Health Meaning

An investigation concluded that the surgeon Paolo Macchiarini, famous for trachea transplantation of tissue engineering in more than a dozen people at fault scientist. The Karolinska Institute in Sweden, where Macchiarini is visiting professor, ordered the outside investigation in response to allegations by four researchers from the Institute and Karolinska University Hospital affiliated to Stockholm, where many of the transplants were performed.

The external investigator Bengt Gerdin, Emeritus Professor of Surgery at Uppsala University, presented his report (in Swedish), May 13 (The journal Svenska Dagbladet first reported the results of yesterday.)

The allegations made by the researchers involved Karolinska three surgeries performed at Karolinska for people who have a damaged trachea . One patient, described in an article The Lancet , survived for 2 years after receiving the artificial trachea, which incorporated human stem cells. Another patient survived for only two months. A third is still alive, but he was in intensive care at Karolinska since surgery in August 2012.

Gerdin said Science Insider that, in the relatively narrow definition of research misconduct Swedish law, his main task was to compare the data presented in six technical papers describing the laboratory and patient records to Institute and hospital. "There was information in the documents could not be found in the medical records," he said. The number of mismatches, Gerdin said, led him to conclude that there was "a systemic false statement of truth that will lead the reader to have a completely false impression of the success of the technique." Such misrepresentation is serious misconduct, he said.

science Insider has not been able to reach Macchiarini. He told Retraction Watch it could not comment until it had seen an English translation of the report.

The doctors who reported Macchiarini also alleged that he did not obtain proper authorization for surgery and failed to obtain informed consent from patients. These issues are of the right of Swedish health care rather than scientific misconduct regulations, Gerdin said that his report is not a judgment on the allegations. "I just listed the issues that I found a way that other authorities can take this over," he said. The Swedish Medical Products Agency referred the case to a prosecutor, they say it. (the Svenska Dagbladet newspaper reported on May 7 that the agency had begun an investigation.)

a separate investigation by the ethics of Karolinska council of misconduct allegations Pierre Delaere, a surgeon at UZ Leuven, Belgium, Macchiarini had cleared of wrongdoing.

spokesman Claes keisu Karolinska Institute said the institute is working on an English translation of the report of Gerdin, which should be available next. Macchiarini week and others will then have two weeks to comment on the findings. Vice Chancellor of Karolinska will then decide what action to take, said keisu. He said a decision is expected in mid or the end of June

Mexico has one of type 2 diabetes rates in the highest world, with 12% the population suffering from the condition, compared with 9% of people in the United States. The Mexican government is so worried that he recently declared a state of emergency and introduced a tax on soda and junk food. But a new study shows that some Mexicans may be more at risk of developing diabetes, regardless of their state of health are diet. The reason may be their Mayan ancestry, which carries with it the genetic variations associated with the disease.

"This finding is important because it could provide clues on how to fight against the disease and to plan public health strategies," especially for people of Mayan language, said María Guadalupe García, geneticist at the autonomous University of Yucatán (UADY) in Mérida, who was not involved in the research.

There may be less Maya today at the height of culture 3000 years ago, but they never disappeared. Today, speaking Maya people constitute the second largest indigenous group in Mexico, with 800,000 people living mainly in the Yucatan peninsula in south-east. Isolated culturally and geographically from other ethnic groups for thousands of years, the gene pool Maya grew increasingly homogeneous. As tends to happen with an isolated population, genetic variations that are rare in other groups became common among the Maya. clinical biochemist Marta Menjívar of the National Autonomous University of Mexico (UNAM) in Mexico City asks whether any of these changes could increase the risk of Maya for diabetes, a growing problem in the southeast of Mexico.

team Menjívar surfed across the genomes of 575 people Maya looking for 10 genetic variants that had previously been linked to diabetes risk. They found that two are particularly common in the Maya, the researchers will report in the next month number Gene .

relatively homogeneous gene pool Maya made the changes easier to spot, says Julio César Lara Riegos, UADY geneticist and senior author of the study. But they probably are not restricted to the Mayan communities. Most Mexicans are mestizos, mixed with European, African, and Aboriginal ancestry. The average mestizo have Aboriginal ancestors about 55%, said Menjívar. This makes the study of the genetics of specific indigenous groups essential to the understanding of the risk factors that may be present in the larger Mexican population, said Xavier Soberon, director of the Mexican National Institute of Genomic Medicine (INMEGEN) who was not involved in the research.

It could also lead to personalized treatments for various Mexican ethnic groups and their mestizo families, said Ángeles Granados, a biochemist at the UNAM and a co-author of Gene paper [ElleétudiedéjàcommentleprofilgénétiqueuniquedelaMayapeutaccélérerletravaildecertainesenzymesconduisantàl'éliminationrapidedesmédicamentspourlediabètedeleurcorps"Celapourraitexpliqueraumoinsenpartiepourquoicertainsdiabétiquesnesontpasbienmédicamenteux"dit-elle

Understanding this process could help doctors know when to reduce or increase the doses of these drugs to their patients. It could also help Granados and other researchers to develop drugs that are resistant to breaking so quickly and, therefore, would be more effective for patients Maya, and for anyone else who shares this particular genetic variant.

But other scientists remain skeptical. "We can not start talking about improved treatments for Maya because diabetes is a complex disease involving many unknown risk factors, said Teresa Tusié Luna, a human geneticist who studies diabetes at the National Institute of health sciences and nutrition Salvador Zubiran in Mexico City. and all of these risk factors are genetic. Mexican genomes could not have changed in 20 years, but there are more cases of diabetes in the country today ' hui a few decades ago. This means that the modern lifestyle may have something to do with the increase, but Tusié Luna warns that we are just beginning to explore how both genetic and environmental components interact with each with others regarding diabetes.

Lorena Orozco, another human genetics at INMEGEN, concerned about the methodology used in the study. "It is difficult to associate the risk of diabetes because Maya that our sample sizes are still small, and that is an intrinsic problem of working with ethnic groups. " Does this mean that we should stop studying? "No," Orozco said, "we just have to be careful."

A highly anticipated trials of Ebola drug that has shown promise in monkeys was arrested soon after he apparently failed to show a benefit for patients.

the company that developed the drug, Tekmira Pharmaceuticals in Burnaby, Canada, and the Wellcome Trust, which sponsored the trial, announced today that they would not register because all other patients that the trial had reached "a predefined statistical parameter." initial results suggest that the addition of more patients in the study "was unlikely to demonstrate an overall therapeutic benefit to patients," said the Wellcome Trust in its declaration.

scientists have yet to analyze the data collected to learn more about how the drug, called TKM-Ebola Guinea, was tolerated and the specific effects it had on the disease outcomes said Peter Horby of the University of Oxford in the UK, who led the study. The trial, which began in March in Port Loko, Sierra Leone, which aims to enroll 100 patients. The company did not say how many patients have been enrolled to date.

The drug faces several obstacles in the trial, said Thomas Geisbert of the University of Texas Medical Branch in Galveston, who tested TKM-Ebola in monkeys and 'found the three protected animals that received from a normally lethal dose of Ebola virus. TKM-Ebola Guinea is a set of small RNA molecules packed into lipid nanoparticles. RNA interferes with three Ebola proteins and prevents the virus from replicating. Geisbert said that lipid nanoparticles used in the human trial are an older formulation than in recent monkey experiments. The previous version protected only about half of the monkeys in the previous tests, he said. "You compare apples to kumquats," he said. But the new formulation was not due to security phase I trials in humans and therefore could not be used in patients Ebola.

The trial design was also a challenge, said Geisbert. Many say that the allocation of patients to a placebo arm is unethical, so the TKM-Ebola trial was a single arm study supposedly in which everyone in a treatment center receives the drug and their survival compared with patients in centers not involved in the trial. But it makes the data very difficult to interpret, said Geisbert. "You can not draw reasonable conclusions. I doubt that something out that will tell one way or another" if the drug benefits patients. The end of the trial should not be the end of the drug, he said. "If you can not get an answer, and then you want to kill the drug? It's crazy."

The other drug considered the best shot in the fight against Ebola, cocktail 'zmapp antibody, is still being evaluated in a test. The National Institute of Allergy and Infectious Diseases (NIAID) launched the lawsuit in February in Liberia and the United States. It then spread to Sierra Leone and is about to enroll patients in Guinea as well, said Anthony Fauci, head of NIAID, located in Bethesda, Maryland.

The trial zmapp is a different trial design TKM-Ebola. He attributes randomly patients receive either three infusions zmapp and supportive care only or supportive care, including fluids and treatment of secondary infections intravenously. Fauci is optimistic that the trial zmapp give a clear answer. More than 30 patients have been enrolled, he said. "We are likely to need many more patients than to get a result, but less than 100." With Guinea added to the test, this should be accessible, he said.

* The Ebola virus files: science and science Translational Medicine made a collection of research and articles on Ebola virus and the current epidemic available for researchers and the general public.

If the World Health Organization (WHO) is to better protect humanity from the great epidemics, will change fundamentally. This is the conclusion of an independent committee to evaluate the treatment of Ebola outbreak in West Africa, which killed more than 11,000 people WHO. The report, released today, is very critical of some aspects of the response from WHO and makes recommendations for major reform of the structure and processes of the organization's decision-making, including the proposed create a new Center for Emergency Preparedness and response in WHO.

But the report also concludes that the WHO needs more power, more money and more support from Member States to fulfill its role. "I think this is an open and important report," said Preben Aavitsland epidemiologist epidemiological Kristiansand, Norway, which helped develop the International Health Regulations (IHR), a 05 treaty that defines what powers who in an international crisis health. "The authors are not afraid to make bold proposals."

Founded in 1948 as a United Nations agency, WHO is "the attainment of all peoples of the highest possible level of health." But there is broad agreement that botched its response to the Ebola outbreak last year. in March, a group of six independent members led by Dame Barbara Stocking, the former general director of Oxfam UK, was appointed to watch what went wrong and what should be changed. panelists questioned WHO sources and outside experts, met with representatives of many relief organizations, and flew to the affected countries in West Africa.

in the report, the defects of the WHO panel to several problems, most notably for "significant unjustified delays und" declaring the outbreak a public health emergency of international concern (PHEIC). WHO has not label the epidemic USPI formal recognition of the threat to global health, until August 8, more than 4 months after the outbreak was detected. By then, nearly 2,000 cases were reported.

The report acknowledges that the assessment of the situation at the beginning of the epidemic was complicated by several factors. Patients were hidden or being hidden by the family members, for example, and there was a collective denial about the scale of the epidemic in the affected countries. However, WHO should realize that the situation was out of control earlier, the report said.

"In the early stages of the Ebola crisis, the messages were sent by the experienced staff at headquarters and the Regional Office for Africa, even after deployment in the field, on the severity of the crisis. Either they did not reach senior executives or senior managers do not recognize their importance, "the panel wrote. Part of the problem was the WHO's organizational culture, which does not support "open and critical dialogue between senior management and staff or allowing risk-taking and critical approaches to decision making." The fears about the contest three African governments and the implications for trade and the economy kept the WHO to declare a PHEIC earlier, the authors ask.

instead of the current system, in which a home is a PHEIC or it is not, the report proposes to create "a new stage intermediate alert." But this would only complicate matters more, says Aavitsland. "I think it is better to lower the threshold for reporting of a PHEIC. The intention was never to make the threshold so high that it was regarded as a global crisis."

the report also concludes that, rather than establishing a new organization to address global health crises, WHO should be made "fit for purpose." to this end, it proposes to increase funding for the wHO 5% and to immediately establish a new wHO Centre for health and emergencies that could both fight against an epidemic and provide humanitarian aid, two tasks that are currently separated within the WHO. The center should be overseen by an independent board, write the authors, led by "a strong leader and strategic thinker with political, diplomatic, coordination of crisis, organization and management skills."

the new center is the most far-reaching proposal, said Aavitsland who think it is a good idea. But it can not go down well with the leadership of wHO, he adds, because it would effectively to create a state within a state.

increased funding is also unlikely to materialize, says John-Arne Röttingen, responsible for the control of infectious diseases at the public health Institute in Oslo Norway there. just a few weeks, the World Health Assembly (WHA), plans to raise the "contributions" were fresh-member countries -mainly rejection, he notes. "We just tested the appetite of Member States to invest, so I had hoped [the panel] would come with stronger language, "says Röttingen. (The panel wrote that it was "extremely disappointed" by the decision WHA and "requests the Member States to reconsider this decision" at the next meeting.)

The report criticizes WHO to take too time to coordinate the response to the epidemic and for not mobilizing community leaders, particularly women, from the beginning. It took too long to prioritize culturally appropriate messages to ensure support of affected populations, the report said.

the authors reserve a portion of their language most damning to the way WHO handled the communications, however.. "the Panel is clear that the WHO has failed to engage proactively with senior media and was unable to get command over the epidemic narrative This weakness has had repercussions in many areas of the response; better communication approach could improve confidence in WHO and reduced levels of fear and panic. "

the report has positive words for the WHO as well. Some were afraid that the role of the agency in the research and development of therapies and vaccines for Ebola could divert the fight against virus field. instead, "WHO should be commended for this work, as he stepped up to fill a void at a critical stage of the epidemic," the authors write. "the WHO should be involved in research and development for future emergencies. "Yet Röttingen said he had hoped for more concrete proposals and a statement of the responsibilities of countries to support research and development for neglected diseases.

the report also takes aim at the United Nations. Although the leadership of the United Nations was needed to galvanize a response, the United Nations Mission for emergency interventions resulting from Ebola (UNMEER) has not was very successful, they write. "What you do not need is a new UN mission being created in the middle of the crisis," Stocking said at a press conference Tuesday. during the Ebola outbreak, a coordination center set up by several countries in the Guinean capital, Conakry, has been closed, after which it took months for a new UN center in Ghana to go , she says. "It really does not make sense," said Stocking.

members of WHO states get their share of criticism as well. For example, over 40 countries have taken measures that interfered with traffic such as international tests Ebola quarantines or required-that are not recommended by WHO, a clear violation of IHR. "Accordingly, the affected countries faced not only political consequences, serious economic and social, but also the obstacles to receive the necessary staff and supplies."

To avoid such excessive reactions in the future, the authors propose to establish mechanisms that allow WHO to punish the country for inappropriate care. They also want to give countries an incentive to notify WHO health possible threats as opposed to deny or minimize their importance, eg by an insurance plan that allows countries to access emergency funds after WHO risk assessment.

The fundamental problem is that member states have been reluctant to truly embrace the meaning of the IHR, said Aavitsland. "In fact, they give up some power of their status at the WHO, the world community, when an international public health emergency is declared. But they are not willing to do it," he said. The only WHO currently has recourse against countries that do not play the rules is naming and shaming them and that does not work well, he said.

In fact, a 2011 review of the IHR, which Aavitsland helped produce, has some of the same points. But this report was never acted upon. "It was simply recognized and recommendations were not really discussed in detail," says Aavitsland. It was a mistake with far-reaching consequences, the new report notes. Had the recommendations been implemented, "the international community would have been in a much better position to deal with the Ebola crisis, "the authors write. They expressed their hope that this time action follow words. "The world simply can not afford another period of inactivity until the next health crisis."

This is the greatest danger, said Michael Osterholm, director of the Center for Research on Infectious Diseases and politics at the University of Minnesota, Twin Cities. "The good news is that this is a report that we can pass to the next level. But that means little unless it is translated into action." The next 30 to 60 days will show the actual weight of the report, he predicted.

Stocking acknowledged that getting the report implemented will be a tough act. "The more public pressure we get on this, the better," she said at the press conference today.

In a first response, WHO welcomed the report and noted that a committee to review the RSI will be convened by Margaret Chan Director General. there, "Member States can discuss the group's recommendations, including the idea of ​​establishing an intermediate level of alert for an alarm earlier than a full public health emergency of international interest, "the WHO said in a statement sent to reporters

* update, 7 July 13:15 .. This story has been expanded from its original version to include quotes from Rottingen, Stocking and Osterholm

Notch another victory for synthetic biology. Researchers report today that they have designed a common laboratory plant to produce the starting material for a powerful chemotherapy drug initially harvested from a Himalayan plant endangered. The new work could provide an abundant supply of the anticancer drug and make it easier for chemists to twist the compound to come up with safer and more efficient versions.

Throughout history, people have relied on plants for medicines. Even modern drug companies get about half of their new drugs from plants. But it is harder to do when the plants are slow growing and disappearing, like the Himalayan mayapple ( Podophyllum hexandrum ). The plant short leaves was the original source of podophyllotoxin, a cytotoxic compound that is the starting point of an anticancer drug called etoposide. The drug has been on the US market since 1983 and is used to treat dozens of different cancers, lymphoma lung cancer. Today, podophyllotoxin is mainly harvested from the more common American mayapple. But this plant is slow growing, that producing only small amounts of the compound.

Mayapples churn podophyllotoxine to defend against would-be munchers. To do this, plants use a step by step approach to synthesize their chemical defense. But because the synthetic pathway of the compound has not been developed, it was not clear which genes were involved in the seam of the molecule. What the researchers knew was that podophyllotoxin is not always present in the plant. "It is only when the sheet is hurt that the molecule is made," said Elizabeth Sattely, a chemical engineer at Stanford University in Palo Alto, California, who led the current research effort.

Sattely and his graduate student Warren Lau held that the podophyllotoxin-building proteins themselves were probably not made by the plant in response to injury. Thus, the pair made tiny holes in the leaves of the Himalayas healthy mayapples provided to them by a commercial nursery, to test the before and after to see what new proteins appeared around the damaged tissue. they found 31, which they classified probable function.

the couple then shrunk likely candidates for the enzymes in the production of podophyllotoxin focusing on the members of four classes known to carry out the right types of chemical reactions. They then spliced ​​genes for each of these enzymes in bacteria known to infect Nicotiana benthamiana , a fast growing Parent tobacco used as a sort of plant biologists laboratory rat. Bacteria easily infect tobacco and insert their genes into the plant tissue. Sattely Lau and inserted many combinations of genes for the enzymes they thought they could produce the desired compound. As they report online today in Science , they finally hit on a group of 10 enzymes that allowed the plant to make a molecule called (-) - 4'-desmethyl epipodophyllotoxin, a direct precursor to etoposide and a powerful anticancer drug in its own right.

"It is a great piece of work," said Sarah O'Connor, a biological chemist at the John Innes Center, a research institute on plants in Norwich, UK Finally, new job can give pharmaceutical companies a stable, abundant supply of their drug fight against cancer, and it can result in similar compounds that might work even better.

in a widely expected move, the World Health Organization (WHO) today approved antiretroviral (ARV) treatment for 37 million people infected with HIV worldwide. previous guidelines called for only treat the estimated 28 million people infected with HIV who have fewer than 500 CD4 cells per microlitre of blood. (The normal range is 0 to 10.) The new guidelines also call for providing the drugs to prevent pre-exposure prophylaxis to infection called HIV, or PrEP to all persons to "substantial risk" infection.

Currently, only 15 million people infected with HIV received antiretrovirals. But in rich countries, it is becoming increasingly common to start early treatment before the CD4 cells from a patient had significant declines. Large studies have shown that early treatment benefits for people infected with HIV and, separately, that ARVs significantly reduce the risk of transmission. Several similar PrEP studies have shown that ARVs protect uninfected people regardless of the transmission path.

The Joint United Nations Programme on HIV / AIDS previously called for "fast-track" approach to end the World AIDS epidemic in 2030 that would increase investments now needed annually to $ 21.7 billion by $ 12 billion . Accelerated target only call 81% of people infected with HIV to be on ARVs by 2020. There remains a huge question mark if the world is going to pay for these ambitious goals. This will require more domestic spending by low-income countries which are hardest hit by the epidemic, and the great contributions of rich countries.

WHO called the new recommendations of a "release early guidelines" and plans to release more comprehensive revisions in 2016. WHO has begun to publish HIV treatment guidelines in 02, how ARVs are recommended only for people who had less than 0 CD4.

When the plague swept Europe in 1665, no one could understand how the spread of the devastating disease. But after a tailor in the village of Eyam in the center of England died that September, people end up putting the two together. He had received a parcel fabric infested with fleas just four days before dying of bubonic plague. Within a month, five other villagers had died, and the local vicar convinced the city to voluntarily put in quarantine. It eventually became clear that he was smart, probably on rats that spread the plague so far and so fast.

But now it seems that the plague has not always infect fleas and disease may not have always spread so quickly and been so devastating. A new study of ancient DNA of teeth 101 skeletons Bronze Age found that seven people living there from 2800 to 5000 years in Europe and Asia have been infected Yersinia pestis , the bacterium that because the plague. But their strains of Y. pestis were missing a gene that allowed it to infect fleas, according to the study published today in Cell . This pushes the first evidence of plague nearly 3,300 years and offers a key indicator of how this disease has become so contagious. "It's really cool that they can locate the acquisition of key genes that enable the movement of this bacterium in fleas," says evolutionary geneticist Hendrik Poinar of McMaster University in Hamilton, Canada, who was not involved in the study.

plague caused the death and destruction in Europe at least since Roman times, the launch of three major pandemics that changed the course of history it plague of Justinian 541-544, which weakened the Byzantine Empire, the black Death, which killed nearly half the population of Europe between 1347 and 1351, and the Great plague of 1665, which lasted more 30. the ancient DNA researchers have shown in recent years that Y. pestis caused these three pandemics. But so far they have been unable to determine whether Y. pestis caused reported scourges there 2224 years in China and there are nearly 2500 years in Greece. they suspected that older versions of the plague are not as fast devastating spread, but they could not test this idea because they lacked samples earlier pathogens.

Now, an international team of researchers and archaeologists ancient DNA has solved the mystery almost by accident after sequencing the genomes of 101 skeletons from the Bronze Age in Europe and Asia. The team began by trying to identify the origins and early European migration. DNA samples have revealed that a group of pastoralists, the Yamnaya, swept Europe in the plains of Russia and Ukraine today somewhere between there 5000 and 4800 years, bringing their culture and, perhaps, the proto-Indo-European language with them. But the archaeologist Kristian Kristiansen from the University of Gothenburg in Sweden wondered if they also brought disease and suggested that researchers are testing the human DNA Bronze Age in Europe and Asia to the know.

The team, led by evolutionary biologist Eske Willerslev of the University of Copenhagen, screened 89 billion short DNA segments of teeth 101 people. Raw data included bacterial DNA in the teeth, generally considered "data on legacy waste," says Willerslev because it can contaminate human DNA samples. They detected Y. pestis people seven, ranging from the Bronze Age skeletons dating from 4800 years ago in Russia, Estonia and Poland, to an individual who lived Iron Age there are almost 3,000 years Armenia.

When they sequenced the complete genomes of Y. pestis DNA in these seven people, the team found that the bacterial genomes from the first samples lacked two genes that helped Y. pestis escape the immune systems of humans and chips during the black Death. In particular, the Y. pestis in the early Bronze Age individuals lacked a gene called Yersinia murine toxin , which protects the bacteria toxin in the gut fleas. So although these people the Bronze Age have suffered from the plague, they probably obtained from airborne droplets, contaminated food, or the transmission of bodily fluids rather than fleas that infested rodents, such as have done Europeans during the black Death and other pandemics.

using the same samples, the team also traced the evolution of Y. pestis and confirmed that it has evolved from a soil bacterium closely related to Yersinia pseudotuberculosis, a bacterium that causes scarletlike Far east fever in humans and is most often spread through food. Both bacterial lineages diverged there are about 55,000 years old. This date has large margins of error, but suggests that Y. pestis is much older than the estimates of thought-earlier suggested it originated there are only 3300 years. But researchers now realize that this was probably not before the end of the Bronze Age that bacteria have evolved from a less virulent species that have spread more like flu, tuberculosis or AIDS that bubonic plague, which is transmitted by flea bites on the skin.

"This suggests that it is a disease quite different in the Bronze Age than it was in medieval times," says Johannes Krause, a paleogeneticist the Institute Max Planck for science in human history in Jena, Germany, who was not involved in the study. Poinar agrees that the most exciting part of the paper is that it solves a longstanding mystery about how that bubonic plague was able to spread so rapidly in the Middle Ages He said:. ". The entire ecology flea rodent plague is what has led to major pandemics of bubonic form of the plague in Europe "

The plague was devastating the age of bronze too. the researchers believe that if the invading armies of the Russian steppe has the plague with them in Europe, although it is not spread by fleas it would have wiped out small bands of European farmers and made them vulnerable territory the invasion, much as the Spanish conquistadors infected Indians with smallpox. And the plague was just an arsenal of devastating diseases that have shaped the course of human history. "the most important message is we now can do it for all kinds of diseases, "said Willerslev.

inhibitors Checkpoint, designed to unleash the power of the immune system on tumors are some of the most impressive new treatments against cancer. But most patients who receive no benefit. Two new mouse studies suggest a surprising reason why these people may not have the right mix of bacteria in their guts. Both studies show that the composition of the gut microbiome-the living microorganisms swarms naturally in the intestines determines the effectiveness of cancer immunotherapies are.

The studies are the first to connect our intestinal inhabitants the power of checkpoint inhibitors, drugs which counteract one of the tricks of survival of cancer. To curb the attacks on our own tissues, immune cells carry receptors that connect to their business. However, tumor cells can also stimulate these receptors, preventing the immune system from attacking them. Checkpoint inhibitors as ipilimumab, which has been on the market since 2011-nivolumab pembrolizumab and prevent tumor cells to stimulate the receptors.

The new work could change the way doctors use drugs. "The two papers convincingly show that microbes can affect treatment," says immunologist Yasmine Belkaid of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, who was not connected to the new studies. In past, researchers have generally sought mutations in the genomes of patients that could explain why a particular checkpoint inhibitor does not work, says molecular biologist Scott Bultmann of the University of North Carolina School of Medicine in Chapel Hill. the new results are encouraging, he says, because "it is easier to change your intestinal microbiota of your genome."

Checkpoint inhibitors may shrink tumors and extend patients' lives, sometimes by years. Yet only a fraction of the beneficiaries to improve. Approximately 20% of melanoma patients treated with ipilimumab live longer, for example. Researchers do not know what distinguishes them from the other 80%.

A side effect oncoimmunologist Laurence Zitvogel direction of drug Cancer Campus Gustave Roussy in Villejuif, France, and colleagues to the microbiome. The ipilimumab often triggers colitis, an inflammation of the large intestine, where some of our microbiome lives. This side effect suggests checkpoint inhibitors and interaction between the microbiome. Following this possibility, the researchers tracked the growth of tumors implanted in mice without intestinal bacteria. Inhibitory control point, they tested was less powerful animals.

Further analysis by Zitvogel and colleagues suggested that some bacteria in Bacteroides and Burkholderia genres were responsible for the antitumor effect of the microbiome. To confirm this possibility, the researchers transferred the microbes in mice that lacked the intestinal bacteria or feeding animals microorganisms or by giving them Bacteroides rich excrement of certain treaties ipilimumab patients. In either case, an influx of microbes reinforced the response of animals to a checkpoint inhibitor. "Our immune system can be mobilized by the trillions of bacteria in our gut," says Zitvogel.

immunologist Thomas Gajewski of the University of Chicago (UC) in Illinois and colleagues came to the same conclusion after noticing a disparity between the mice they had obtained from two suppliers. melanoma tumors grew more slowly in laboratory mice that Jackson mice Taconic Farms. the microbiomes rodents tend companions cage-homogenize the animals eat feces to the other, the researchers housed mice of both suppliers together. Cohabitation erased the difference in tumor growth, indicating that it depends on the types of microbes in the guts of rodents .

When they analyzed the microbiomes mice, researchers have identified a bacterial genus known Bifidobacterium . The team found that feeding mice from Taconic Farms a probiotic that contains several Bifidobacterium species have increased the effectiveness of a checkpoint inhibitor against tumors. "The endogenous antitumor response is greatly influenced by your commensal bacteria," says co-author Ayelet Sivan, who was a Ph.D. student at UC when the research was conducted. Both groups reported their findings online today in Science .

The two teams involved different bacterial groups, but that does not worry microimmunologist Christian Jobin of Florida College of Medicine University Gainesville. "Different medications, different bugs, but the same criteria," he said. He added that the new work complements a pair of 2013 studies which demonstrated that the microbiome affects how chemotherapy works.

The discovery "opens up new ways to potentially increase the therapy," says Cynthia Sears, an infectious disease specialist at Johns Hopkins School of Medicine in Baltimore, Maryland. For example, it may be possible enhance the antitumor response of a patient with probiotics. But researchers also see potential obstacles. as noted Zitvogel, regulators in the US and Europe have not approved the use of probiotics for patients cancerous. Also clear is how microbes stimulate immune response-intestinal bacteria are essential for the development of the immune system, but researchers are not sure how they twist its function in adult animals. And scientists are learning how to tinker with the microbiome. "clearly we can meaningfully manipulate the microbiota and create positive health effects," says Sears. However, the researchers say, studies suggest that we can have new powerful allies in the fight against cancer.

The war against malaria has a new ally: a controversial technology for the dissemination of genes in a population of animals. Researchers now report that they have used a so-called gene reader to effectively confer mosquitoes with genes that should make the parasite shed malaria and unable to spread. On its own, gene reader will not get rid of malaria, but if it is successfully applied in the nature of the method could help eradicate the disease, at least in some corners of the world.

The approach "may lead us to zero [cases]," says Nora Besansky, a geneticist at the University of Notre Dame in South Bend, Indiana, who specializes in mosquitoes carry malaria. "mosquitoes do their own work [and] reach places that we can not afford to go or to go to."

But test this promise in the field may have to wait until a broader debate on the readers gene is resolved. the essence of this long-discussed strategy for the dissemination of a genetic trait, such as disease resistance, is to bias the heritage so that more than half the expected subsequent generation inherits. gene drive concept has attracted new attention earlier this year when geneticists studying fruit flies adapted a gene editing technology called CRISPR-case.9 to help spread a mutation and were surprised to find it worked so well that the mutation has reached almost all offspring fly. Their report, published this spring Science came out less than a year after eLife paper discussed the feasibility of CRISPR-case.9 gene drive system, but warned that it could disrupt ecosystems and wipe populations of entire species.

A firestorm quickly erupted on the risks of experimenting with genes players, applying them in the field Nevermind. The US National Academy of Sciences (NAS) convened a committee to assess risks and propose protection measures, and the authors of eLife and Science documents have laid lines guidelines for experiments.

Meanwhile, over the past 20 years, Anthony James, a geneticist at the University of California (UC), Irvine, dreamed of engineering a gene unit that would spread makes DNA mosquitoes unable to host the malaria parasite. In 2012, his team stuck mouse genes for antibodies that make rodents immunized against the agent of human malaria and put them in a species of mosquito that spreads malaria in India. Antibodies, as expected, interrupted the parasite's life cycle in the insect. But James was no way to push the antibody genes in millions of mosquitoes in nature. It explores the development of a training method of genes using transposable elements, odd bits of DNA that can jump between chromosomes, but never succeeded.

Earlier this year, however, James received an email from Ethan Bier, a geneticist at UC San Diego whose lab has done research soon-to-be-released genes drive in flies fruits. Bier thought he had a solution to the dilemma of James. "As soon as we saw [gene drive] might work, we thought of mosquitoes," says Bier. James was delighted. "I looked and realized their data [they] is what I was proposing obsolete."

But he wonders if the Bier gene drive system could carry heavy 17,000 DNA bases containing the genes mouse antibody. "the question was" would it carry a large cargo will remain active? "James remembers. he and Bier teamed to see.

Valentino Gantz laboratory Bier and Nijole Jasinskiene , a molecular biologist at UC Irvine, began with male and female engineering Anopheles stephensi to execute the gene drive system. They designed the system so that, along with the dissemination of antibody genes from one half of a pair of chromosomes to the other, the polarizing key inheritance- it would also cut a piece of a gene for eye color When coupled with the modified mosquitoes normal, they could quickly see if the gene player had wrought .. offspring who also inherited the antibody genes had white eyes

technology was effective, giving about 99% of the offspring of the male transgenic with added genes, teams of Bier and James reported today in the Proceedings of the national Academy of sciences . And, as expected, these genes were active in mosquitoes. Previous experiments had shown that if the antibody genes were expressed, they thwarted the parasite. And modeling suggests that a gene reader of this effectiveness, it should only take about 10 generations of mosquitoes for malaria genes to completely infiltrate a population.

The system was not perfect. The gene reader does not work as well when started in female transgenic mosquitoes. In addition, the case.9 protein used in gene editing technology can be toxic to mosquitoes, the team had to twist where insects it was made and how to improve the survival rate of offspring. Yet the strategy is working. "It is really a big problem," says Besanksy. "It is not only a gene drive system. It is a gene drive system that carries suppressors genes." "We have all the pieces," adds James. "It is a matter of [making] a product that people want."

, which is the big event. James, Bier, and colleagues adequately addressed concerns about accidental releases GM mosquitoes, say several external researchers contacted by science . insectariums were behind five sets of doors, and they used a mosquito does not survive in California, should he manage to escape.

But before the work continues, says evolutionary engineer Kevin Esvelt Harvard University biologists should look at the ecological effects of changes induced genes, make sure that the changes are stable for many generations, and develop a way to counter or get rid of gene drive in case of problems.

Because pest control genes should continue to propagate indefinitely in a population of mosquitoes, national and international regulations must be developed before the genes drives are deployed in the field, says sociologist Kenneth Oye the Massachusetts Institute of Technology in Cambridge. The drive ratio of the NAS gene, due next year, can help in this regard. "How will we decide as a society whether, when and how to use gene reader to solve a problem?" Request Oye.

Esvelt, which is already in discussion with the public, physicians and government officials about the spread of genes of Lyme disease in anti-mouse even if the genes drives has not been shown in mammals, said a consensus must be reached. "at the end of the day, unless you have broad public support, you can not do it. "

James accepts that his dream may be deferred for now." if it is that we are too far ahead of the curve, we will just wait for people to catch, "he said. "I hope not to have to wait for the rest of my productive career, but if we can not find a way to do it ethically, it will not."

Seven months after South Korea has identified its first case of Middle East Respiratory Syndrome (MERS), the country called the epidemic officially over soon midnight that night. The last patient infected with MERS virus died November 25 - no MERS but of malignant lymphoma which had also prevented to eliminate the virus. Strictly following the guidelines of the World Health Organization, the Korean authorities waited 28 days - two times longer than the incubation period of 14 days for the virus MERS - to declare the formal end of the epidemic.

the last patient, a man of 35, was already suffering from lymphoma when he was in contact with a patient MERS May 27 Getting sick on June 6, he was hospitalized at Samsung Medical Center and confirmed positive for MERS June 7 He was then transferred to the hospital of Seoul National University where he continued to show signs of the virus until successive tests on 30 September and 1 October were negative. On 2 October the Ministry of Health press release noted that 116 days was the longest a patient has never confirmed MERS remained positive. "His condition underlying immunocompromised kept his body to get rid of the virus," the ministry said.

The patient returned to the hospital with a fever on October 11 and tested again positive for MERS virus. experts from the Korea centers for disease Control and Prevention (KCDC) concluded that a certain minimum amount of genetic material of the virus (MERS is the disease) had remained dormant in the body of the patient, according to a Ministry of health press releases. despite believe that there was little risk of transmission, KCDC made 61 contacts the patient under home quarantine.

during hospitalization, the man alternately tested positive and negative for the virus. meanwhile, the lymphoma progressed and caused his death on November 25.

epidemic MERS South Korea came from a Korean man single that brought home virus after a trip to the Middle East. He sought treatment for fever and before MERS was diagnosed on 20 May, the virus had spread among health care workers and patients in several different hospitals. The epidemic has caught the South Korean health sector by surprise. The hospitals have been slow to identify and isolate those infected. And health authorities have stumbled in their initial efforts to find contacts and to enforce quarantines. But optionally worked controls. There was no new confirmed infections after July 4th. Prime Minister Korean Hwang Kyo-ahn said a "de facto end" to the epidemic, July 28. But by then it had become by far the largest outbreak outside the Middle East with 186 confirmed infections laboratory and 36 deaths.

Some children can handle scarf peanuts, but only one nut can kill others. A new study suggests one reason why children develop life-threatening food allergies. At birth, their blood is rich with cells that can promote a hyperactive immune response.

Previous studies of some of the approximately 6 million young Americans who develop food allergies suggest that abnormalities begin to brew earlier. By sampling the baby's blood from the umbilical cord, researchers can get a quick overview of the immune system of the child. They found that the blood of children who later develop food allergies contains more chemical signals that promote inflammation, and lower than normal concentrations of natural regulatory T cells, the immune system responses low tone.

To understand what changes could be key to the development of allergy, Zhang Yuxia immunologist of the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia, and colleagues recruited over 1,000 new -nés. The researchers analyzed the immune cells in blood samples from the umbilical cord of children. Then when the children were aged 1 year, the team tested whether they were allergic to a range of foods, including eggs, cow's milk, and peanuts.

The young children who had food allergies also showed a higher number of a type of white blood cells called monocytes at birth. Monocytes form the reserves of the immune system. When we get sick, they turn into cells such as macrophages that fight pathogens. Zhang and his colleagues found that children prone allergies monocytes are not only more numerous, they were also hyperactive, react more vigorously to bacterial molecule that makes monocytes children with allergies. In other words, they responded more aggressively to apparent threats made monocytes in toddlers who develop allergies.

Previous studies have not linked hyperactive monocytes food allergies in childhood, the researchers tested the cells' effects on other immune cells. In culture dishes, the signals emitted by monocytes of allergic children caused natural regulatory T cells that normally suppress allergic reactions to the contrary; they turned into T helper cells that drive these reactions. monocytes molecular messages also stimulate the "undecided" T helper cells to convert into T helper cells allergy-promotion, the researchers report online today in Science Translational Medicine .

What do these results, Zhang suggests, is that the immune system of some children "at birth has already begun" to develop allergies. Why allergy-prone children are born with hyperactive monocytes is not clear, said Zhang. A mother may be exposed to something during pregnancy, perhaps in his food, which changes the developing immune system of children. Genetic differences could also influence the sensitivity of monocytes.

"There is a mechanism highlighting somewhat different from that which has been shown before," said immunologist Oliver Burton Children's Hospital Boston, who was not connected to the 'study. But the large number of children in the study and careful analysis the authors make credible results, he said.

"The document provides laboratory tests to show that infants who develop food allergies may be different from newborns who don 't," says allergist and clinical immunologist Marshall Plaut of the Institute National allergy and infectious diseases in Bethesda, Maryland. He cautions, however, that researchers have yet to confirm that monocytes in the release of the body the same chemical signals than those released by the monocytes in the laboratory.

Because the chemical signals released by hyperactive monocytes promote inflammation, the study implies that the suppression of inflammation may curb allergies. Scientists suggest that we need more research on the measures, such as changing the food system of the mother, which could reduce inflammation.

Babies born vaginally are expected to have an advantage over those born by Caesarean section. They pick up bacteria from the birth canal of the mother, which scientists believe helps protect against asthma, obesity, and other health problems as they age. Now, a new study offers advice that researchers may be able to provide these same benefits for babies by C-section "redo" their microscopic community shortly after birth.

Although the work is very preliminary, it is also "a very interesting and simple procedure" which opens new avenues of exploration, said Dennis Kasper, a microbiologist and immunologist at Harvard Medical School in Boston, who was not involved in the study.

mothers in labor, like the rest of us, boast of a constellation of bacteria anywhere in their body is called the microbiome. Babies born vaginally develop a microbial community that looks at first that the vagina of their mother, while babies enter the world via C-section have a similar microbial makeup to the skin of their mother. These differences, in turn, have been associated with an increased risk of asthma, allergies, obesity, and immune deficiencies, in human studies and mouse. Exactly how many mounts risk is unclear, but studies have attracted the attention of many scientists.

This is the next step "if logic" according to Maria Gloria Dominguez-Bello, a microbial ecologist at New York University School of Medicine in New York: whether the microbiome of a baby born by caesarean section could be moved immediately after birth. Dominguez-Bello was particularly eager to test it because, after 11 years working in Puerto Rico, she was alarmed by the extraordinarily high levels of C-section here, almost 50%, and in other countries of America Latin. "There's this idea that C-section is fine and there is no need to go through the work," she said, and many cesarean sections are not medically necessary.

Then Dominguez-Bello teamed up with computational biologist and expert microbiome Jose Clemente C. Icahn School of Medicine New York City's Mount Sinai to launch an unusual clinical trial. They and their colleagues recruited mothers programmed to have a caesarean section. An hour before the operation, the researchers placed a sterile gauze in the vagina of the mother, where he was left until just before surgery. At that time, the team placed in a sterile container. Within 3 minutes of great baby's entrance, whipped doctors gauze and rubbed all over the body of the newborn, starting with the lips and face

"We know this is an approximation. We can not reproduce all the factors that are involved in the work, "says Clemente, noting that his own daughter was in the birth canal" for hours. "At most, infants in this study were rub-down one minute with bacteria from their mother's vagina.

However, the treatment seems to have an effect. Repeated sampling of bacteria on the skin, in the anus and in the mouth over the next 30 days revealed a change to a typical vaginal microbiome. This was particularly true of areas on the skin and mouth. in particular, the researchers report today in Nature Medicine , there was "early enrichment" of Lactobacillus bacteria, followed within a week by 2 Bacteroides -two types of healthy bacteria that are significantly decreased in babies born by caesarean section. "If you expose a baby [the] vaginal secretions of her mother, pick up bacteria in different locations and flowers," said Dominguez-Bello.

But even the authors acknowledge some large reserves. The number of babies in this pilot study was very small: Just four received treatment gauze, while seven others born by Caesarean section did not. (There was also a comparison group of seven babies born vaginally.) Because there is a significant variation in the microbiome in C-section and vaginal birth group, a small sample size, it is particularly difficult to catch lasting changes in the microbiome. And there was less difference in the anal microbes in four babies treated than on other sites, compared with those born by Caesarean section are not treated. This suggests the intestine may have been less affected than other parts of the body by the experience of gauze, because the bacteria are ingested by the baby, as they can be during a vaginal birth. Finally and critically, there is no way of knowing if the microbiome changes will affect health on the road.

Dominguez-Bello and Clemente recruited 86 families to expand the approach, and are hoping to add many others and follow the baby for at least a year.

Although it is not known if this strategy will affect health later, and indeed, the link between C-section and health effects is still just a hypothesis -the approach so easy it's tempting to try. Indeed, one of the authors of the article, the biologist Rob Knight computing at the University of California, San Diego, he applied to his daughter when she was born by emergency Caesarean section last few years, before the start of the study. "We took things in hand," he said in a TED talk in 2014, "and made sure that she was born with germs, she would have naturally."

* Visit our topic page microbiome for related information.

Children in Africa and parts of Asia are victims of toxins "invisible" in the epidemic-fungal foods that can retard growth and delay their development, according to a new report by the international Agency for cancer research and funded in part by the Bill & Melinda Gates Foundation. The two main toxins-aflatoxin and fumonisin-are present in dangerously high levels in peanuts, cassava and corn, which constitute the bulk of the Benin child feeding in Kenya.

The toxins have long been known to cause liver cancer and, in high enough concentrations, death. But this is the first time they have been shown by many studies to contribute significantly to growth retardation in children.

"There is a huge problem" largely unknown in developed countries, said J. David Miller, a fungal toxicologist at Carleton University in Ottawa and one of the authors of the report. "Huge amounts of money are spent [in the United States and Western Europe] to prevent you from being exposed to these types of toxins."

The toxins, byproducts of Aspergillus and Fusarium fungi are endemic in corn fields worldwide. The difference is that US and European producers are doing everything possible to remove contaminants to meet strict standards for human consumption, 20 parts per billion (ppb) in the United States and only 2 ppb in Europe. The fields are highly processed, and crops are treated so that any remaining toxins are leached. Foods that do not conform to standards used as animal feed or burned. In total, American food producers spend between $ 500 million and annual management of fungal toxins than $ 1.5 billion.

But in countries where food shortages are chronic, some farmers have the ability to process their crops and enforcement is lax. Premium products are sold for export. "It makes me cry when I'm in Nampula, Mozambique, and women are there on the floor, sorting grain by hand, trying to get the best whole grain and then send to Europe" said Peter J. Cotty, a plant pathologist with the US Department of agriculture agricultural Research Service in Tucson, Arizona. "And he gets rejected by Europe. But there are in the European market for bird feed, which allows 50 [ppb] that person in a developed country would never allow people to eat. "

People back home are stuck with food at even higher levels of toxicity sometimes in the thousands of ppb.

researchers are not sure exactly how toxins affect children, but the new report brings together six recent studies that show that children with high levels of biomarkers of the toxin in the blood are shorter and weigh less than other children their age. They also grow at a slower rate than their peers. Preliminary studies suggest the effects may have something to do with the activation of the immune system and how the body absorbs nutrients.

The report also makes recommendations to control the problem, including the treatment of fields with natural biocontrol, improving food storage conditions and the diversification of supply. It also calls for the development of rapid screening methods that would be able to quickly detect toxins in the blood.

Miller said the problem is as much social scientist. "It just seems to be intractable for a variety of reasons," he said. "If you look in the literature, it was 50 years ago, people in public policy said more or less exactly what we say now. And here we are."

A small crowd of villagers waiting in a concrete school building low Pedda Srirampuram, a village in the southern Indian state of Andhra Pradesh. The morning air is crisp and the men and women dressed in light shawls and sweaters. Each holds two bags with a plastic medical records, the other with a transparent plastic container of urine. They are lining up to be seen by one of the four young men with two large wooden tables.

A researcher named Srinivas Rao is sitting at the first table. "What is your name?" He asks, a short stiff man who is next in line. "RE. Kesava Rao," the man replies, put his medical records. Rao, the researcher, leafs through the pages, noting details. "His kidneys are not working at all," notes Rao. "Both his kidneys."

This is a disease that has a significant mortality. People who [otherwise] work, raise a family are dying. It is quite extraordinary.

Kesava Rao, 45, has chronic kidney disease of unknown etiology (CKDU) and depends on dialysis to survive. "Every week, I undergo dialysis, 4 weeks a month," says Rao. a man with a soft voice with a ready smile, Rao worked all his life on construction sites or in coconut farms. he lived a healthy life and almost never seen a doctor, he said, until the fever has led to an examination and diagnosis Rao. did not have diabetes or until her kidneys failed, hypertension, the two leading causes of chronic kidney disease in the world. No more than most other villagers who gathered here, all patients with chronic kidney disease, waiting to get a free blood test for creatinine, a metabolite and a proxy for kidney function, and give samples of urine and blood for research.

The Andhra Pradesh coastal region is at the heart of what doctors and local media called a CKDU epidemic. There is little data on the prevalence rigorous, but unpublished studies by Gangadhar Taduri, nephrologist at the Nizam Institute of Medical Sciences in Hyderabad, in the neighboring state of Telangana, suggest the disease affects 15% to 18% of the population in this agricultural region, known for rice, cashew and coconut. Unlike the most common type of CKD, especially seen in the elderly in urban areas, CKDU seems a rural disease, affecting agricultural workers, the men of the majority of them between their 30 and 50. "It is a problem of the poor, "said Taduri, who leads the team of researchers in the village.

a rash of similar outbreaks in other countries stressed that it is a global problem. Some rice-growing areas of Sri Lanka have their own epidemic and endemic in the producing areas of sugar from Mexico and Central America (Science, 11 April 2014 , p. 143). It has also been reported in Egypt. Everywhere, prevalence figures are scarce and uncertain, but "there is a lot of concern," said Virginia Weaver, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health University in Baltimore, Maryland. "This is a disease that has a significant mortality. People who [otherwise] work, raise a family, are dying. It is quite extraordinary."

experts and public health researchers are alarmed and confused. In Central America, which was the most affected, the main hypothesis is that this is an occupational disease caused by chronic exposure to heat and dehydration in the cane fields. Here, in Andhra Pradesh, Taduri and his colleagues believe that natural toxins in lithium drinking water, for example, could help. Using samples of blood and urine of Pedda Srirampuram, "we will evaluate if [trace elements] are really present in the body or not," says C. Prabhakar Reddy, one of the researchers who collect the samples.

But in India, Sri Lanka and Central America, researchers attempt to explain CKDU pursue a wide range of ideas, including the excessive use of over the counter pain medication and exposure to pesticides . Nephrologist Ajay Singh of Harvard Medical School in Boston found high levels of silica, found in some pesticides in drinking water in the region, and thinks he could be responsible. "There is a smoking gun" he says, but he concedes.. "I do not know if smoking gun is responsible"

As global disease becomes clear, the search for answers is accelerating beginnings an international scientific network to study CKDU take shape, and researchers are working on a simple and accurate diagnosis so they can map the incidence in the world and try to correlate with possible causes.

Like most places CKDU is endemic, India does not have a good idea how many people have the disease (also known as CKDnT for nontraditional causes). But anecdotal evidence from Andhra Pradesh is disappointing. We have "almost 126 widows" of men who died of CKD, Rajni Kumar said time limit, the village chief of Balliputtuga. The total population of the village is 3270, which means that almost 4% of its people died of the disease.

By screening the villagers in a van equipped with an ultrasound machine and other diagnostic equipment, Taduri and his colleagues came up with their estimated incidence of 15% or more in this region. Most people diagnosed with CKDU "did not have complaints that suggested a kidney problem," says Taduri. "But ... their creatinine was high." Sonographic examinations revealed that they had kidney "narrowed."

CKDU is so deadly in part because it is difficult to detect. "It is a silent killer," says AK Chakravarthy, nephrologist Nellore, Andhra Pradesh. In the early stages of the disease, people have no symptoms. "By the time they discover it is too late," he said. Their kidneys are already beyond repair, leading to high blood pressure, weakness, and other symptoms. Access to dialysis here remains limited, although the state government of Andhra Pradesh has added facilities in recent years. for many patients, death comes not long after their diagnosis.

Those lucky enough for dialysis survive for several years, but are unable to earn a living, pushing families deeper into poverty. its strength and stamina undermined by disease and dialysis, Kesava Rao can no longer provide for his family of five. his eldest son, now 20, had to take the place of his father. "He finished high school, then stopped studying," Rao said. "It is the main breadwinner of the family now."

In India, several research groups are on the trail of a cause. But every team used its own methods and tools, often in isolation, making it difficult to compare results. Taduri and Singh, for instance, both worked in Andhra Pradesh for years, and both have pursued the hypothesis that high levels of silica in drinking water might be responsible. Silica dust is known to damage the lungs and kidneys if inhaled, but we do not know what he does when ingested.

However, the two researchers had never met until recently. "I did not even know that this work was going on," Singh said on the work Taduri. While Singh thinks silica comes from pesticides, Taduri considers it leached into groundwater of bedrock. Singh admits researchers have benefited from collaboration. "We need to develop a coordinated approach."

This is true beyond India. as scientists and public health experts are finding that CKDU is a global disease or group of diseases, they cast a wider net for possible causes. "We have to look at this from a global perspective," says Weaver.

Some scientists 30 doctors and Indian and international public health experts are seated at a round table in any conference room at the Institute of Energy and Resources in New Delhi. The group is here for a workshop led by the CKD La Isla Foundation, a nonprofit group working with affected communities in Central America. The purpose of the January meeting: creating a global network of scientists studying the disease.

The first task for the network is to determine the prevalence, said Ben Caplin, nephrologist at University College London who works in Nicaragua. "We need to know where hotspots CKDnT," he said. "Are there environmental factors, professional and common social shared CKDnT hot spots?"

But participants differ . how to define the disease Caplin offers a working definition: "any alternative cause of CKD diagnosed by a medical professional, no diabetes, no high blood pressure." But Singh said the state could well be a collection diseases caused by different factors in different places. by insisting on a single definition, we "are already beginning to have a bias as to what the causes may be."

Neil Pearce of the London School of hygiene & Tropical Medicine, the only epidemiologist in the room, said screening for renal function can be done without making assumptions about the causes. "We try to find populations with high prevalence and low prevalence. This says nothing about the individual. "

Get a handle on prevalence will require a standard screening test, however. Caplin, Pearce and colleagues are developing a protocol that can be adapted for different populations: a blood test for kidney function, a urine test and a background questionnaire recording age, sex, occupation and income the participant. The team tries to keep things simple and inexpensive, Caplin said. "We do not want to put too complicated and people."

The team hopes to publish the protocol in peer review, so that scientists from any country can use to screen local or regional populations with their own funds. "I think the use of a simple protocol that will be affordable in different contexts would really shed light on the extent and global distribution of the disease," says Catharina Wesseling, a expert in occupational health and the environment at the Karolinska Institute in Stockholm.

Wesseling CKDnT studies in Central America, where it takes an even heavier toll in India. "Just look at mortality figures," said Jason Glaser La Isla. In Chichigalpa, Nicaragua, for example, "46% of all deaths in men are due to CKD," he said. "Sixty -Fifteen percent of men between 35 and 55 deaths are due to CKD. " By some estimates, the disease has killed at least 20,000 people in the region.

If the disease is the same striking India, research in Central America could narrow the search for a cause. Recent studies have reinforced the hypothesis that CKDU results of long hours in the heat of drinking water too little, leading to chronic dehydration. Last year, for example, a study by Wesseling and colleagues showed that the disease exists in Costa Rica, at least since the 1970s, but the mortality rate in Guanacaste province has climbed 4.4 to 100,000 men between 1970 and 1972 to 38.5 in 08 to 2012 with the expansion of sugarcane farms on an industrial scale. In another study, the same group showed that renal function cane cutters in a Nicaraguan community decreased by a single harvest period. "These people have a very frightening deterioration in renal function during the harvest period," says Wesseling.

a pilot study she and colleagues did last year hinted at how chronic dehydration done its damage. They found high levels of uric acid crystals in the urine of cane cutters, particularly at the ends their shifts. These crystals can hurt the kidneys, the researchers suggested. "This is an important mechanism that we had not thought of," said Richard Johnson, a nephrologist at the University of Colorado Denver and author of the study.

But the case is far from be closed. "I absolutely do not think the heat stress and dehydration are the only part of the story," Glaser said. "You see the different severity [of the disease] in different places." Like him, the most scientists are not yet rule out other factors.

Even before scientists know for sure what causes the disease, said Taduri communities can take action to reduce risks. Provide clean surface water sources for drinking, urging people to drink more water to work, and advising them to stay away from killers bread- will improve their health anyway, he says. In El Salvador, Glaser and his colleagues are working to develop a pilot study called the health efficiency program and workers, which requires frequent rest and hydration for workers.

Meanwhile, in CKDU affected communities in southern India, fear and frustration are on the rise. Now Taduri said, villagers in Andhra Pradesh refuse to come for screening, fearing stigmatization. When a man is diagnosed with kidney disease, "his family will feel it as a burden," said time limit, the village chief of Balliputtuga.

On a nearby farm, a group of men stand a peeling circle coconut. most are sweating in the sun by mid morning. Each stands on a blade longer than his forearm, his wooden handle firmly planted in the soil. They gather nuts coco a pile and each quickly pull on the blade, peeling away the thick hard crust, brown inner shell.

men talk as they work, and the conversation turns to their creatinine levels. "mine is 1.4," said a young man in his 30s. "mine is 1.3," another said. "One point nine." "Two." For half the men, the levels are either borderline or elevated. All work long hours under the sun, too little water to drink. Their legs and back hurt often when they go home at night, and they turn to painkillers or alcohol, even if they both know are bad for their kidneys.

men understand that they are at risk of disease chronic kidney, but believe they can not prevent it from progressing. the rest is not an option, it is said. "We have the disease, but we still have to work for a living."