Association between thyroid dysfunction and venous thromboembolism in the elderly: a prospective cohort study.

BACKGROUND Venous thromboembolism (VTE) and subclinical thyroid dysfunction (SCTD) are both common in elderly patients. SCTD has been related to a hypercoagulable state and increased thromboembolic risk. However, prospective data on the relationship between SCTD and VTE are lacking. OBJECTIVES To investigate the relationship between SCTD and recurrent VTE (rVTE), all-cause mortality, and thrombophilic biomarkers. PATIENTS Elderly participants with VTE. METHODS In a prospective multicenter cohort, thyroid hormones and thrombophilic biomarkers were measured 1 year after acute VTE, as both may be influenced by acute thrombosis. We defined subclinical hypothyroidism (SHypo) as elevated thyroid stimulating hormone levels (TSH=4.50-19.99 mIU/l), and subclinical hyperthyroidism (SHyper) as TSH<0.45, both with normal free thyroxine levels. Outcomes were incidence of rVTE and overall mortality during follow-up starting after the 1-year blood sampling. RESULTS Of 561 participants (58% with anticoagulation), 6% had SHypo and 5% SHyper. After 20.8 months of mean follow-up, 9% developed rVTE and 10% died. rVTE incidence rate was 7.2 (95% confidence interval:2.7-19.2) per 100 patient-years in SHypo, 0.0 (0.0-7.6) in SHyper and 5.9 (4.4-7.8) in euthyroid participants. In multivariate analyses, the sub-hazard ratio [SHR] for rVTE was 0.00 (0.00-0.58) in SHyper and 1.50 (0.52-4.34) in SHypo compared to euthyroids, without increased thrombophilic biomarkers. SHyper (HR 0.80,0.23-2.81) and SHypo (HR 0.99,0.30-3.29) were not associated with mortality. CONCLUSION In elderly patients, SHyper may be associated with lower rVTE risks. SHypo showed a non-statistically significant pattern of an association with rVTE, without increased mortality or differences in thrombophilic biomarkers. This article is protected by copyright. All rights reserved.

Serum amyloid A: high-density lipoproteins interaction and cardiovascular risk.

AIMS High-density lipoproteins (HDLs) are considered as anti-atherogenic. Recent experimental findings suggest that their biological properties can be modified in certain clinical conditions by accumulation of serum amyloid A (SAA). The effect of SAA on the association between HDL-cholesterol (HDL-C) and cardiovascular outcome remains unknown. METHODS AND RESULTS We examined the association of SAA and HDL-C with mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, which included 3310 patients undergoing coronary angiography. To validate our findings, we analysed 1255 participants of the German Diabetes and Dialysis study (4D) and 4027 participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study. In LURIC, SAA concentrations predicted all-cause and cardiovascular mortality. In patients with low SAA, higher HDL-C was associated with lower all-cause and cardiovascular mortality. In contrast, in patients with high SAA, higher HDL-C was associated with increased all-cause and cardiovascular mortality, indicating that SAA indeed modifies the beneficial properties of HDL. We complemented these clinical observations by in vitro experiments, in which SAA impaired vascular functions of HDL. We further derived a formula for the simple calculation of the amount of biologically 'effective' HDL-C based on measured HDL-C and SAA from the LURIC study. In 4D and KORA S4 studies, we found that measured HDL-C was not associated with clinical outcomes, whereas calculated 'effective' HDL-C significantly predicted better outcome. CONCLUSION The acute-phase protein SAA modifies the biological effects of HDL-C in several clinical conditions. The concomitant measurement of SAA is a simple, useful, and clinically applicable surrogate for the vascular functionality of HDL.

Dysphagia in Acute Stroke: Incidence, Burden and Impact on Clinical Outcome.

BACKGROUND Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke. METHODS We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia. RESULTS Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality. CONCLUSION Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization.

Nonlinear tests for genetic studies of complex disease

Linkage and association studies are major analytical tools to search for susceptibility genes for complex diseases. With the availability of large collection of single nucleotide polymorphisms (SNPs) and the rapid progresses for high throughput genotyping technologies, together with the ambitious goals of the International HapMap Project, genetic markers covering the whole genome will be available for genome-wide linkage and association studies. In order not to inflate the type I error rate in performing genome-wide linkage and association studies, multiple adjustment for the significant level for each independent linkage and/or association test is required, and this has led to the suggestion of genome-wide significant cut-off as low as 5 × 10 −7. Almost no linkage and/or association study can meet such a stringent threshold by the standard statistical methods. Developing new statistics with high power is urgently needed to tackle this problem. This dissertation proposes and explores a class of novel test statistics that can be used in both population-based and family-based genetic data by employing a completely new strategy, which uses nonlinear transformation of the sample means to construct test statistics for linkage and association studies. Extensive simulation studies are used to illustrate the properties of the nonlinear test statistics. Power calculations are performed using both analytical and empirical methods. Finally, real data sets are analyzed with the nonlinear test statistics. Results show that the nonlinear test statistics have correct type I error rates, and most of the studied nonlinear test statistics have higher power than the standard chi-square test. This dissertation introduces a new idea to design novel test statistics with high power and might open new ways to mapping susceptibility genes for complex diseases. ^

Defining barriers in caring for seriously-ill children in a resource-limited setting: An observational study of 2 children's hospitals in Haiti

Background. According to the WHO 2007 country report, Haiti lags behind the Millennium Development Goal of reducing child mortality and maintains the highest under-5 mortality rate in the Western hemisphere. 3 Overall, few studies exist that seek to better grasp barriers in caring for a seriously ill child in a resource-limited setting and only a handful propose sustainable, effective interventions. ^ Objectives. The objectives of this study are to describe the prevalence of serious illnesses among children hospitalized at 2 children's hospitals in Port au Prince, to determine the barriers faced when caring for seriously ill children, and to report hospital outcomes of children admitted with serious illnesses. ^ Methods. Data were gathered from 2 major children's hospitals in Port au Prince, Haiti (Grace Children's Hospital [GCH] and Hopital d l'Universite d'Etat d'Haiti [HUEH]) using a triangulated approach of focus group discussions, physician questionnaires, and retrospective chart review. 23 pediatric physicians participated in focus group discussions and completed a self-administered questionnaire evaluating healthcare provider knowledge, self-efficacy, and perceived barriers relating to the care of seriously ill children in a resource-limited setting. A sample of 240 patient charts meeting eligibility criteria was abstracted for pertinent elements including sociodemographics, documentation, treatment strategies, and outcomes. Factors associated with mortality were analyzed using χ2 test and Fisher exact test [Minitab v.15]. ^ Results. The most common primary diagnoses at admission were gastroenteritis with moderate dehydration (35.5%), severe malnutrition (25.8%), and pneumonia (19.3%) for GCH, and severe malnutrition (32.6%), sepsis (24.7%), and severe respiratory distress (18%) for HUEH. Overall, 12.9% and 27% of seriously ill patients presented with shock to GCH and HUEH, respectively. ^ Shortage of necessary materials and equipment represented the most commonly reported limitation (18/23 respondents). According to chart data, 9.4% of children presenting with shock did not receive a fluid bolus, and only 8% of patients presenting with altered mental status or seizures received a glucose check. 65% of patients with meningitis did not receive a lumbar puncture due to lack of materials. ^ Hospital mortality rates did not differ by gender or by institution. Children who died were more likely to have a history of prematurity (OR 4.97 [95% CI 1.32-18.80]), an incomplete vaccination record (OR 4.05 [95% CI 1.68-9.74]), or a weight for age ≤3rd percentile (OR 6.1 [95% CI 2.49-14.93]. Case-fatality rates were significantly higher among those who presented with signs of shock compared with those who did not (23.1% vs. 10.7%, RR=2.16, p=0.03). Caregivers did not achieve shock reversal in 21% of patients and did not document shock reversal in 50% of patients. ^ Conclusions. Many challenges face those who seek to optimize care for seriously ill children in resource-limited settings. Specifically, in Haiti, qualitative and quantitative data suggest major issues with lack of supplies, pre-hospital factors, including malnutrition as a comorbidity, and early recognition and management of shock. A tailored intervention designed to address these issues is needed in order to prospectively evaluate improvements in child mortality in a high-risk population.^

Near infra-red-activatable nanocarriers for selective cancer diagnosis and treatment

Standard treatment strategies for cancer patients include surgery, radiation therapy, and chemotherapy. Although these strategies have been proven effective, they also have associated limitations. An attractive and innovative approach that can be used alone or in combination with the above modalities is based on the systemic or topical administration of a nanomaterial-based photoactive compound. Interaction with light in the near infrared (NIR) region results in either emission of fluorescence, which can be used for photodetection, or absorption of light which results in phototherapy. Nanomaterials have the advantage of providing multi-functional and unique properties in a single device that cannot be readily acquired with conventional small molecular weight compounds. ^ In this study, three different novel nanocarrier systems were designed and evaluated in mediating photodetection and phototherapy in the NIR. The first compound synthesized was a dual-labeled magnetic resonance/optical imaging agent for sentinel lymph node mapping and biopsy. This dual-labeled agent combines the high resolution of magnetic resonance imaging with the highly sensitive detection of optical imaging. The second imaging agent was an activatable optical imaging agent used to monitor cathepsin B activity in vivo and to probe the degradation of poly(L-glutamic acid). This polymeric nanocarrier offers highly sensitive technique for the detection of enzymatic activity, with is not yet possible with small molecular weight compounds. The third agent was a C225-conjugated hollow nanoshell that is targeted to epidermal growth factor receptors. This targeting agent has been demonstrated to mediate photothermal therapy both in vitro and in vivo. ^ These nanocarrier systems are an invaluable tool for the detection of cancer and many other diseases. With improved targeted delivery of these agents, the ability to diagnose diseases will become more sensitive and more specific. Finally, when designed properly, these agents would allow concurrent diagnosis and treatment of patients of various diseases. ^

AN ASSESSMENT OF AFLATOXIN B1, AND OTHER SELECTED VARIABLES, IN A RURAL ENVIRONMENT AND ASSOCIATED CANCER RISK (TEXAS)

A study to assess possible exposure to carcinogenic metabolites (aflatoxins) from a mold Aspergillus flavus has been made in a rice producing area of Brazoria County, Texas. One hundred samples of unmilled rice were analyzed by thin-layer chromatography (TLC) for the amount of aflatoxin produced by the mold during rice growth and storage. Two well water samples and two rice elevator dust samples were also checked for possible aflatoxin content. The mortality rates from gastrointestinal and urinary tract cancers in the rice-growing part of the county were compared with mortality rates in the nonrice-producing areas of the same county.^ This study was an outgrowth of an earlier investigation by Cech and co-workers in Brazoria County which focused on environmental differences, specifically on the quality of drinking water in the former residences of decedents from primary liver cancer. It also compared subjects who died from other causes. The author of this dissertation participated in this phase of the overall investigation by performing some of the chemical analyses and by preparing synographic maps of water quality, and thus, part of those results from the early phase is also included in this manuscript.^ No aflatoxin was detected by TLC methods. However, when extracts of rice dust were checked for mutagenesis by the Ames Salmonella-microsome assay as a supplement to the TLC analysis, the result suggested that these dusts might have contained mutagenic material. The age-adjusted mortality rates in the rice-growing area were higher than those in the comparison area for both male and female gastrointestinal tract cancer and for male urinary tract cancer, but the differences were not statistically significant. ^

Elevated cystatin C & heart failure prognosis a systematic review

Renal insufficiency is one of the most common co-morbidities present in heart failure (HF) patients. It has significant impact on mortality and adverse outcomes. Cystatin C has been shown as a promising marker of renal function. A systematic review of all the published studies evaluating the prognostic role of cystatin C in both acute and chronic HF was undertaken. A comprehensive literature search was conducted involving various terms of 'cystatin C' and 'heart failure' in Pubmed medline and Embase libraries using Scopus database. A total of twelve observational studies were selected in this review for detailed assessment. Six studies were performed in acute HF patients and six were performed in chronic HF patients. Cystatin C was used as a continuous variable, as quartiles/tertiles or as a categorical variable in these studies. Different mortality endpoints were reported in these studies. All twelve studies demonstrated a significant association of cystatin C with mortality. This association was found to be independent of other baseline risk factors that are known to impact HF outcomes. In both acute and chronic HF, cystatin C was not only a strong predictor of outcomes but also a better prognostic marker than creatinine and estimated glomerular filtration rate (eGFR). A combination of cystatin C with other biomarkers such as N terminal pro B- type natriuretic peptide (NT-proBNP) or creatinine also improved the risk stratification. The plausible mechanisms are renal dysfunction, inflammation or a direct effect of cystatin C on ventricular remodeling. Either alone or in combination, cystatin C is a better, accurate and a reliable biomarker for HF prognosis. ^

Evaluación de aceites y extractos vegetales para el control de Sitophilus zeamaiz y su efecto en la calidad de semilla de maíz

Sitophilus zeamaiz es una de las especies de gorgojos que más pérdidas causa en granos almacenados en el mundo; su control se basa principalmente en productos sintéticos, que con el paso del tiempo resultan menos efectivos. En la presente investigación se evaluaron aceites vegetales de ricino, soya y extractos vegetales de neem y lila sobre poblaciones de S. zeamaiz y sus efectos sobre la germinación y parámetros fisiológicos de las plántulas. Los resultados muestran que el aceite de soya dio los mejores resultados de control, al presentar mortalidades entre un 92 y 100% a las 192 horas. Sin embargo, este aceite afecta la germinación a dosis de 2000 a 10000 ppm. El extracto de neem presentó mortalidades del 78,75 y 91,25% a las 192 horas, sin afectar la germinación ni las propiedades agronómicas. Finalmente, el aceite de ricino y el extracto de lila fueron los tratamientos que, para las condiciones del presente estudio, no mostraron altas mortalidades sobre S. zeamaiz.

Toxina botulínica para la secreción descontrolada de saliva : presentación de un caso

La neurotoxina botulínica es producida por la bacteria anaerobia Clostridium botulinum (NTBo). Bloquea la transmisión neuromuscular por lo cual es utilizada para el tratamiento de enfermedades con hiperactividad muscular, bloqueando la liberación de acetilcolina y así la transmisión sináptica en la unión neuromuscular, lo que lleva al debilitamiento y atrofia de los músculos. Este mecanismo de acción motivó el uso de la toxina botulínica en las enfermedades con elevado tono muscular, como la distonía y la espasticidad, por lo cual también ha revolucionado la opción de tratamiento de los trastornos autónomos de hipersecreción. La sialorrea es un síntoma común en diversas enfermedades neurológicas. Las inyecciones de toxina botulínica, guiadas por ultrasonidos en las glándulas salivales, produce una disminución de la salivación excesiva en niños con deficiencias neurológicas como parálisis cerebral. La utilización de la toxina botulínica tipo A ha sido sugerida como tratamiento de la sialorrea en pacientes con parálisis cerebral (PC). Esta recomendación ha sido hecha por el efecto anticolinérgico de esta sustancia, principalmente por su capacidad para bloquear la liberación de acetilcolina a nivel de las membranas pre-sinápticas Aunque la respuesta al tratamrento es distinta en cada niño, en general se ha observado que cuanto más a menudo se utiliza la toxlna botulínica y más alta es la dosis utilizada, los resultados son mejores. Los expertos consideran conveniente el procedimiento porque muchos de estos pacientes están utilizando la toxina botulínica para sus problemas musculares y las distrntas condiciones pueden ser tratadas al mismo tiempo Se reporta la descripción de la aplicación de toxina botulínica en una paciente niña que concurre al Instituto de Rehabilitación Infantil TELETON de la ciudad de Valparaíso, Chile, con un trastorno motor severo y con salivación incontrolada persistente que provoca enfermedades respiratorias a repetición

Compromisos en la adaptación a distintos huéspedes en virus de plantas

Los patógenos han desarrollado estrategias para sobrevivir en su entorno, infectar a sus huéspedes, multiplicarse dentro de estos y posteriormente transmitirse a otros huéspedes. Todos estos componentes hacen parte de la eficacia biológica de los patógenos, y les permiten ser los causantes de enfermedades infecciosas tanto en hombres y animales, como en plantas. El proceso de infección produce efectos negativos en la eficacia biológica del huésped y la gravedad de los efectos, dependerá de la virulencia del patógeno. Por su parte, el huésped ha desarrollado mecanismos de respuesta en contra del patógeno, tales como la resistencia, por la que reduce la multiplicación del patógeno, o la tolerancia, por la que disminuye el efecto negativo de la infección. Estas respuestas del huésped a la infección producen efectos negativos en la eficacia biológica del patógeno, actuando como una presión selectiva sobre su población. Si la presión selectiva sobre el patógeno varía según el huésped, se predice que un mismo patógeno no podrá aumentar su eficacia biológica en distintos huéspedes y estará más adaptado a un huésped y menos a otro, disminuyendo su gama de huéspedes. Esto supone que la adaptación de un patógeno a distintos huéspedes estará a menudo dificultada por compromisos (trade-off) en diferentes componentes de la eficacia biológica del patógeno. Hasta el momento, la evidencia de compromisos de la adaptación del patógeno a distintos huéspedes no es muy abundante, en lo que se respecta a los virus de plantas. En las últimas décadas, se ha descrito un aumento en la incidencia de virus nuevos o previamente descritos que producen enfermedades infecciosas con mayor gravedad y/o diferente patogenicidad, como la infección de huéspedes previamente resistentes. Esto se conoce como la emergencia de enfermedades infecciosas y está causada por patógenos emergentes, que proceden de un huésped reservorio donde se encuentran adaptados. Los huéspedes que actúan como reservorios pueden ser plantas silvestres, que a menudo presentan pocos síntomas o muy leves a pesar de estar infectados con diferentes virus, y asimismo se encuentran en ecosistemas con ninguna o poca intervención humana. El estudio de los factores ecológicos y biológicos que actúan en el proceso de la emergencia de enfermedades infecciosas, ayudará a entender sus causas para crear estrategias de prevención y control. Los virus son los principales patógenos causales de la emergencia de enfermedades infecciosas en humanos, animales y plantas y un buen modelo para entender los procesos de la emergencia. Asimismo, las plantas a diferencia de los animales, son huéspedes fáciles de manipular y los virus que las afectan, más seguros para el trabajo en laboratorio que los virus de humanos y animales, otros modelos también usados en la investigación. Por lo tanto, la interacción virus – planta es un buen modelo experimental para el estudio de la emergencia de enfermedades infecciosas. El estudio de la emergencia de virus en plantas tiene también un interés particular, debido a que los virus pueden ocasionar pérdidas económicas en los cultivos agrícolas y poner en riesgo la durabilidad de la resistencia de plantas mejoradas, lo que supone un riesgo en la seguridad alimentaria con impactos importantes en la sociedad, comparables con las enfermedades infecciosas de humanos y animales domésticos. Para que un virus se convierta en un patógeno emergente debe primero saltar desde su huésped reservorio a un nuevo huésped, segundo adaptarse al nuevo huésped hasta que la infección dentro de la población de éste se vuelva independiente del reservorio y finalmente debe cambiar su epidemiología. En este estudio, se escogió la emergencia del virus del mosaico del pepino dulce (PepMV) en el tomate, como modelo experimental para estudiar la emergencia de un virus en una nueva especie de huésped, así como las infecciones de distintos genotipos del virus del moteado atenuado del pimiento (PMMoV) en pimiento, para estudiar la emergencia de un virus que aumenta su patogenicidad en un huésped previamente resistente. El estudio de ambos patosistemas nos permitió ampliar el conocimiento sobre los factores ecológicos y evolutivos en las dos primeras fases de la emergencia de enfermedades virales en plantas. El PepMV es un patógeno emergente en cultivos de tomate (Solanum lycopersicum) a nivel mundial, que se describió primero en 1980 infectando pepino dulce (Solanum muricatum L.) en Perú, y casi una década después causando una epidemia en cultivos de tomate en Holanda. La introducción a Europa posiblemente fue a través de semillas infectadas de tomate procedentes de Perú, y desde entonces se han descrito nuevos aislados que se agrupan en cuatro cepas (EU, LP, CH2, US1) que infectan a tomate. Sin embargo, el proceso de su emergencia desde pepino dulce hasta tomate es un interrogante de gran interés, porque es uno de los virus emergentes más recientes y de gran importancia económica. Para la emergencia de PepMV en tomate, se recolectaron muestras de tomate silvestre procedentes del sur de Perú, se analizó la presencia y diversidad de aislados de PepMV y se caracterizaron tanto biológicamente (gama de huéspedes), como genéticamente (secuencias genomicas). Se han descrito en diferentes regiones del mundo aislados de PMMoV que han adquirido la capacidad de infectar variedades previamente resistentes de pimiento (Capsicum spp), es decir, un típico caso de emergencia de virus que implica la ampliación de su gama de huéspedes y un aumento de patogenicidad. Esto tiene gran interés, ya que compromete el uso de variedades resistentes obtenidas por mejora genética, que es la forma de control de virus más eficaz que existe. Para estudiar la emergencia de genotipos altamente patogénicos de PMMoV, se analizaron clones biológicos de PMMoV procedentes de aislados de campo cuya patogenicidad era conocida (P1,2) y por mutagénesis se les aumentó la patogenicidad (P1,2,3 y P1,2,3,4), introduciendo las mutaciones descritas como responsables de estos fenotipos. Se analizó si el aumento de la patogenicidad conlleva un compromiso en la eficacia biológica de los genotipos de PMMoV. Para ello se evaluaron diferentes componentes de la eficacia biológica del virus en diferentes huéspedes con distintos alelos de resistencia. Los resultados de esta tesis demuestran: i). El potencial de las plantas silvestres como reservorios de virus emergentes, en este caso tomates silvestres del sur de Perú, así como la existencia en estas plantas de aislados de PepMV de una nueva cepa no descrita que llamamos PES. ii) El aumento de la gama de huéspedes no es una condición estricta para la emergencia de los virus de plantas. iii) La adaptación es el mecanismo más probable en la emergencia de PepMV en tomate cultivado. iv) El aumento de la patogenicidad tiene un efecto pleiotrópico en distintos componentes de la eficacia biológica, así mismo el signo y magnitud de este efecto dependerá del genotipo del virus, del huésped y de la interacción de estos factores. ABSTRACT host Pathogens have evolved strategies to survive in their environment, infecting their hosts, multiplying inside them and being transmitted to other hosts. All of these components form part of the pathogen fitness, and allow them to be the cause of infectious diseases in humans, animals, and plants. The infection process produces negative effects on the host fitness and the effects severity will depend on the pathogen virulence. On the other hand, hosts have developed response mechanisms against pathogens such as resistance, which reduces the growth of pathogens, or tolerance, which decreases the negative effects of infection. T he se responses of s to infection cause negative effects on the pathogen fitness, acting as a selective pressure on its population. If the selective pressures on pathogens va ry according to the host s , probably one pathogen cannot increase its fitness in different hosts and will be more adapted to one host and less to another, decreasing its host range. This means that the adaptation of one pathogen to different hosts , will be often limited by different trade - off components of biological effectiveness of pathogen. Nowadays , trade - off evidence of pathogen adaptation to different hosts is not extensive, in relation with plant viruses. In last decades, an increase in the incidence of new or previously detected viruses has been described, causing infectious diseases with increased severity and/or different pathogenicity, such as the hosts infection previously resistants. This is known as the emergence of infectious diseases and is caused by emerging pathogens that come from a reservoir host where they are adapted. The hosts which act as reservoirs can be wild plants, that often have few symptoms or very mild , despite of being infected with different viruses, and being found in ecosystems with little or any human intervention. The study of ecological and biological factors , acting in the process of the infectious diseases emergence will help to understand its causes to create strategies for its prevention and control. Viruses are the main causative pathogens of the infectious diseases emergence in humans, animals and plants, and a good model to understand the emergency processes. Likewise, plants in contrast to animals are easy host to handle and viruses that affect them, safer for laboratory work than viruses of humans and animals, another models used in research. Therefore, the interaction plant-virus is a good experimental model for the study of the infectious diseases emergence. The study of virus emergence in plants also has a particular interest, because the viruses can cause economic losses in agricultural crops and threaten the resistance durability of improved plants, it suppose a risk for food security with significant impacts on society, comparable with infectious diseases of humans and domestic animals. To become an emerging pathogen, a virus must jump first from its reservoir host to a new host, then adapt to a new host until the infection within the population becomes independent from the reservoir, and finally must change its epidemiology. In this study, the emergence of pepino mosaic virus (PepMV) in tomato, was selected as experimental model to study the emergence of a virus in a new host specie, as well as the infections of different genotypes of pepper mild mottle virus (PMMoV) in pepper, to study the emergence of a virus that increases its pathogenicity in a previously resistant host. The study of both Pathosystems increased our knowledge about the ecological and evolutionary factors in the two first phases of the emergence of viral diseases in plants. The PepMV is an emerging pathogen in tomato (Solanum lycopersicum L.) in the world, which was first described in 1980 by infecting pepino (Solanum muricatum L.) in Peru, and almost after a decade caused an epidemic in tomato crops in Netherlands. The introduction to Europe was possibly through infected tomato seeds from Peru, and from then have been described new isolates that are grouped in four strains (EU, LP, CH2, US1) that infect tomato. However, the process of its emergence from pepino up tomato is a very interesting question, because it is one of the newest emerging viruses and economically important. For the PepMV emergence in tomato, wild tomato samples from southern Peru were collected, and the presence and diversity of PepMV isolates were analyzed and characterized at biological (host range) and genetics (genomic sequences) levels. Isolates from PMMoV have been described in different world regions which have acquired the ability to infect pepper varieties that were previously resistants (Capsicum spp), it means, a typical case of virus emergence which involves the host range extension and an increased pathogenicity. This is of great interest due to involve the use of resistant varieties obtained by breeding, which is the most effective way to control virus. To study the emergence of highly pathogenic genotypes of PMMoV, biological clones from field isolates whose pathogenicity was known were analyzed (P1,2) and by mutagenesis we increased its pathogenicity (P1,2,3 and P1,2, 3,4), introducing the mutations described as responsible for these phenotypes. We analyzed whether the increased pathogenicity involves a trade-off in fitness of PMMoV genotypes. For this aim, different components of virus fitness in different hosts with several resistance alleles were evaluated. The results of this thesis show: i). The potential of wild plants as reservoirs of emerging viruses, in this case wild tomatoes in southern Peru, and the existence in these plants of PepMV isolates of a new undescribed strain that we call PES. ii) The host range expansion is not a strict condition for the plant virus emergence. iii) The adaptation is the most likely mechanism in the PepMV emergence in cultivated tomato. iv) The increased pathogenicity has a pleiotropic effect on several fitness components, besides the sign and magnitude of this effect depends on the virus genotype, the host and the interaction of both.

Sofrimento e Adaptação: Aspectos Sociais e Psico-afetivos de Pacientes com Doença Periodontal Crônica

OS OBJETIVOS DESTE ESTUDO FORAM: CARACTERIZAR A POPULAÇÃO DE PACIENTES DE UMA CLÍNICA-ESCOLA; INVESTIGAR OS ASPECTOS PSICO-AFETIVOS ASSOCIADOS ÀS DOENÇAS PERIODONTAIS DESSES PACIENTES, ALÉM DOS RECURSOS DEFENSIVOS UTILIZADOS POR ELES. MÉTODO: LEVANTOU-SE DADOS SÓCIO-DEMOGRÁFICOS, DE SAÚDE GERAL E PERIODONTAL DE 789 PACIENTES ATENDIDOS NUM DEPARTAMENTO DE PERIODONTIA DE UMA CLÍNICA-ESCOLA DE ODONTOLOGIA, DADOS ESTES QUE CONSTITUÍRAM A ETAPA QUANTITATIVA DO ESTUDO. ESSA CARACTERIZAÇÃO FOI FEITA ATRAVÉS DE PLANILHAS ESPECIALMENTE ELABORADAS PARA A PESQUISA. A PARTIR DESSAS PLANILHAS, FOI SELECIONADA UMA SUB-AMOSTRA DE 273 PACIENTES QUE APRESENTARAM QUEIXAS EM TRÊS OU MAIS SISTEMAS ORGÂNICOS, ALÉM DA QUEIXA PERIODONTAL, OS QUAIS FORAM DENOMINADOS DE PACIENTES POLI-QUEIXOSOS. UMA TERCEIRA SUB-AMOSTRA INTEGROU 59 PACIENTES POLI-QUEIXOSOS, DIAGNOSTICADOS COM DOENÇA LEVE A MODERADA OU LEVE A SEVERA. DESSES PACIENTES, TRÊS FORAM ENTREVISTADOS E INTEGRARAM A AMOSTRA DA ETAPA QUALITATIVA DA PESQUISA. OS RESULTADOS INDICARAM QUE ENTRE PACIENTES POLI-QUEIXOSOS NÃO FOI ENCONTRADA CORRELAÇÃO SIGNIFICATIVA ENTRE DOENÇA PERIODONTAL LEVE A MODERADA OU LEVE A SEVERA COM GÊNERO, IDADE, ESTADO CIVIL, GRAU DE INSTRUÇÃO OU ATIVIDADE LABORAL. TAMBÉM NÃO HOUVE RELAÇÃO SIGNIFICATIVA QUANTO À PRESENÇA DE TABAGISMO, BRUXISMO, ONICOFAGIA E XEROSTOMIA. VERIFICAMOS QUE A DOENÇA PERIODONTAL CRÔNICA TEM SUAS ORIGENS NAS RELAÇÕES OBJETAIS DA MAIS TENRA INFÂNCIA E QUE AS ANSIEDADES ESQUIZO-PARANÓIDES QUE CARACTERIZAM ESSAS PRIMEIRAS RELAÇÕES, CONTINUAM PERMEANDO AS RELAÇÕES DURANTE TODA A VIDA DAS PACIENTES. COMO OS RECURSOS DEFENSIVOS UTILIZADOS SÃO PSIQUICAMENTE POUCO EVOLUÍDOS, O EQUILÍBRIO, A HOMEOSTASE É ENCONTRADA NA DOENÇA. CONCLUÍMOS QUE A DINÂMICA INTRA-PSÍQUICA PODE ESTAR ASSOCIADA NÃO SÓ À DOENÇA PERIODONTAL, MAS TAMBÉM AO ESTADO DE SAÚDE GERAL DESSES PACIENTES.

Sofrimento e Adaptação: Aspectos Sociais e Psico-afetivos de Pacientes com Doença Periodontal Crônica

OS OBJETIVOS DESTE ESTUDO FORAM: CARACTERIZAR A POPULAÇÃO DE PACIENTES DE UMA CLÍNICA-ESCOLA; INVESTIGAR OS ASPECTOS PSICO-AFETIVOS ASSOCIADOS ÀS DOENÇAS PERIODONTAIS DESSES PACIENTES, ALÉM DOS RECURSOS DEFENSIVOS UTILIZADOS POR ELES. MÉTODO: LEVANTOU-SE DADOS SÓCIO-DEMOGRÁFICOS, DE SAÚDE GERAL E PERIODONTAL DE 789 PACIENTES ATENDIDOS NUM DEPARTAMENTO DE PERIODONTIA DE UMA CLÍNICA-ESCOLA DE ODONTOLOGIA, DADOS ESTES QUE CONSTITUÍRAM A ETAPA QUANTITATIVA DO ESTUDO. ESSA CARACTERIZAÇÃO FOI FEITA ATRAVÉS DE PLANILHAS ESPECIALMENTE ELABORADAS PARA A PESQUISA. A PARTIR DESSAS PLANILHAS, FOI SELECIONADA UMA SUB-AMOSTRA DE 273 PACIENTES QUE APRESENTARAM QUEIXAS EM TRÊS OU MAIS SISTEMAS ORGÂNICOS, ALÉM DA QUEIXA PERIODONTAL, OS QUAIS FORAM DENOMINADOS DE PACIENTES POLI-QUEIXOSOS. UMA TERCEIRA SUB-AMOSTRA INTEGROU 59 PACIENTES POLI-QUEIXOSOS, DIAGNOSTICADOS COM DOENÇA LEVE A MODERADA OU LEVE A SEVERA. DESSES PACIENTES, TRÊS FORAM ENTREVISTADOS E INTEGRARAM A AMOSTRA DA ETAPA QUALITATIVA DA PESQUISA. OS RESULTADOS INDICARAM QUE ENTRE PACIENTES POLI-QUEIXOSOS NÃO FOI ENCONTRADA CORRELAÇÃO SIGNIFICATIVA ENTRE DOENÇA PERIODONTAL LEVE A MODERADA OU LEVE A SEVERA COM GÊNERO, IDADE, ESTADO CIVIL, GRAU DE INSTRUÇÃO OU ATIVIDADE LABORAL. TAMBÉM NÃO HOUVE RELAÇÃO SIGNIFICATIVA QUANTO À PRESENÇA DE TABAGISMO, BRUXISMO, ONICOFAGIA E XEROSTOMIA. VERIFICAMOS QUE A DOENÇA PERIODONTAL CRÔNICA TEM SUAS ORIGENS NAS RELAÇÕES OBJETAIS DA MAIS TENRA INFÂNCIA E QUE AS ANSIEDADES ESQUIZO-PARANÓIDES QUE CARACTERIZAM ESSAS PRIMEIRAS RELAÇÕES, CONTINUAM PERMEANDO AS RELAÇÕES DURANTE TODA A VIDA DAS PACIENTES. COMO OS RECURSOS DEFENSIVOS UTILIZADOS SÃO PSIQUICAMENTE POUCO EVOLUÍDOS, O EQUILÍBRIO, A HOMEOSTASE É ENCONTRADA NA DOENÇA. CONCLUÍMOS QUE A DINÂMICA INTRA-PSÍQUICA PODE ESTAR ASSOCIADA NÃO SÓ À DOENÇA PERIODONTAL, MAS TAMBÉM AO ESTADO DE SAÚDE GERAL DESSES PACIENTES.

Superoxide-mediated clastogenesis and anticlastogenic effects of exogenous superoxide dismutase

Superoxide-mediated clastogenesis is characteristic for various chronic inflammatory diseases with autoimmune reactions and probably plays a role in radiation-induced clastogenesis and in the congenital breakage syndromes. It is consistently prevented by exogenous superoxide dismutase (SOD), but not by heat-inactivated SOD, indicating that the anticlastogenic effect is related to the catalytic function of the enzyme. Increased superoxide production by activated monocytes/macrophages is followed by release of more long-lived metabolites, so-called clastogenic factors, which contain lipid peroxidation products, unusual nucleotides of inosine, and cytokines such as tumor necrosis factor α. Since these components are not only clastogenic, but can stimulate further superoxide production by monocytes and neutrophils, the genotoxic effects are self-sustaining. It is shown here that anticlastogenic effects of exogenous SOD are preserved despite extensive washing of the cells and removal of all extracellular SOD. Using flow cytometry and confocal laser microscopy, rapid adherence of the fluorescently labeled enzyme to the cell surface could be observed with slow uptake into the cell during the following hours. The degree of labeling was concentration and time dependent. It was most important for monocytes, compared with lymphocytes, neutrophils, and fibroblasts. The cytochrome c assay showed significantly diminished O2− production by monocytes, pretreated with SOD and washed thereafter. The preferential and rapid binding of SOD to monocytes may be of importance not only for the superoxide-mediated genotoxic effects, described above, but also from a therapeutic standpoint. It can explain the observation that beneficial effects of injected SOD lasted for weeks and months despite rapid clearance of the enzyme from the blood stream according to pharmacodynamic studies.

Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29

Objective: To establish whether fetal growth rate (as distinct from size at birth) is associated with mortality from ischaemic heart disease.