variaron en función de su capacidad para capturar partículas (dependiendo de las propiedades de sus superficies foliares) y acumular los MP absorbidos de los suelos. Las concentraciones foliares de Pb y Zn estuvieron por encima de los límites establecidos en diferentes sitios de la ciudad. La microlocalización de Zn mediante microscópico mostró la translocación al xilema y floema. Se detectaron puntos de contaminación puntual de Cu and Cr en antiguos polígonos industriales y la distribución espacial de los MP en los suelos de Madrid mostró que en incluso en zonas interiores del El Retiro había ciertos niveles elevados de [Pb] en suelo, tal vez por el emplazamiento la Real Fábrica de Porcelana en la misma zona hace 200 años. Distintas áreas del centro de la ciudad también alcanzaron niveles altos de [Pb] en suelo. Según los resultados, el empleo de una combinación de Pinus pinea con un estrato intermedio de Ulmus sp. y Cedrus sp. puede ser la mejor recomendación como filtro verde eficiente. El efecto del ozono (O3) sobre el arbolado en Madrid fue también objeto de este estudio. A pesar de la reducción de precursores aplicada en muchos países industrializados, O3 sigue siendo la principal causa de CA en el hemisferio norte, con el aumento de [O3] de fondo. Las mayores [O3] se alcanzaron en regiones mediterráneas, donde el efecto sobre la vegetación natural es compensado por el xeromorfismo y la baja conductancia estomática en respuesta los episodios de sequía estival característicos de este clima. Durante una campaña de monitoreo, se identificaron daños abióticos en hojas de encina parecidos a los de O3 que estaban plantadas en una franja de césped con riego del centro de Madrid. Dada la poca evidencia disponible de los síntomas de O3 en frondosas perennifolias, se hizo un estudio que trató de 1) confirman el diagnóstico de daño de O3, 2) investigar el grado de los síntomas en encinas y 3) analizar los factores ambientales que contribuyeron a los daños por O3, en particular en lo relacionado con el riego. Se analizaron los marcadores macro y micromorfológicos de estrés por O3, utilizando las mencionadas encinas a modo de parcela experimental. Los síntomas consistieron en punteado intercostal del haz, que aumentó con la edad. Además de un punteado subyacente, donde las células superiores del mesófilo mostraron reacciones características de daños por O3. Las células próximas a las zonas dañadas, presentaron marcadores adicionales de estrés oxidativo. Estos marcadores morfológicos y micromorfológicos de estrés por O3 fueron similares a otras frondosas caducifolias con daños por O3. Sin embargo, en nuestro caso el punteado fue evidente con AOT40 de 21 ppm•h, asociada a riego. Análisis posteriores mostraron que los árboles con riego aumentaron su conductancia estomática, con aumento de senescencia, manteniéndose sin cambios sus características xeromórficas foliares. Estos hallazgos ponen de relieve el papel primordial de la disponibilidad de agua frente a las características xeromórficas a la hora de manifestarse los síntomas en las células por daños de O3 en encina. ABSTRACT Research about air pollution mitigation by urban trees was conducted in Madrid (Spain), a southern European city with almost 4 M inhabitants, 2.8 M daily vehicles and 3 M trees under public maintenance. Most trees were located in two urban forests, while 650'000 trees along urban streets and in parks. The urban taxa included Platanus orientalis (97'205 trees), Ulmus sp. (70’557), Pinus pinea (49'038), Aesculus hippocastanum (22’266), Cedrus sp. (13'678 and Quercus ilex (1'650) along streets and parks. Leave samples were analysed sequentially in different seasons, PM10 data from 28 air monitoring stations during 30 years and traffic density estimated from 2’660 streets. Heavy metal (HM) accumulation on the leaf surface and within leaves was estimated per tree related to air and soil pollution, and traffic intensity. Mean concentration of Ba, Cd, Cr, Cu, Mn, Ni, Pb and Zn in topsoil samples (dry mass) amounted in Madrid: 489.5, 0.7, 49.4, 60.9, 460.9, 12.8, 155.9 and 190.3 mg kg-1 respectively. Urban trees, particularly conifers (due to higher pollution in winter) contributed significantly to alleviate air pollution especially near to high ADT roads. The capacity of the six urban street trees species to capture air-born dust on the foliage surface as related to traffic intensity was estimated to 16.8 kg of noxious metals from exhausts per year. Pb and Zn pointed to be tracers of anthropic activity in the city with vehicle traffic as the main source of diffuse pollution on trees and soils. Tree species differed by their capacity to capture air-borne dust (by different leaf surface properties) and to allocate HM from soils. Pb and Zn concentrations in the foliage were above limits in different urban sites and microscopic Zn revelation showed translocation in xylem and phloem tissue. Punctual contamination in soils by Cu and Cr was identified in former industrial areas and spatial trace element mapping showed for central Retiro Park certain high values of [Pb] in soils even related to a Royal pottery 200 years ago. Different areas in the city centre also reached high levels [Pb] in soils. According to the results, a combination of Pinus pinea with understorey Ulmus sp. and Cedrus sp. layers can be recommended for the best air filter efficiency. The effects of ozone (O3) on trees in different areas of Madrid were also part of this study. Despite abatement programs of precursors implemented in many industrialized countries, ozone remained the main air pollutant throughout the northern hemisphere with background [O3] increasing. Some of the highest ozone concentrations were measured in regions with a Mediterranean climate but the effect on the natural vegetation is alleviated by low stomatal uptake and frequent leaf xeromorphy in response to summer drought episodes characteristic of this climate. During a bioindication survey, abiotic O3-like injury was identified in foliage. Trees were growing on an irrigated lawn strip in the centre of Madrid. Given the little structural evidence available for O3 symptoms in broadleaved evergreen species, a study was undertaken in 2007 with the following objectives 1) confirm the diagnosis, 2) investigate the extent of symptoms in holm oaks growing in Madrid and 3) analyse the environmental factors contributing to O3 injury, particularly, the site water supply. Therefore, macro- and micromorphological markers of O3 stress were analysed, using the aforementioned lawn strip as an intensive study site. Symptoms consisted of adaxial and intercostal stippling increasing with leaf age. Underlying stippling, cells in the upper mesophyll showed HR-like reactions typical of ozone stress. The surrounding cells showed further oxidative stress markers. These morphological and micromorphological markers of ozone stress were similar to those recorded in deciduous broadleaved species. However, stippling became obvious already at an AOT40 of 21 ppm•h and was primarily found at irrigated sites. Subsequent analyses showed that irrigated trees had their stomatal conductance increased and leaf life-span reduced whereas their leaf xeromorphy remained unchanged. These findings suggest a central role of water availability versus leaf xeromorphy for ozone symptom expression by cell injury in holm oak.

Modeling and Simulation of Upper Brachial Plexus Injury

This article presents the first musculoskeletal model and simulation of upper plexus brachial injury. From this model is possible to analyse forces and movement ranges in order to develop a robotic exoskeleton to improve rehabilitation. The software that currently exists for musculoskeletal modeling is varied and most have advanced features for proper analysis and study of motion simulations. Whilst more powerful computer packages are usually expensive, there are other free and open source packages available which offer different tools to perform animations and simulations and which obtain forces and moments of inertia. Among them, Musculoskeletal Modeling Software was selected to construct a model of the upper limb, which has 7 degrees of freedom and 10 muscles. These muscles are important for two of the movements simulated in this article that are part of the post-surgery rehabilitation protocol. We performed different movement animations which are made using the inertial measurement unit to capture real data from movements made by a human being. We also performed the simulation of forces produced in elbow flexion-extension and arm abduction-adduction of a healthy subject and one with upper brachial plexus injury in a postoperative state to compare the force that is capable of being produced in both cases.

Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the Src-family kinases Hck and Fgr

Signal transduction through the leukocyte integrins is required for the processes of firm adhesion, activation, and chemotaxis of neutrophils during inflammatory reactions. Neutrophils isolated from knockout mice that are deficient in the expression of p59/61hck (Hck) and p58c-fgr (Fgr), members of the Src-family of protein tyrosine kinases, have been shown to be defective in adhesion mediated activation. Cells from these animals have impaired induction of respiratory burst and granule secretion following plating on surfaces that crosslink β2 and β3 integrins. To determine if the defective function of hck−/−fgr−/− neutrophils observed in vitro also results in impaired inflammatory responses in vivo, we examined responses induced by lipopolysaccharide (LPS) injection in these animals. The hck−/−fgr−/− mice showed marked resistance to the lethal effects of high-dose LPS injection despite the fact that high levels of serum tumor necrosis factor α and interleukin 1α were detected. Serum chemistry analysis revealed a marked reduction in liver and renal damage in mutant mice treated with LPS, whereas blood counts showed a marked neutrophilia that was not seen in wild-type animals. Direct examination of liver sections from mutant mice revealed reduced neutrophil migration into the tissue. These data demonstrate that defective integrin signaling in neutrophils, caused by loss of Hck and Fgr tyrosine kinase activity, results in impaired inflammation-dependent tissue injury in vivo.

In vivo inhibition of rat stellate cell activation by soluble transforming growth factor β type II receptor: A potential new therapy for hepatic fibrosis

Transforming growth factor β (TGF-β) is a well characterized cytokine that appears to play a major role in directing the cellular response to injury, driving fibrogenesis, and, thus, potentially underlying the progression of chronic injury to fibrosis. In this study, we report the use of a novel TGF-β receptor antagonist to block fibrogenesis induced by ligation of the common bile duct in rats. The antagonist consisted of a chimeric IgG containing the extracellular portion of the TGF-β type II receptor. This “soluble receptor” was infused at the time of injury; in some experiments it was given at 4 days after injury, as a test of its ability to reverse fibrogenesis. The latter was assessed by expression of collagen, both as the mRNA in stellate cells isolated from control or injured liver and also by quantitative histochemistry of tissue sections. When the soluble receptor was administered at the time of injury, collagen I mRNA in stellate cells from the injured liver was 26% of that from animals receiving control IgG (P < 0.0002); when soluble receptor was given after injury induction, collagen I expression was 35% of that in control stellate cells (P < 0.0001). By quantitative histochemistry, hepatic fibrosis in treated animals was 55% of that in controls. We conclude that soluble TGF-β receptor is an effective inhibitor of experimental fibrogenesis in vivo and merits clinical evaluation as a novel agent for controlling hepatic fibrosis in chronic liver injury.

Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses

Hepatic fibrosis represents the generalized response of the liver to injury and is characterized by excessive deposition of extracellular matrix. The cellular basis of this process is complex and involves interplay of many factors, of which cytokines are prominent. We have identified divergent fibrosing responses to injury among mouse strains and taken advantage of these differences to examine and contrast T helper (Th)-derived cytokines during fibrogenesis. Liver injury was induced with carbon tetrachloride, fibrosis was quantitated, and Th1/Th2 cytokine mRNAs measured. Liver injury in BALB/c mice resulted in severe fibrosis, whereas C57BL/6 mice developed comparatively minimal fibrosis. Fibrogenesis was significantly modified in T and B cell-deficient BALB/c and C57BL/6 severe combined immunodeficient (SCID) mice compared with wild-type counterparts, suggesting a role of Th subsets. Fibrogenic BALB/c mice exhibited a Th2 response during the wounding response, whereas C57BL/6 mice displayed a Th1 response, suggesting that hepatic fibrosis is influenced by different T helper subsets. Moreover, mice lacking interferon γ, which default to the Th2 cytokine pathway, exhibited more pronounced fibrotic lesions than did wild-type animals. Finally, shifting of the Th2 response toward a Th1 response by treatment with neutralizing anti-interleukin 4 or with interferon γ itself ameliorated fibrosis in BALB/c mice. These data support a role for immune modulation of hepatic fibrosis and suggest that Th cytokine subsets can modulate the fibrotic response to injury.