Epidemia midiática: produção de sentidos e configuração social da febre amarela na cobertura jornalística, 2007-2008

O objetivo deste artigo, situado no campo da comunicação em saúde, é analisar os sentidos atribuídos discursivamente à febre amarela silvestre durante a cobertura jornalística da epizootia da doença, ocorrida no Brasil no verão 2007-2008. Utilizando o referencial teórico das práticas discursivas e da produção de sentidos no cotidiano e as hipóteses de agendamento (agenda-setting) e enquadramento (framing) da notícia, foram analisadas todas as matérias sobre febre amarela veiculadas pelo jornal Folha de S. Paulo, no período de 21 de dezembro de 2007 a 29 de fevereiro de 2008, e todos os documentos oficiais sobre a epizootia emitidos pela autoridade brasileira de saúde pública entre 3 de janeiro e 28 de fevereiro de 2008. Os achados indicam que as estratégias discursivas da cobertura jornalística relativizaram o discurso da autoridade de saúde pública; priorizaram a divulgação do número de casos; enfatizaram a vacinação como o limite entre a vida e a morte, omitindo riscos do uso indiscriminado do imunobiológico; e propagaram a iminência de uma epidemia de febre amarela de grandes proporções. Essas estratégias deram novos sentidos à doença, deslocando o evento de sua forma silvestre, espacialmente restrita e de gravidade limitada, para a urbana, de caráter epidêmico e potencialmente mais grave. Secundariamente, o estudo permitiu identificar os impactos desse discurso midiático sobre o sistema nacional de imunização e os riscos a que a população foi exposta em função dos sentidos produzidos: em 2008, foram registrados 8 casos de reação grave à vacina, dos quais 6 foram a óbito.

A stochastic spatially structured epidemic model with diffusive processes

We developed a stochastic lattice model to describe the vector-borne disease (like yellow fever or dengue). The model is spatially structured and its dynamical rules take into account the diffusion of vectors. We consider a bipartite lattice, forming a sub-lattice of human and another occupied by mosquitoes. At each site of lattice we associate a stochastic variable that describes the occupation and the health state of a single individual (mosquito or human). The process of disease transmission in the human population follows a similar dynamic of the Susceptible-Infected-Recovered model (SIR), while the disease transmission in the mosquito population has an analogous dynamic of the Susceptible-Infected-Susceptible model (SIS) with mosquitos diffusion. The occurrence of an epidemic is directly related to the conditional probability of occurrence of infected mosquitoes (human) in the presence of susceptible human (mosquitoes) on neighborhood. The probability of diffusion of mosquitoes can facilitate the formation of pairs Susceptible-Infected enabling an increase in the size of the epidemic. Using an asynchronous dynamic update, we study the disease transmission in a population initially formed by susceptible individuals due to the introduction of a single mosquito (human) infected. We find that this model exhibits a continuous phase transition related to the existence or non-existence of an epidemic. By means of mean field approximations and Monte Carlo simulations we investigate the epidemic threshold and the phase diagram in terms of the diffusion probability and the infection probability.

Molecular mechanisms involved in the pathogenesis of beet soil-borne viruses.

The genus Benyvirus includes the most important and widespread sugar beet viruses transmitted through the soil by the plasmodiophorid Polymyxa betae. In particular Beet necrotic yellow vein virus (BNYVV), the leading infectious agent that affects sugar beet, causes an abnormal rootlet proliferation known as rhizomania. Beet soil-borne mosaic virus (BSBMV) is widely distributed in the United States and, up to date has not been reported in others countries. My PhD project aims to investigate molecular interactions between BNYVV and BSBMV and the mechanisms involved in the pathogenesis of these viruses. BNYVV full-length infectious cDNA clones were available as well as full-length cDNA clones of BSBMV RNA-1, -2, -3 and -4. Handling of these cDNA clones in order to produce in vitro infectious transcripts need sensitive and expensive steps, so I developed agroclones of BNYVV and BSBMV RNAs, as well as viral replicons allowing the expression of different proteins. Chenopodium quinoa and Nicotiana benthamiana plants have been infected with in vitro transcripts and agroclones to investigate the interaction between BNYVV and BSBMV RNA-1 and -2 and the behavior of artificial viral chimeras. Simultaneously I characterized BSBMV p14 and demonstrated that it is a suppressor of post-transcriptional gene silencing sharing common features with BNYVV p14.

Modeling Techniques for the High-Resolution Interpretation of Cryo-Electron Microscopy Reconstructions

Essential biological processes are governed by organized, dynamic interactions between multiple biomolecular systems. Complexes are thus formed to enable the biological function and get dissembled as the process is completed. Examples of such processes include the translation of the messenger RNA into protein by the ribosome, the folding of proteins by chaperonins or the entry of viruses in host cells. Understanding these fundamental processes by characterizing the molecular mechanisms that enable then, would allow the (better) design of therapies and drugs. Such molecular mechanisms may be revealed trough the structural elucidation of the biomolecular assemblies at the core of these processes. Various experimental techniques may be applied to investigate the molecular architecture of biomolecular assemblies. High-resolution techniques, such as X-ray crystallography, may solve the atomic structure of the system, but are typically constrained to biomolecules of reduced flexibility and dimensions. In particular, X-ray crystallography requires the sample to form a three dimensional (3D) crystal lattice which is technically di‑cult, if not impossible, to obtain, especially for large, dynamic systems. Often these techniques solve the structure of the different constituent components within the assembly, but encounter difficulties when investigating the entire system. On the other hand, imaging techniques, such as cryo-electron microscopy (cryo-EM), are able to depict large systems in near-native environment, without requiring the formation of crystals. The structures solved by cryo-EM cover a wide range of resolutions, from very low level of detail where only the overall shape of the system is visible, to high-resolution that approach, but not yet reach, atomic level of detail. In this dissertation, several modeling methods are introduced to either integrate cryo-EM datasets with structural data from X-ray crystallography, or to directly interpret the cryo-EM reconstruction. Such computational techniques were developed with the goal of creating an atomic model for the cryo-EM data. The low-resolution reconstructions lack the level of detail to permit a direct atomic interpretation, i.e. one cannot reliably locate the atoms or amino-acid residues within the structure obtained by cryo-EM. Thereby one needs to consider additional information, for example, structural data from other sources such as X-ray crystallography, in order to enable such a high-resolution interpretation. Modeling techniques are thus developed to integrate the structural data from the different biophysical sources, examples including the work described in the manuscript I and II of this dissertation. At intermediate and high-resolution, cryo-EM reconstructions depict consistent 3D folds such as tubular features which in general correspond to alpha-helices. Such features can be annotated and later on used to build the atomic model of the system, see manuscript III as alternative. Three manuscripts are presented as part of the PhD dissertation, each introducing a computational technique that facilitates the interpretation of cryo-EM reconstructions. The first manuscript is an application paper that describes a heuristics to generate the atomic model for the protein envelope of the Rift Valley fever virus. The second manuscript introduces the evolutionary tabu search strategies to enable the integration of multiple component atomic structures with the cryo-EM map of their assembly. Finally, the third manuscript develops further the latter technique and apply it to annotate consistent 3D patterns in intermediate-resolution cryo-EM reconstructions. The first manuscript, titled An assembly model for Rift Valley fever virus, was submitted for publication in the Journal of Molecular Biology. The cryo-EM structure of the Rift Valley fever virus was previously solved at 27Å-resolution by Dr. Freiberg and collaborators. Such reconstruction shows the overall shape of the virus envelope, yet the reduced level of detail prevents the direct atomic interpretation. High-resolution structures are not yet available for the entire virus nor for the two different component glycoproteins that form its envelope. However, homology models may be generated for these glycoproteins based on similar structures that are available at atomic resolutions. The manuscript presents the steps required to identify an atomic model of the entire virus envelope, based on the low-resolution cryo-EM map of the envelope and the homology models of the two glycoproteins. Starting with the results of the exhaustive search to place the two glycoproteins, the model is built iterative by running multiple multi-body refinements to hierarchically generate models for the different regions of the envelope. The generated atomic model is supported by prior knowledge regarding virus biology and contains valuable information about the molecular architecture of the system. It provides the basis for further investigations seeking to reveal different processes in which the virus is involved such as assembly or fusion. The second manuscript was recently published in the of Journal of Structural Biology (doi:10.1016/j.jsb.2009.12.028) under the title Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions. This manuscript introduces the evolutionary tabu search strategies applied to enable a multi-body registration. This technique is a hybrid approach that combines a genetic algorithm with a tabu search strategy to promote the proper exploration of the high-dimensional search space. Similar to the Rift Valley fever virus, it is common that the structure of a large multi-component assembly is available at low-resolution from cryo-EM, while high-resolution structures are solved for the different components but lack for the entire system. Evolutionary tabu search strategies enable the building of an atomic model for the entire system by considering simultaneously the different components. Such registration indirectly introduces spatial constrains as all components need to be placed within the assembly, enabling the proper docked in the low-resolution map of the entire assembly. Along with the method description, the manuscript covers the validation, presenting the benefit of the technique in both synthetic and experimental test cases. Such approach successfully docked multiple components up to resolutions of 40Å. The third manuscript is entitled Evolutionary Bidirectional Expansion for the Annotation of Alpha Helices in Electron Cryo-Microscopy Reconstructions and was submitted for publication in the Journal of Structural Biology. The modeling approach described in this manuscript applies the evolutionary tabu search strategies in combination with the bidirectional expansion to annotate secondary structure elements in intermediate resolution cryo-EM reconstructions. In particular, secondary structure elements such as alpha helices show consistent patterns in cryo-EM data, and are visible as rod-like patterns of high density. The evolutionary tabu search strategy is applied to identify the placement of the different alpha helices, while the bidirectional expansion characterizes their length and curvature. The manuscript presents the validation of the approach at resolutions ranging between 6 and 14Å, a level of detail where alpha helices are visible. Up to resolution of 12 Å, the method measures sensitivities between 70-100% as estimated in experimental test cases, i.e. 70-100% of the alpha-helices were correctly predicted in an automatic manner in the experimental data. The three manuscripts presented in this PhD dissertation cover different computation methods for the integration and interpretation of cryo-EM reconstructions. The methods were developed in the molecular modeling software Sculptor (http://sculptor.biomachina.org) and are available for the scientific community interested in the multi-resolution modeling of cryo-EM data. The work spans a wide range of resolution covering multi-body refinement and registration at low-resolution along with annotation of consistent patterns at high-resolution. Such methods are essential for the modeling of cryo-EM data, and may be applied in other fields where similar spatial problems are encountered, such as medical imaging.

Eight novel families of miniature inverted repeat transposable elements in the African malaria mosquito, Anopheles gambiae

Eight novel families of miniature inverted repeat transposable elements (MITEs) were discovered in the African malaria mosquito, Anopheles gambiae, by using new software designed to rapidly identify MITE-like sequences based on their structural characteristics. Divergent subfamilies have been found in two families. Past mobility was demonstrated by evidence of MITE insertions that resulted in the duplication of specific TA, TAA, or 8-bp targets. Some of these MITEs share the same target duplications and similar terminal sequences with MITEs and other DNA transposons in human and other organisms. MITEs in A. gambiae range from 40 to 1340 copies per genome, much less abundant than MITEs in the yellow fever mosquito, Aedes aegypti. Statistical analyses suggest that most A. gambiae MITEs are in highly AT-rich regions, many of which are closely associated with each other. The analyses of these novel MITEs underscored interesting questions regarding their diversity, origin, evolution, and relationships to the host genomes. The discovery of diverse families of MITEs in A. gambiae has important practical implications in light of current efforts to control malaria by replacing vector mosquitoes with genetically modified refractory mosquitoes. Finally, the systematic approach to rapidly identify novel MITEs should have broad applications for the analysis of the ever-growing sequence databases of a wide range of organisms.

Vitamin B12 and hepatitis C: Molecular biology and human pathology

Cobalamins are stored in high concentrations in the human liver and thus are available to participate in the regulation of hepatotropic virus functions. We show that cyanocobalamin (vitamin B12) inhibited the HCV internal ribosome entry site (IRES)-dependent translation of a reporter gene in vitro in a dose-dependent manner without significantly affecting the cap-dependent mechanism. Vitamin B12 failed to inhibit translation by IRES elements from encephalomyocarditis virus (EMCV) or classical swine fever virus (CSFV). We also demonstrate a relationship between the total cobalamin concentration in human sera and HCV viral load (a measure of viral replication in the host). The mean viral load was two orders of magnitude greater when the serum cobalamin concentration was above 200 pM (P < 0.003), suggesting that the total cobalamin concentration in an HCV-infected liver is biologically significant in HCV replication.

Student lectures notes on chemistry and materia medica, and medical recipes, of Lyman Spalding, 1795-1799 (inclusive)

Contains notes taken by Harvard student Lyman Spalding during eleven chemistry lectures delivered by Harvard Professor Aaron Dexter (1750-1829) in the fall of 1795 and recipes prepared and used by Spalding in his medical practice in 1797. The recipes include elixir vitriol, containing liquor, Jamaica pepper, cinnamon, and ginger, and an electuary for a cough, containing oxymel squills (sea onion in honey), licorice, antimonium tartaricum potash (a compound of the chemical element antimony and a potassium-containing salt), and opium. The volume also contains writings about chemistry by Spalding, some of which appear transcribed from published sources, in undated entries, and a diary entry from 1799 regarding an experiment with water.

Student lecture notes on the Theory & Practice of Physic, and patient case histories, of Lyman Spalding, 1795-1799 (inclusive)

Contains notes taken by Harvard student Lyman Spalding from lectures delivered by Hersey Professor of the Theory and Practice of Physic Benjamin Waterhouse (1754-1846) in 1795. The notes cover the history of medicine, theories of contemporary physicians like Herman Boerhaave, William Cullen, and John Brown, and topics like fetal growth, digestion, and circulation. The volume also contains six pages of patient case notes from Spalding’s medical practice in Walpole, New Hampshire, in 1799, which detail the patients’ symptoms and course of treatment he pursued. In the case of a young man who complained of pain in his breast following a wrestling match, Spalding bled him and prescribed a cathartic of soap and aloes. Spalding also operated on a man who cut off part of his ankle with an ax.

Student lecture notes on anatomy and surgery, and medical notes, of Lyman Spalding, 1795

Contains notes taken by Harvard student Lyman Spalding (1775-1821) from lectures on anatomy and surgery delivered by Harvard Professor John Warren (1753-1815) in 1795, as well a section entitled “Medical Observations,” which includes entries on “Vernal Debility,” or diseases occurring in the spring, and lung function. It is unclear if these are Spalding’s own writings or transcriptions from a published work. There is also text transcribed from “Elementa Medicinae,” published in 1780 by Scottish physician John Brown.

Student notes from medical lectures by Benjamin Rush, undated

The volumes contain student notes on a course of medical lectures given by Dr. Benjamin Rush (1746-1813) while he was Professor of the Institutes of Medicine and Clinical Practice at the University of Pennsylvania Medical School, likely in circa 1800-1813. The notes indicate Rush often referenced the works or teachings of contemporaries such as Scottish physicians William Cullen, John Brown, John Gregory, and Robert Whytt, and Dutch physician Herman Boerhaave. He frequently included anecdotes and case histories of his own patients, as well as those of other doctors, to illustrate his lecture topics. He also advised students to take notes on the lectures after they ended to allow them to focus on what they were hearing. Volume 1 includes notes on: physician conduct during visits to patients; human and animal physiology; voice and speech; the nervous system; the five senses; and faculties of the mind. Volume 2 includes notes on: food, the sources of appetite and thirst, and digestion; the lymphatic system; secretions; excretions; theories of nutrition; differences in the minds and bodies of women and men; reproduction; pathology; a table outlining the stages of disease production; “disease and the origin of moral and natural evil”; contagions; the role of food, drink, and clothing in producing disease; worms; hereditary diseases; predisposition to diseases; proximate causes of diseases; and pulmonary conditions. Volume 3 includes notes on: the pulse; therapeutics, such as emetics, sedatives, and digitalis, and treatment of various illnesses like pulmonary consumption, kidney disease, palsy, and rheumatism; diagnosis and prognosis of fever; treatment of intermitting fever; and epidemics including plague, smallpox, and yellow fever, with an emphasis on the yellow fever outbreaks in Philadelphia in 1793 and 1797.

Old family letters: copied from the originals for Alexander Biddle.

Mode of access: Internet.

Annual report ...

Also included in Rockefeller foundation. Annual report. 1927-1933 not issued separately.

Bulletin ...

Walter Wyman, surgeon-general, Public Health and Marine Hospital Service.

Minutes of the proceeds of the committee, appointed on the 14th September, 1793 /

First published 1794.

Annual report of the National Board of Health.

Report for 1884 printed without appendices.