BOLETIM ELETRÔNICO ABRASCO

Pesquisa em Atenção Primária à Saúde: como construir uma agenda para o Brasil? A Rede de Pesquisa em Atenção Primária à Saúde abriu seu terceiro fórum de debates sobre o tema "Pesquisa em Atenção Primária à Saúde: como construir uma agenda para o Brasil?". A partir da pauta proposta a Rede coloca três questões para reflexão: Considerando-se que a elaboração de uma agenda de pesquisa em APS deve buscar refletir a natureza e complexidade desse objeto, que eixos ou dimensões devem ser priorizados na pesquisa em APS e por quê?; Que iniciativas devem ser implementadas ou fortalecidas para impulsionar o desenvolvimento da pesquisa em APS e qual o protagonismo e tarefas da Rede de Pesquisa em APS nessa questão? e; Como melhorar a utilização dos resultados de pesquisa por gestores e profissionais no âmbito da APS?. O Fórum recebe contribuições até o dia 10 de maio, quando será realizado um debate online, das 16h às 17h, com as coordenadoras da atividade, Maria Guadalupe Medina e Rosana Aquino (Pesquisadoras do Instituto de Saúde Coletiva da Universidade Federal da Bahia, Coordenadoras do Programa Integrado de Pesquisa e Cooperação Técnica em Formação e Avaliação da Atenção Básica - GRAB). Saiba como participar clicando aqui.

Saúde Mental em pauta O coordenador do GT Saúde Mental da ABRASCO e do Laboratório de Estudos e Pesquisas em Saúde Mental e Atenção Psicossocial da Escola Nacional de Saúde Pública Sergio Arouca (Laps/ENSP), Paulo Amarante, um dos organizadores do projeto Loucos pela Diversidade e nome reconhecido no movimento de reforma psiquiátrica no Brasil é o entrevistado da primeira edição da revista eletrônica RapaDura. A entrevista, feita em vídeo, aborda temas como: a situação das instituições psiquiátricas, a forma como o Estado trata a questão e o conceito de alienação, Reforma Manicomial, o SUS, o mercado da saúde, entre outros temas. Confira a entrevista clicandoaqui.

Presidente da SBMFC concede entrevista à Rede de Pesquisa APS Gustavo Gusso, presidente da Sociedade Brasileira de Medicina de Família e Comunidade (SBMFC) é o entrevistado do mês de abril da Rede de Pesquisa em Atenção Primária à Saúde. Na entrevista Gusso fala sobre os pontos positivos e negativos do SUS, e da APS em particular, destacando seus principais avanços e a dificuldade importa pela contratação de profissionais (especialmente médicos), os desafios que enfrenta na presidência da SBMFC, a programação do 11° Congresso Brasileiro de Medicina de Família e as contribuições da Rede de Pesquisa em APS. Confira a entrevista clicando aqui.

´Semana da saúde´ no Senado tem 47 projetos em pauta Um total de 47 projetos pode fazer parte da "semana da saúde", esforço concentrado para votação de projetos da área definido pelo presidente do Senado, José Sarney, em conjunto com lideranças partidárias. A prevenção ao uso de drogas, a relação dos clientes com os planos de atendimento e o custeio e a organização da saúde são temas dominantes nas propostas. Mais detalhes aqui.

Fórum de Mobilização para Enfrentamento das Doenças Negligenciadas O Programa de Enfrentamento às Doenças Negligenciadas da Secretaria de Saúde do Governo de Pernambuco está promovendo o Fórum de Mobilização para Enfrentamento das Doenças Negligenciadas, no próximo dia 05 de maio, das 8h30 às 17h. O encontro tem como objetivo falar sobre o enfrentamento de doenças tropicais endêmicas que atingem a população de baixa renda: tracoma, doença de Chagas, hanseníase, filariose, esquistossomose, helmintíase e tuberculose e será realidado no Centro de Convenções da Universidade Federal de Pernambuco.

Seminário Internacional Rotas Críticas III: situações limite decorrentes de violências de Gênero O Seminário Internacional Rotas Críticas III: situações limite decorrentes de violências de gênero será realizado de 25 a 27 de maio, na Universidade Federal do Rio Grande do Sul. O encontro tem como público alvo a comunidade acadêmica e trabalhadores de saúde, segurança pública, educação, ação social, jurídicos e militantes de ONGs e movimentos sociais. O Seminário é uma promoção da UFRGS, através do Curso de Análise de Políticas e Sistemas de Saúde e do Programa de Pós-graduação em Enfermagem, conta com apoio do CNPq é tem caráter gratuito. Veja a programação detalhada clicando aqui.

10th International Conference on Urban Health We are pleased to announce the call for abstracts for the 10th International Conference on Urban Health (ICUH), to be held November 1–5, 2011 in Belo Horizonte, Brazil. The abstract deadline is June 30th, 2011, and applicants will be notified of the final decisions on their submissions by July 30th.  The website for the Conference is www.icuh2011.com. The principal theme to be addressed will be urban health action toward equity, with special interest in the urban context, its metrics, and interventions. The conference will examine how institutions and governments can develop and implement interventions that improve health equity, based upon the urban health evidence. These issues will be examined in a multitude of sectors, such as climate change, air pollution, physical activity, health services, violence and security, transportation and injuries, housing and infrastructure, neighborhoods and the urban environment, reproductive and maternal child health, the social determinants of health, substance use and vulnerable populations, and still others. The meeting is being jointly organized by the School of Medicine of the Federal University of Minas Gerais (UFMG), the Belo Horizonte Observatory for Urban Health, and the International Society for Urban Health. The Observatory, a partnership between UFMG and the Belo Horizonte Municipality, has made the city a model for efforts to increase health equity in the urban setting. Founded in 2002, its mission is to build workforce capacity in population health research and to conduct urban-themed studies that can drive planning for improving urban health.

Publicações e oportunidades Clique nos links a seguir e confira as publicações e oportunidades da semana.

Get a Whiff of This: Low-Cost Sensor Can Diagnose Bacterial Infections

ScienceDaily (Apr. 27, 2011) — Bacterial infections really stink. And that could be the key to a fast diagnosis. Researchers have demonstrated a quick, simple method to identify infectious bacteria by smell using a low-cost array of printed pigments as a chemical sensor. Led by University of Illinois chemistry professor Ken Suslick, the team published its results in the Journal of the American Chemical Society.

The researchers tested their array on ten common infectious bacteria. The color changes of the sensor array show what kind of bacteria is growing and even if they are antibiotic resistant. 

Hospitals have used blood cultures as the standard for identifying blood-borne bacterial infections for more than a century. While there have been some improvements in automating the process, the overall method has remained largely constant. Blood samples are incubated in vials for 24 to 48 hours, when a carbon dioxide sensor in the vials will signal the presence of bacteria. But after a culture is positive, doctors still need to identify which species and strain of bacteria is in the vial, a process that takes up to another day.

"The major problem with the clinical blood culturing is that it takes too long," said Suslick, the Marvin T. Schmidt professor of chemistry, who also is a professor of materials science and engineering and a member of the Beckman Institute for Advanced Science and Technology. "In 72 hours they may have diagnosed the problem, but the patient may already have died of sepsis."

While there has been some interest in using sophisticated spectroscopy or genetic methods for clinical diagnosis, Suslick's group focused on another distinctive characteristic: smell. Many experienced microbiologists can identify bacteria based on their aroma. Bacteria emit a complex mixture of chemicals as by-products of their metabolism. Each species of bacteria produces its own unique blend of gases, and even differing strains of the same species will have an aromatic "fingerprint."

An expert in chemical sensing, Suslick previously developed an artificial "nose" that can detect and identify poisonous gases, toxins and explosives in the air.

"Our approach to this problem has been to think of bacteria as simply micron-sized chemical factories whose exhaust is not regulated by the EPA," Suslick said. "Our technology is now well-proven for detecting and distinguishing among different chemical odorants, so applying it to bacteria was not much of a stretch."

The artificial nose is an array of 36 cross-reactive pigment dots that change color when they sense chemicals in the air. The researchers spread blood samples on Petri dishes of a standard growth gel, attached an array to the inside of the lid of each dish, then inverted the dishes onto an ordinary flatbed scanner. Every 30 minutes, they scanned the arrays and recorded the color changes in each dot. The pattern of color change over time is unique to each bacterium.

"The progression of the pattern change is part of the diagnosis of which bacteria it is," Suslick said. "It's like time-lapse photography. You're not looking just at a single frame, you're looking at the motion of the frames over time."

In only a few hours, the array not only confirms the presence of bacteria, but identifies a specific species and strain. It even can recognize antibiotic resistance -- a key factor in treatment decisions.

In the paper, the researchers showed that they could identify 10 of the most common disease-causing bacteria, including the hard-to-kill hospital infection methicillin-resistant Staphylococcus aureus (MRSA), with 98.8 percent accuracy. However, Suslick believes the array could be used to diagnose a much wider variety of infections.

"We don't have an upper limit. We haven't yet found any bacteria that we can't detect and distinguish from other bacteria," he said. "We picked out a sampling of human pathogenic bacteria as a starting point."

Given their broad sensitivity, the chemical-sensing arrays also could enable breath diagnosis for a number of conditions. Medical researchers at other institutions have already performed studies using Suslick's arrays to diagnose sinus infections and to screen for lung cancer.

Next, the team is working on integrating the arrays with vials of liquid growth medium, which is a faster culturing agent and more common in clinical practice than Petri dishes. They have also improved the pigments to be more stable, more sensitive and easier to print. The device company iSense, which Suslick co-founded, is commercializing the array technology for clinical use.

The National Institutes of Health supported this research through the Genes, Environment and Health Initiative. Co-authors of the paper included professor James Carey, of the National University of Kaoshiung; U. of I. microbiology professor James Imlay; research specialist Karin Imlay; and co-workers Crystal Ingison, Jennifer Ponder, Avijit Sen and Aaron Wittrig.

Scientists Identify Genetic Risk for Major Depression

ScienceDaily (Apr. 27, 2011) — A new study reveals a novel gene associated with major depression. The research, published in the April 28 issue of the journal Neuron, suggests a previously unrecognized mechanism for major depression and may guide future therapeutic strategies for this debilitating mood disorder.

Depressive patients carrying the risk allele show volume reduction in certain regions of the hippocampus. 

Major depression is a psychiatric disorder that is responsible for a substantial loss in work productivity and can even lead to suicide in some individuals. "Current treatments for major depression are indispensible but their clinical efficacy is still unsatisfactory, as reflected by high rates of treatment resistance and side effects," explains study author Dr. Martin A. Kohli from the Max Planck Institute of Psychiatry in Munich, Germany. "Identification of mechanisms causing depression is pertinent for discovery of better antidepressants."

While is likely that a combination of genetic and environmental risk factors contribute to major depression, identification of risk-conferring genes has been challenging due to the complexity of the genetics and the considerable environmental factors associated with the disease. Dr. Kohli and colleagues performed a stringent genome-wide association study of patients diagnosed with major depression and matched control subjects with no history of psychiatric illness. They identified SLC6A15, a gene that codes for a neuronal amino acid transporter protein, as a novel susceptibility gene for major depression. The finding was confirmed in an expanded study examining over 15,000 individuals.

The researchers examined the functional relevance of the genetic association between SLC6A15 and major depression. Already nondepressed subjects carrying the risk-conferring genetic variants showed lower expression of SLC6A15 in the hippocampus, a brain region implicated in major depression. Moreover, using human brain imaging, risk variant carriers with a positive life history of major depression showed smaller hippocampi. Finally, in a mouse model, lower hippocampal SLC6A15 expression was linked to the effects of chronic social stress, a proven risk factor for depression.

The authors suggest that reduced SLC6A15 expression might lead to perturbation of neuronal circuits related to susceptibility for major depression. "Our results support the notion that lower SLC6A15 expression, especially in the hippocampus, could increase an individual's stress susceptibility by altering neuronal integrity and excitatory neurotransmission in this key brain region," says senior author Dr. Elisabeth B. Binder. "Because SLC6A15 appears amenable to drug targeting, our results may incite the discovery of a novel class of antidepressant drugs."

Versatility of Stem Cells Controlled by Alliances, Competitions of Proteins

ScienceDaily (Apr. 27, 2011) — Because they can change into any other cell, stem cells are the subject of intense research, but how they "decide" to specialize, or differentiate, hasn't been understood. A new study using a unique technology shows that proteins must jostle and join behind the scenes to make it happen, as well as to restore flexibility to cells that already had made their choice.

More like globs of proteins Transcription factors may compete or cooperate within cells, producing complex bindings across hundreds of nucleotides, determing what kind of cells stem cells become. William Fairbrother, center, postdoctoral researcher Alec DeSimone and technician Luciana Ferraris analyzed hundreds of thousands of DNA letters and found previously unspotted patterns of protein interactions.

Like people with a big choice to make, stem cells have a process to "decide" whether to transform into a specific cell type or to stay flexible, a state that biologists call "pluripotency." Using a technology he invented, Brown researcher William Fairbrother and colleagues have discovered new molecular interactions in the process that will help regenerative medicine researchers better understand pluripotency.

In a paper published in advance online in the journal Genome Research, Fairbrother's team showed that different proteins called transcription factors compete and cooperate in the cells to produce complex bindings along crucial sequences of DNA. This game of molecular "capture the flag," played in teams and amid shifting alliances, appears to be a necessary part of what determines whether stem cells retain their pluripotency and whether specialized, or differentiated, cells can regain it.

In recent years scientists have reported spectacular successes in turning fully differentiated cells back into pluripotent stem cells, a process called reprogramming. But the animals derived from these cells often suffer higher rates of tumors and other problems, Fairbrother said. The reason may be because the complex details of the reprogramming process haven't been fully understood. He said there are many misconceptions about how reprogramming transcription factors interact with DNA.

"Most people think of a protein binding to DNA as a single, surgical thing where you have this isolated binding event," Fairbrother said. "But in fact we show that sometimes these binding events occur over hundreds of nucleotides so they seem more like great greasy globs of proteins that are forming. In addition, the proteins interact with each other, diversifying their function by appearing in complexes with with different partners at different places."

By employing a high-throughput, high-resolution binding assay that he's dubbed MEGAShift, Fairbrother and his colleagues, who include pathology researchers from the University of Utah School of Medicine, were able to analyze the interactions of several key transcription factors in a region of 316,000 letters of DNA with a resolution as low as 10 base pairs. Through hundreds of thousands of array measurements, lead authors Luciana Ferraris and Allan Stewart, Fairbrother, Alec DeSimone, and the other authors learned previously unspotted patterns of protein interactions.

"How do stem cells stay in the state where they can keep their options open?" Fairbrother said. "A key player is POU5F1. But what are the key players that could interact with it and modulate its function? We've developed technology to look at that question."

One of several findings in the paper concerned POU5F1 and its archrival, POU2F1, which binds to exactly the same eight-letter DNA sequence. Which protein binds to the sequence first influences whether a stem cell specializes or remains pluripotent. Experiments showed that a determining factor was a third protein called SOX2. SOX2 helped both proteins bind, but it helps POU2F1 more than POU5F1. In contrast, the team found that another player, NANOG, exclusively helps POU5F1.

"Who binds next to a protein is a determinant of who ends up binding to a sequence," Fairbrother said.

With support from the National Institutes of Health, Fairbrother's group is also applying MEGAShift to other questions, including how protein-protein interactions affect the formation of RNA-protein complexes, which can be even more complicated than binding DNA.

They will also look at the problem of narrowing the field of hundreds of genomic sequence variations that exist naturally in the population down to the real genetic "causal variants" of disease risk. MEGAShift can sort through which variants associated with disease result in an altered binding event that results in a clinical manifestation, such as diabetes or lupus.

In addition to Fairbrother, DeSimone, Ferraris and Stewart, other authors on the paper Matthew Gemberling at Brown, Dean Tantin at the University of Utah, and Jinsuk Kang also at the University of Utah.

The research was funded by the National Human Genome Research Institute.

Motor Protein May Offer Promise in Ovarian Cancer Treatment

ScienceDaily (Apr. 27, 2011) — A motor regulatory protein can block human ovarian tumor growth, leading to eventual cancer cell death and possible new therapies to treat the disease, according to Penn State College of Medicine researchers.

Among U.S. women, an estimated 21,880 new cases and 13,850 deaths occurred in 2010 from epithelial ovarian cancer, one of the most common forms of ovarian cancer and the most lethal gynecologic cancer in women.

Previously, Kathleen M. Mulder, Ph.D., professor, biochemistry and molecular biology, along with members of her laboratory, learned that km23-1 -- a protein -- is defective in nearly half of all ovarian cancer patients. In the current study, researchers induced over-expression of km23-1 in human ovarian cancer cells placed in mice, causing the cells to produce large amounts of the normal protein.

km23-1 is a subunit of dynein, a motor protein that transports cargo along paths in the cell called microtubules. The dynein motor has many jobs in the cell, including major roles in cell division.

"Although microtubule-binding agents, such as the drug paclitaxel, are being used in the treatment of ovarian cancer, drug resistance has significantly limited their efficacy," Mulder said. "It is critical to develop novel, targeted therapeutics for ovarian cancer. Motor protein regulatory agents may offer promise for providing improved efficacies with reduced side effects in the treatment of ovarian cancer and other human malignancies."

Nageswara Pulipati, Ph.D., postdoctoral fellow in Mulder's lab, said, "We used a method to cause the tumors to express high levels of normal km23-1, but only in the experimental group of mice. Compared to the control group, the tumors were much smaller when km23-1 was over-expressed."

Findings were reported online and will appear in an upcoming edition of The International Journal of Cancer.

"The dynein motor protein is needed to transport checkpoint proteins along the microtubules during mitosis. However, when km23-1 levels are high, at least one checkpoint protein, BubR1, is not transferred properly," said Qunyan Jin, M.D., research associate in Mulder's lab.

During the cell division process, several checkpoints exist where specific proteins put a hold on cell division until proper completion of a specific step can be verified. When km23-1 is over-expressed, a checkpoint is stalled during mitosis -- the stage in the cell division process that normally facilitates equal splitting of the chromosomes into two identical groups before the mother cell splits into two daughter cells.

"Normally, if everything is correct at this checkpoint, the cell then goes on to divide," Mulder said. "However, with the over-expression of km23-1, the checkpoint stays on and cell division does not proceed normally, which leads to a slow cell death."

Mulder and her lab team will now look at how the over-expression of km23-1 may be mimicked to target km23-1, using nanotechnology to deliver a drug to the cancer cells, and how this approach may possibly be used in humans.

This National Institutes of Health and the Department of Defense supported this work. Also contributing to this research were Xin Liu, Ph.D., Yan Zhao, Ph.D., Baodong Sun, M.D., Manoj K. Pandey, Ph.D., Jonathan P. Huber, Ph.D. and Wei Ding, Ph.D.

Strides Made in Understanding Amyotrophic Lateral Sclerosis

ScienceDaily (Apr. 27, 2011) — Brandeis researchers have made a significant advance in the effort to understand amyotrophic lateral sclerosis (ALS) by successfully reversing the toxicity of the mutated protein in the familial type of the disease.

These yeast cells are expressing human FUS/TLS (green spots) in cytosol, with blue stain of nucleus. 

Currently there is no cure or prevention for the disease, which affects nerve cells in the brain and the spinal cord. Most frequently referred to as Lou Gehrig's disease, after its most famous victim, ALS typically causes death due to respiratory paralysis within three to five years of onset. The only approved drug, Riluzole, can extend the lifespan of some patients by three months.

In a paper published on April 26 inPLoS Biology, the Pestko/Ringe laboratory reports success in blocking the lethal effects of the gene by placing several human genes into a yeast cell that shows many similar features to the disease-causing proteins.

Genes have been identified for many of the 10 percent of ALS cases that run in families. People with one of those mutant genes are likely to develop the disease. While a few of those genes might also contain mutations that increase risk for the more common forms of ALS, it's one of those genes, FUS/TLS, which got the attention of the Pesko/Ringe team.

"We started to work on this project when we learned that mutations of FUS/TLS gene were linked to familial ALS by our collaborators, Dr. Robert Brown's group, at the University of Massachusetts medical school," says Shulin Ju, a post-doctoral researcher and first author of the paper. The collaboration also includes members of Whitehead Institute for Biomedical Research, MIT, Harvard University, University of Rochester and the University of Pennsylvania.

Here is some of the biology and chemistry behind the research:

Post-mortem examinations of certain ALS victims show that the dying neurons contain clumps of the FUS/TLS protein. What's interesting, says Gregory A. Petsko, professor of chemistry and biochemistry, is where these inclusions are.

"Normally this protein lives in the nucleus of the cell, which is where the chromosomes are," says Petsko. "In this disease, it seems to move from the nucleus out into the cytoplasm of the cell, the main part, and that's where it forms the inclusions that are associated with the disease."

Petsko and Ringe's team wanted to study this process in an organism on which they could perform sophisticated genetic screenings and detailed biochemical experiments, which can not be done in human cells. So they chose yeast.

"It may seem kind of crazy to think of doing yeast experiments on a human neurologic disease, since yeast has no brain or spinal cord or any neurons at all," says Petsko, "But a yeast cell isn't that different from a typical human cell."

The team inserted the FUS/TLS gene into a yeast cell with the hope that it would create the same observable characteristics as the mutant protein does in a human cell. When they did, Petsko says, two remarkable things happened.

"First thing is that the human protein wasn't in the nucleus, it moved to the cytoplasm of the cell just like it did in the human disease -- and it formed inclusions," says Petsko. "The second thing is that it killed the yeast cell, so we got in yeast a pretty faithful replication of some of the features of the human disease caused by mutation of this gene."

The next step was to find out what part of the protein was necessary in order to keep it in the nucleus and what part was necessary to send it to the cytoplasm.

Petsko then asked, "If we started deleting sections of the protein could we force the protein to always be in the cytoplasm or always be in the nucleus?"

When they performed the experiment with yeast they found that the area of the gene where the disease-causing mutations occur was the area responsible for keeping it in the nucleus; when that area is mutated, the gene leaves the nucleus for the cytoplasm.

"We want to keep it in the nucleus but you can't do that with the mutants easily because the part responsible for keeping it in the nucleus has been destroyed by the mutation, which is why you have the disease," says Petsko.

They then asked whether they could prevent the yeast cells from being killed by this protein by placing some other protein inside.

In other words, Petsko says, could they find a protein that would rescue the cell from the toxicity of FUS/TLS?

By a series of genetic experiments described in the paper, they were able to identify several human genes which, when inserted along with FUS/TLS gene, rendered FUS/TLS protein no longer toxic to yeast. The cells survived.

"And then we got the surprise of our life," says Petsko. "When we looked at those cells, FUS/TLS protein was still in the cytoplasm, and still forming inclusions. In other words, we were able to eliminate the toxicity of the protein without sending it back to the nucleus."

What this told them was that aggregating and being in the cytoplasm didn't necessarily have to be toxic as long as the rescue protein that they found was introduced.

That, says Petsko, got them really excited, because "if you can do that with the expression with another human gene you could probably do that with a drug."