PEDIATRICIAN'S POINT OF VIEW

Medical care for rural populations is an important problem facing the medical profession nationally and locally. The mechanism for solution lies in the existing American Medical Association and California Medical Association committees on rural medical service and further development of “local health councils.”Additional emphasis on training of physicians for general practice is essential through medical school graduate and postgraduate periods.The problem of providing additional adequately equipped and staffed hospitals must receive much consideration.Recognizing that passiveness invites aggressive non-medical agencies to foster bureaucratic dictation inimical to the practice of medicine, the rural physician must act through medical and community organizations to correct weaknesses in the structure of medical practice.     

“地衣”词考

本文考证了中国先秦时期到清末古籍中对“地衣”的解释;其中有共生学意义的“地衣”一词,是在清代李善兰的《植物学》一书中被提出的。     

Endpiece: Three different talks

ObjectivesTo characterise the information needs of family doctors by collecting the questions they asked about patient care during consultations and to classify these in ways that would be useful to developers of knowledge bases.DesignObservational study in which investigators visited doctors for two half days and collected their questions. Taxonomies were developed to characterise the clinical topic and generic type of information sought for each question.SettingEastern Iowa.ParticipantsRandom sample of 103 family doctors.ResultsParticipants asked a total of 1101 questions. Questions about drug prescribing, obstetrics and gynaecology, and adult infectious disease were most common and comprised 36% of all questions. The taxonomy of generic questions included 69 categories; the three most common types, comprising 24% of all questions, were “What is the cause of symptom X?” “What is the dose of drug X?” and “How should I manage disease or finding X?” Answers to most questions (702, 64%) were not immediately pursued, but, of those pursued, most (318, 80%) were answered. Doctors spent an average of less than 2 minutes pursuing an answer, and they used readily available print and human resources. Only two questions led to a formal literature search.ConclusionsFamily doctors in this study did not pursue answers to most of their questions. Questions about patient care can be organised into a limited number of generic types, which could help guide the efforts of knowledge base developers.

Key messages

• Questions that doctors have about the care of their patients could help guide the content of medical information sources and medical training
• In this study of US family doctors, participants frequently had questions about patient care but did not pursue answers to most questions (64%)
• On average, participants spent less than 2 minutes seeking an answer to a question
• The most common resources used to answer questions included textbooks and colleagues; formal literature searches were rarely performed
• The most common generic questions were “What is the cause of symptom X?” “What is the dose of drug X?” and “How should I manage disease or finding X?”

     

Goiter in Tibetan Medicine

The visit of two Tibetan physicians provided a unique opportunity to gain insight into a practice of medicine very different from that of Western civilization. Initial discussions indicated that the practice of medicine and mysticism were inextricably interwoven in the Tibetan culture. Accordingly, the focus of the study was directed to goiter, which is both common in the Himalayas and easy to define.In Tibetan medical practice, illness is considered to be derived from both proximate and distant causes. Three humors, “wind,” “bile,” and “phlegm” are thought to be responsible for normal mental and physical functions when in balance, but disease when out of balance. Goiter was thought to be due to an imbalance of these humors. The Western discovery that endemic goiter in the Himalayas was due to iodine deficiency explained the proximate cause but did not explain why some individuals have goiter and others do not in the same iodine deficient village.     

How Often Are Antibiotic-Resistant Bacteria Said to “Evolve” in the News?

Media plays an important role in informing the general public about scientific ideas. We examine whether the word “evolve,” sometimes considered controversial by the general public, is frequently used in the popular press. Specifically, we ask how often articles discussing antibiotic resistance use the word “evolve” (or its lexemes) as opposed to alternative terms such as “emerge” or “develop.” We chose the topic of antibiotic resistance because it is a medically important issue; bacterial evolution is a central player in human morbidity and mortality. We focused on the most widely-distributed newspapers written in English in the United States, United Kingdom, Canada, India, and Australia. We examined all articles that focused primarily on the evolution of antibiotic resistance, were published in 2014 or earlier, and were accessible in online archives, for a total of 1639 articles. The total years examined per newspaper ranged from 5 to 37 years with a median of 27 years, and the overall range was 1978–2014. We quantified how many articles included the term “evolve” and analyzed how this varied with newspaper, country, and time. We found that an overall rate of 18% of articles used the term “evolve” but with significant variation among countries. Newspapers in the United Kingdom had the highest rate (24%), more than double of those in India (9%), the country with the lowest rate. These frequencies were lower than those found in scientific papers from both evolutionary journals and biomedical journals. There were no statistically significant changes in frequency and no trends when “evolve” usage was compared against variables such as newspaper circulation, liberal/conservative bias, time, and state evolution acceptance in U.S. newspapers. This study highlights the globally low usage of the word “evolve” in the popular press. We suggest this low usage may affect public understanding and acceptance of evolutionary concepts.     

Health Risk or Resource? Gradual and Independent Association between Self-Rated Health and Mortality Persists Over 30 Years

Background

Poor self-rated health (SRH) is associated with increased mortality. However, most studies only adjust for few health risk factors and/or do not analyse whether this association is consistent also for intermediate categories of SRH and for follow-up periods exceeding 5–10 years. This study examined whether the SRH-mortality association remained significant 30 years after assessment when adjusting for a wide range of known clinical, behavioural and socio-demographic risk factors.

Methods

We followed-up 8,251 men and women aged ≥16 years who participated 1977–79 in a community based health study and were anonymously linked with the Swiss National Cohort (SNC) until the end of 2008. Covariates were measured at baseline and included education, marital status, smoking, medical history, medication, blood glucose and pressure.

Results

92.8% of the original study participants could be linked to a census, mortality or emigration record of the SNC. Loss to follow-up 1980–2000 was 5.8%. Even after 30 years of follow-up and after adjustment for all covariates, the association between SRH and all-cause mortality remained strong and estimates almost linearly increased from “excellent” (reference: hazard ratio, HR 1) to “good” (men: HR 1.07 95% confidence interval 0.92–1.24, women: 1.22, 1.01–1.46) to “fair” (1.41, 1.18–1.68; 1.39, 1.14–1.70) to “poor”(1.61, 1.15–2.25; 1.49, 1.07–2.06) to “very poor” (2.85, 1.25–6.51; 1.30, 0.18–9.35). Persons answering the SRH question with “don''t know” (1.87, 1.21–2.88; 1.26, 0.87–1.83) had also an increased mortality risk; this was pronounced in men and in the first years of follow-up.

Conclusions

SRH is a strong and “dose-dependent” predictor of mortality. The association was largely independent from covariates and remained significant after decades. This suggests that SRH provides relevant and sustained health information beyond classical risk factors or medical history and reflects salutogenetic rather than pathogenetic pathways.     

A Likelihood-Based Approach to Identifying Contaminated Food Products Using Sales Data: Performance and Challenges

Foodborne disease outbreaks of recent years demonstrate that due to increasingly interconnected supply chains these type of crisis situations have the potential to affect thousands of people, leading to significant healthcare costs, loss of revenue for food companies, and—in the worst cases—death. When a disease outbreak is detected, identifying the contaminated food quickly is vital to minimize suffering and limit economic losses. Here we present a likelihood-based approach that has the potential to accelerate the time needed to identify possibly contaminated food products, which is based on exploitation of food products sales data and the distribution of foodborne illness case reports. Using a real world food sales data set and artificially generated outbreak scenarios, we show that this method performs very well for contamination scenarios originating from a single “guilty” food product. As it is neither always possible nor necessary to identify the single offending product, the method has been extended such that it can be used as a binary classifier. With this extension it is possible to generate a set of potentially “guilty” products that contains the real outbreak source with very high accuracy. Furthermore we explore the patterns of food distributions that lead to “hard-to-identify” foods, the possibility of identifying these food groups a priori, and the extent to which the likelihood-based method can be used to quantify uncertainty. We find that high spatial correlation of sales data between products may be a useful indicator for “hard-to-identify” products.     

围小丛壳Glomerella cingulata子囊孢子交配繁殖、生物学特性及致病性

炭疽叶枯病（Glomerella leaf spot）是我国苹果上新发现的一种病害。为了解围小丛壳Glomerella cingulata子囊孢子的交配方式、生物学特性和致病性,从安徽砀山、山东牟平等地采集病害样品,经分离培养和纯化获得单孢菌株。在适宜条件下单孢菌株可产生子囊和子囊孢子,经过毛细管破子囊壁后单孢分离,获得12个子囊,每个子囊有8个子囊孢子。其中10个子囊中有4个“正”孢子（+）和4个“负”孢子（-）,2个子囊中只有“负”孢子。子囊孢子单孢菌株培养72h,“正”菌株菌落白色,以营养生长为主;“负”菌株菌落灰白色,直径略小于正菌株,菌丝稀疏,边缘菌丝白色,中部有大量橙色的分生孢子堆。“正”、“负”菌株异宗配合后,可产生大量可育子囊壳;单独的“正”菌株有性生殖产生稀疏丛簇状的可育子囊壳;单个的“负”菌株只能产生分散且不育的子囊壳。“正”、“负”菌株菌落的生长速度没有差异,对温度、营养、光照和pH值的敏感性也没有差异,但“正”、“负”菌株的致病性存在差异。正菌株的有性生殖没有导致rDNA-ITS、β-tubulin基因碱基序列变异。     

What doesn't kill you makes you dumber. Strengthening the link between infectious disease, intelligence and personality

A causal link between childhood exposure to disease and the development of intelligence would have major implications for public health and international development programmes.The idea that infectious disease during childhood affects the developing brain to impact intelligence has been around for decades. Recent evidence from more rigorous studies, which have controlled carefully for other factors such as nutrition and education, has strengthened the case. If these new epidemiological and molecular studies really do confirm a clear link between childhood infection and intelligence, the consequences for health policy and development assistance could be profound. The results could mandate an increased focus not only on eradicating or controlling infectious diseases, but also on reducing their impact on children in the absence of cures or vaccines.If these … studies do show a clear link between childhood infection and intelligence, the consequences for health policy and development assistance could be profoundYet, even in the light of new evidence, it is hard to unravel causes from effects, and the debate continues over which diseases are most responsible, along with the precise physiological and molecular mechanisms involved. There is no shortage of theories to explain why infectious disease seems to have so profound an effect on intelligence, and, as a result, on the intellectual and economic performance of whole nations or regions. The stage is set for more studies to drill down into neurological and cognitive mechanisms: to explain why the prevalence of infectious disease is a reliable predictor of intelligence at the population level; to differentiate between the impact of various pathogens; and to identify the evolutionary rationale of these links. There is also mounting evidence that some parasites can alter their host''s personality through mechanisms evolved to modify their host''s behaviour to their own advantage, which could explain environmental risk factors for mental disorders, such as schizophrenia.After a few intermittent references earlier last century, the US economist Andrew Kamarck made the first attempt to link infectious disease with a nation''s performance during the 1970s [1]. Kamarck identified the interplay of three factors—temperature, humidity and infectious diseases—on the economic performance of nations through their impact on vitality and intellectual attainment.Somewhat surprisingly, both economists and biologists neglected Kamarck''s findings that link infectious disease and either intelligence or performance at a population level for another three decades. Eventually, Christopher Eppig and colleagues at the University of New Mexico in Albuquerque, USA, published a seminal paper in 2010, which reported a strong correlation between the prevalence of infectious disease in a country and intelligence as measured by supposedly culturally independent IQ tests [2]. In the past, other environmental factors, such as average temperature, have been shown to affect intelligence, but in Eppig''s study, infectious disease seems to trump these. The country with the highest average IQ of all, Singapore, is hot and humid, but has the world''s lowest rates of infectious disease largely because of excellent healthcare.The Eppig study also offers a plausible explanation for the so-called Flynn Effect, named after the political scientist James Flynn who described and promoted the apparent sustained and significant increase in average intelligence in many developed nations during the past half-century or more [3]. “Our research suggests that infectious disease may be the most important factor influencing IQ,” Eppig confirmed. “Infectious disease has the strongest correlation with average IQ, and the largest independent contribution when other factors are controlled.” The researchers found that the correlation between average IQ and infectious disease at the cross-national level is between −0.76 and −0.82; 0 would equate to no correlation and −1 would be total correlation. The results indicate a high degree of correlation, and, just as importantly, the study determined that the probability of this correlation having occurred by chance was incredibly low.…both economists and biologists neglected Kamarck''s findings that link infectious disease and either intelligence or performance at a population level for another three decadesThe intelligence scores were largely taken from an earlier study conducted by UK psychologist Richard Lynn and Finnish political scientist Jaan Mikk, which analysed IQ scores from 113 countries [4], and the data on infectious diseases were provided by the World Health Organization. Given that both sets of data were openly available, it was easy for other groups to perform their own analyses to either corroborate or refute Eppig''s findings. Chris Hassall and colleagues at Carleton University in Ottawa, Canada, have done just such a follow up to identify or eliminate any statistical artefacts that might weaken or cast doubt on the findings [5]. One of the significant possible artefacts for which Hassall controlled is a phenomenon known as autocorrelation, which is the tendency for two sets of data to seem to be linked just because they have similar spatial patterns of variation. “Having reanalysed the data, I am fairly convinced that there is a strong correlation between the health impacts of parasites and IQ,” Hassall confirmed. In fact, Eppig himself suggested that Hassall''s results were stronger than his own. “They found that, when controlling for spatial autocorrelation, infectious disease was an even better predictor of average national IQ than our own analysis had found,” he commented.Meanwhile, Eppig has published another study analysing the correlation between disease and intelligence within a single country [6]. He chose the USA because there is good data available for individual states, with sufficient variation across the country as a whole to provide the necessary range of data. This study was conducted partly in response to criticism of the first one on the grounds that national differences in culture and education might not have been fully filtered out. By studying just one country with a significant degree of cultural and educational harmony, Eppig hoped to provide an even more convincing case for the link between infectious disease and IQ.According to Michael Woodley, who has been studying the link between infectious disease and intelligence at the University of Surrey, UK, the correlation found in the US study is not as strong, but is still significant. “They found a weaker set of relationships, but infectious disease was still a potent predictor of cross state variance in IQ,” Woodley said, but added that these studies beg the question of cause and effect. “The question is, have they found evidence that infectious disease has a causal influence on IQ, or is it the case that cross national patterns of IQ affect disease ecology?” he explained. The suggestion is that intelligence itself can affect the prevalence of disease. “My cautious take is that it''s a bit of both.”Hassall conceded that his and the other studies have only identified a correlation between infectious disease and intelligence, albeit a strong one, and not a causal link. But he added that there were plausible underlying physiological explanations for the link, although as yet there is no definitive proof for any.“We can only speculate about the possible causal links,” agreed Joachim Kurtz, a group leader whose lab works on animal evolutionary ecology at the Westfälische Wilhelms–Universität Münster in Germany. “There are at least two non-exclusive possibilities: firstly, given that the brain needs a lot of energy, the energetic costs of parasitic infection and immune defense may provide a mechanistic explanation for the correlation […] a second, slightly frightening and more direct possibility is that parasite manipulation might make hosts stupid.”The first possibility could be caused by the need to reroute energy from the brain to repair tissue damaged by parasites, or by energy lost through malnutrition as a result of diarrhoea, vomiting, or diminished absorption through the digestive tract. It could also result from the parasite accessing cellular or macromolecular resources at the expense of the developing brain, or by the energy cost of maintaining a heightened immune response. All these factors might decrease the energy and nutrients available to the developing brain and cause reduced cognitive capability.The second possibility cited by Kurtz might involve direct damage to, or alteration of, neurological mechanisms, perhaps deliberately engineered by the parasite for its advantage. The case of rabies is an extreme example of an infection in which the parasite, a virus infecting nerve cells and causing acute encephalitis, changes its host''s behaviour to increase the chance of its spreading, in this case causing the host to bite others and spread the virus through saliva.But there is growing evidence that parasites causing chronic infections can alter behaviour in more subtle ways to increase the chance of transmissionBut there is growing evidence that parasites causing chronic infections can alter behaviour in more subtle ways to increase the chance of transmission. Kurtz cited the case of the protozoa Toxoplasma gondii, referring to a recent paper by Czech parasitologist Jaroslav Flegr from Charles University, Prague, which found that infection can trigger various psychiatric and neurological diseases, including schizophrenia, in people with genetic predispositions [7].“Dozens of studies published in the past 20 years clearly show that toxoplasmosis is responsible for a large number of cases of schizophrenia,” Flegr noted. “Recent results, some of them published by our group, show that toxoplasmosis-associated schizophrenia has more severe clinical symptoms than other kinds of schizophrenia.” Such symptoms were associated with noticeable changes in brain morphology and included impaired reaction times as well as personality changes, Flegr added. Together, these changes were found to increase the risk not just of suicide but also accidental injury or death [8,9]. Adding these factors together, Flegr estimated that latent toxoplasmosis is indirectly responsible for more than one million deaths per year, which would make it the world''s second most dangerous protozoan parasite after malaria, albeit indirectly killing its victims.In the case of T. gondii the same ‘chicken and egg'' question arises of whether infection causes the psychiatric disorders, or whether psychiatric disorders make infection more likely. According to Flegr, there is molecular evidence to support the hypothesis that infection causes psychiatric disorders. “It has been known for a long time that toxoplasmosis increases the concentration of dopamine in the infected brain,” he said. “In 2009 it was shown that the genome of Toxoplasma contains genes for two rate-limiting enzymes for synthesis of dopamine in the brain tissue [10]. Another study then demonstrated that large amounts of this neurotransmitter are synthesized in cysts of Toxoplasma in the brains of infected laboratory animals [11].”There has been growing evidence that such disruption in dopamine production does increase the risk of developing schizophrenia [12]. Flegr speculated that this manipulation of the host''s neurotransmitter production, primarily an increase in dopamine combined with a decrease in serotonin, has its roots in animal evolution. “At least some of the changes are most probably results of manipulative activity of the parasite aimed at increasing efficiency of transmission from an intermediate animal to definitive host by predation,” he explained. “Some are probably just side effects of chronic disease.”…Flegr estimated that latent toxoplasmosis is indirectly responsible for more than one million deaths per year […] the world''s second most dangerous protozoan parasite…Although infection by T. gondii is particularly common in Africa and South America, Flegr noted that it also has a high incidence in cooler and drier regions, being associated with the consumption of raw vegetables and raw meat. The latter factor perhaps explains its high prevalence in France and Germany, where 40–50% of the population are infected, compared with less than 20% in the UK and USA. These are large figures nonetheless, so the recent findings highlight the urgency of further research to understand the genetic risk factors that predispose infected individuals to neurological illness.“…our hypothesis predicts that the infections that cause the greatest amount of energy to be diverted away from the brain will have the largest detrimental effect…”When it comes to the less clearly defined issue of intelligence, researchers are just beginning to identify candidate genes in the host. Among the best known is microcephalin, a gene known to regulate brain size, but the precise role of which in intelligence has yet to be explained. However Heiner Rindermann from the Institute of Psychology at Chemnitz, Germany, has found evidence that high levels of microcephalin within a population seem to be associated with low levels of disease and higher intelligence [13]. “Microcephalin does not predict IQ at the individual level, but it does at ecological scales,” Rindermann said. The reason the operation of microcephalin can only be seen at the population level, he explained, is that it does not provide any physiological protection against disease but does make people more sensitive to dirt and more likely to indulge in hygienic behaviour, which affects all people in the vicinity.“The role of infectious disease burdens as the principal mediator of this ecological relationship suggests that populations exhibiting high levels of microcephalin were better able to cope with historical disease burdens,” Rindermann reasoned. “We believe that microcephalin might have encoded for disgust sensitivity, hence more sensitive populations transitioning out of the hunter-gatherer mode of subsistence and into the agrarian one could have carried on growing such that the frequency of IQ-enhancing mutations could have increased via runaway gene-culture co-evolution.”This three-way link between microcephalin, disease and intelligence remains speculative, but the overall association between infectious parasites and broad cognitive behaviour is increasingly well established. It is not yet clear, though, which diseases are the main culprits, with a few exceptions such as T. gondii for psychotic disorders. Differentiating between the different pathogens is one of the main targets for research in the field, according to Eppig. “We have not done empirical work on this question yet, although we have a project in the works, but our hypothesis predicts that the infections that cause the greatest amount of energy to be diverted away from the brain will have the largest detrimental effect,” he said. “This means that long-term, chronic, infections are more likely to have a greater detrimental effect on the brain than short-term infections. In particular, we predict that parasites causing diarrheal diseases, malaria and tuberculosis, to name a few, will have the largest effect.”However, Woodley commented there is evidence that sexually transmitted diseases rather than diseases of the intestinal or respiratory tracts have the largest impact on intelligence. But these diseases are often chronic, although Woodley suggested that the correlation could simply result from people with higher IQs being less likely to catch them.All this research paints an increasingly detailed picture of how infectious diseases and the development of intelligence are linked; but there is clearly much more to be done to unravel the underlying mechanisms. The evidence already accumulated indicates that continuing efforts to eradicate disease in the developing world should be increased. However, as Hassall pointed out, the societal case for doing that stands on its own and does not need to be associated with intelligence.     

Genomes, race and health. Racial profiling in medicine might just be a stepping stone towards personalized health care

Considering a patient''s ethnic background can make some diagnoses easier. Yet, ‘racial profiling'' is a highly controversial concept and might soon be replaced by the advent of individualized medicine.In 2005, the US Food and Drug Administration (FDA; Bethesda, MD, USA) approved BiDil—a combination of vasodilators to treat heart failure—and hailed it as the first drug to specifically treat an ethnic group. “Approval of a drug to treat severe heart failure in self-identified black population is a striking example of how a treatment can benefit some patients even if it does not help all patients,” announced Robert Temple, the FDA''s Director of Medical Policy. “The information presented to the FDA clearly showed that blacks suffering from heart failure will now have an additional safe and effective option for treating their condition” (Temple & Stockbridge, 2007). Even the National Medical Association—the African-American version of the American Medical Association—advocated the drug, which was developed by NitroMed, Inc. (Lexington, MA, USA). A new era in medicine based on racial profiling seemed to be in the offing.By January 2008, however, the ‘breakthrough'' had gone bust. NitroMed shut down its promotional campaign for BiDil—a combination of the vasodilators isosorbide dinitrate, which affects arteries and veins, and hydralazine hydrochloride, which predominantly affects arteries. In 2009, it sold its BiDil interests and was itself acquired by another pharmaceutical company.In the meantime, critics had largely discredited the efforts of NitroMed, thereby striking a blow against the drug if not the concept of racial profiling or race-based medicine. Jonathan Kahn, a historian and law professor at Hamline University (St Paul, MN, USA), described the BiDil strategy as “a leap to genetics.” He demonstrated that NitroMed, motivated to extend its US patent scheduled to expire in 2007, purported to discover an advantage for a subpopulation of self-identified black people (Kahn, 2009). He noted that NitroMed conducted a race-specific trial to gain FDA approval, but, as there were no comparisons with other populations, it never had conclusive data to show that BiDil worked in black people differently from anyone else.“If you want to understand heart failure, you look at heart failure, and if you want to understand racial disparities in conditions such as heart failure or hypertension, there is much to look at that has nothing to do with genetics,” Kahn said, adding “that jumping to race as a genetic construct is premature at best and reckless generally in practice.” The USA, he explained, has a century-old tradition of marketing to racial and ethnic groups. “BiDil brought to the fore the notion that you can have ethnic markets not only in things like cigarettes and food, but also in pharmaceuticals,” Kahn commented.“BiDil brought to the fore the notion that you can have ethnic markets not only in things like cigarettes and food, but also in pharmaceuticals”However, despite BiDil''s failure, the search for race-based therapies and diagnostics is not over. “What I have found is an increasing, almost exponential, rise in the use of racial and ethnic categories in biotechnology-related patents,” Kahn said. “A lot of these products are still in the pipeline. They''re still patent applications, they''re not out on the market yet so it''s hard to know how they''ll play out.”The growing knowledge of the human genome is also providing new opportunities to market medical products aimed at specific ethnic groups. The first bumpy steps were taken with screening for genetic risk factors for breast cancers. Myriad Genetics (Salt Lake City, UT, USA) holds broad patents in the USA for breast-cancer screening tests that are based on mutations of the BRCA1 and BRCA2 genes, but it faced challenges in Europe, where critics raised concerns about the high costs of screening.The growing knowledge of the human genome is also providing new opportunities to market medical products aimed at specific ethnic groupsThe European Patent Office initially granted Myriad patents for the BRCA1 and BRCA2-based tests in 2001, after years of debate. But it revoked the patent on BRCA1 in 2005, which was again reversed in 2009. In 2005 Myriad decided to narrow the scope of BRCA2 testing on the basis of ethnicity. The company won a patent to predict breast-cancer risk in Ashkenazi Jewish women on the basis of BRCA2 mutations, which occur in one in 100 of these women. Physicians offering the test are supposed to ask their patients whether they are in this ethnic group, and then pay a fee to Myriad.Kahn said Myriad took this approach to package the test differently in order to protect its financial interests. However, he commented, the idea of ethnic profiling by asking women whether they identify themselves as Ashkenazi Jewish and then paying extra for an ‘ethnic'' medical test did not work in Europe. “It''s ridiculous,” Kahn commented.After the preliminary sequence of the human genome was published a decade ago, experts noted that humans were almost the same genetically, implying that race was irrelevant. In fact, the validity of race as a concept in science—let alone the use of the word—has been hotly debated. “Race, inasmuch as the concept ought to be used at all, is a social concept, not a biological one. And using it as though it were a biological one is as a much an ethical problem as a scientific problem,” commented Samia Hurst, a physician and bioethicist at Geneva University Medical School in Switzerland.​Switzerland.Open in a separate window© Monalyn Gracia/CorbisCiting a popular slogan: “There is no gene for race,” she noted, “there doesn''t seem to be a single cluster of genes that fits with identification within an ethnic group, let alone with disease risks as well. We''re also in an increasingly mixed world where many people—and I count myself among them—just don''t know what to check on the box. If you start counting up your grandparents and end up with four different ethnic groups, what are you going to do? So there are an increasing number of people who just don''t fit into those categories at all.”Still, some dismiss criticism of racial profiling as political correctness that could potentially prevent patients from receiving proper care. Sally Satel, a psychiatrist in Washington, DC, USA, does not shy away from describing herself as a racially profiling physician and argues that it is good medicine. A commentator and resident scholar at the nonpartisan conservative think tank, the American Enterprise Institute (Washington, DC, USA), Satel wrote the book PC, M.D.: How Political Correctness is Corrupting Medicine. “In practicing medicine, I am not color blind. I take note of my patient''s race. So do many of my colleagues,” she wrote in a New York Times article entitled “I am a racially profiling doctor” (Satel, 2002).…some dismiss criticism of racial profiling as political correctness that could potentially prevent patients from receiving proper careSatel noted in an interview that it is an undeniable fact that black people tend to have more renal disease, Native Americans have more diabetes and white people have more cystic fibrosis. She said these differences can help doctors to decide which drugs to prescribe at which dose and could potentially lead researchers to discover new therapies on the basis of race.Satel added that the mention of race and medicine makes many people nervous. “You can dispel that worry by taking pains to specify biological lineage. Simply put, members of a group have more genes in common than members of the population at large. Some day geneticists hope to be able to conduct genomic profiles of each individual, making group identity irrelevant, but until then, race-based therapeutics has its virtues,” she said. “Denying the relationship between race and medicine flies in the face of clinical reality, and pretending that we are all at equal risk for health problems carries its own dangers.”However, Hurst contended that this approach may be good epidemiology, rather than racial profiling. Physicians therefore need to be cautious about using skin colour, genomic data and epidemiological data in decision making. “If African Americans are at a higher risk for hypertension, are you not going to check for hypertension in white people? You need to check in everyone in any case,” she commented.Hurst said European physicians, similarly to their American colleagues, deal with race and racial profiling, albeit in a different way. “The way in which we struggle with it is strongly determined by the history behind what could be called the biases that we have. If you have been a colonial power, if the past is slavery or if the past or present is immigration, it does change some things,” she said. “On the other hand, you always have the difficulty of doing fair and good medicine in a social situation that has a kind of ‘them and us'' structure. Because you''re not supposed to do medicine in a ‘them and us'' structure, you''re supposed to treat everyone according to their medical needs and not according to whether they''re part of ‘your tribe'' or ‘another tribe''.”Indeed, social factors largely determine one''s health, rather than ethnic or genetic factors. August A. White III, an African-American orthopaedic surgeon at Harvard Medical School (Boston, MA, USA) and author of the book Seeing Patients: Unconscious Bias In Health Care, noted that race is linked to disparities in health care in the USA. A similar point can be made in Europe where, for example, Romani people face discrimination in several countries.White said that although genetic research shows that race is not a scientific concept, the way people are labelled in society and how they are treated needs to be taken into account. “It''d be wonderful at some point if we can pop one''s key genetic information into a computer and get a printout of which medications are best of them and which doses are best for them,” he commented. “In the meantime though, I advocate careful operational attempts to treat everyone as human beings and to value everyone''s life, not devalue old people, or devalue women, or devalue different religious faiths, etc.”Notwithstanding the scientific denunciation, a major obstacle for the concept of racial profiling has been the fact that the word ‘race'' itself is politically loaded, as a result of, among other things, the baggage of eugenics and Nazi racism and the legacies of slavery and colonialism. Richard Tutton, a sociologist at Lancaster University in the UK, said that British scientists he interviewed for a Wellcome Trust project a few years ago prefer the term ethnicity to race. “Race is used in a legal sense in relation to inequality, but certainly otherwise, ethnicity is the preferred term, which obviously is different to the US” he said. “I remember having conversations with German academics and obviously in Germany you couldn''t use the R-word.”Jan Helge Solbakk, a physician, theologian and medical ethicist at the University of Oslo in Norway, said the use of the term race in Europe is a non-starter because it makes it impossible for the public and policy-makers to communicate. “I think in Europe it would be politically impossible to launch a project targeting racial differences on the genetic level. The challenge is to find not just a more politically correct concept, but a genetically more accurate concept and to pursue such research questions,” he said. According to Kahn, researchers therefore tend to refer to ethnicity rather than race: “They''re talking about European, Asian and African, but they''re referring to it as ethnicity instead of race because they think somehow that''s more palatable.”Regardless, race-based medicine might just be a stepping stone towards more refined and accurate methods, with the advent of personalized medicine based on genomics, according to Leroy Hood, whose work has helped to develop tools to analyse the human genome. The focus of his company—the Institute for Systems Biology (Seattle, WA, USA)—is to identify genetic variants that can inform and help patients to pioneer individualized health care.“Race as a concept is disappearing with interbreeding,” Hood said. “Race distinction is going to slowly fade away. We can use it now because we have signposts for race, which are colour, fairness, kinkiness of hair, but compared to a conglomeration of things that define a race, those are very few features. The race-defining features are going to be segregating away from one another more and more as the population becomes racially heterogeneous, so I think it''s going to become a moot point.”Hood instead advocates “4P” health care—“Predictive, Personalized, Preventive and Participatory.” “My overall feeling about the race-based correlations is that it is far more important to think about the individual and their individual unique spectra of health and wellness,” he explained. “I think we are not going to deal in the future with racial or ethnic populations, rather medicine of the future is going to be focused entirely on the individual.”Yet, Arthur Caplan, Director of the Center for Bioethics at the University of Pennsylvania (Philadelphia, PA, USA), is skeptical about the prospects for both race-based and personalized medicine. “Race-based medicine will play a minor role over the next few years in health care because race is a minor factor in health,” he said. “It''s not like we have a group of people who keel over dead at 40 who are in the same ethnic group.”Caplan also argued that establishing personalized genomic medicine in a decade is a pipe dream. “The reason I say that is it''s not just the science,” he explained. “You have to redo the whole health-care system to make that possible. You have to find manufacturers who can figure out how to profit from personalized medicine who are both in Europe and the United States. You have to have doctors that know how to prescribe them. It''s a big, big revamping. That''s not going to happen in 10 years.”Hood, however, is more optimistic and plans to advance the concept with pilot projects; he believes that Europe might be the better testing ground. “I think the European systems are much more efficient for pioneering personalized medicine than the United States because the US health-care system is utterly chaotic. We have every combination of every kind of health care and health delivery. We have no common shared vision,” he said. “In the end we may well go to Europe to persuade a country to really undertake this. The possibility of facilitating a revolution in health care is greater in Europe than in the United States.”     

The new role of the hospital emergency department

The volume of medical services delivered within hospital emergency departments in the City of Saskatoon is increasing rapidly. These probably are not “new” medical services but rather represent a transfer of “old” services to the emergency departments from other sites where they were previously rendered. The visit to the emergency department is initiated more often by the patient than the doctor and once there the patient is treated in a relatively short period of time. The illnesses so managed do not have a diagnostic, therapeutic or prognostic uniformity but rather are characterized by their acute and totally unexpected onset. This acute and non-programmable nature of the illness makes it difficult to deliver the service in a physician''s office where the appointment system prevails and efficiently deals with the great majority of his patients. Data to determine whether or not this is a desirable development have not yet been obtained but it is clear that in its present usage the emergency department must be thought of as a facility which not only provides exceptional diagnostic and therapeutic equipment but as one which also provides a treatment facility without prior appointment available at any hour of the day or night.     

Practitioner attitudes in the United States and United Kingdom toward decisions at the end of life: are medical ethicists out of touch?

Objective To assess whether UK and US health care professionals share the views of medical ethicists about medical futility, withdrawing or withholding treatment, ordinary or extraordinary interventions, and the doctrine of double effect. Design, subjects, and setting Answers to a 138-item attitudinal questionnaire completed by 469 UK nurses studying the Open University course on “Death and Dying” were compared with those of a similar questionnaire administered to 759 US nurses and 687 US physicians taking the Hastings Center course on “Decisions Near the End of Life.” Results Practitioners accept the relevance of concepts widely disparaged by bioethicists: double effect, medical futility, and the distinctions between heroic and ordinary interventions and withholding and withdrawing treatment. Within the UK nurses'' group, the responses of a “rationalist” axis of respondents who describe themselves as having “no religion” are closer to the bioethics consensus on withholding and withdrawing treatment. Conclusions Professionals'' beliefs differ substantially from the recommendations of their professional bodies and from majority opinion in bioethics. Bioethicists should be cautious about assuming that their opinions will be readily accepted by practitioners.     

Crystal structure of a trimeric form of the KV7.1 (KCNQ1) A‐domain tail coiled‐coil reveals structural plasticity and context dependent changes in a putative coiled‐coil trimerization motif

Coiled-coils are widespread protein–protein interaction motifs typified by the heptad repeat (abcdefg)_n in which “a” and “d” positions are hydrophobic residues. Although identification of likely coiled-coil sequences is robust, prediction of strand order remains elusive. We present the X-ray crystal structure of a short form (residues 583–611), “Q1-short,” of the coiled-coil assembly specificity domain from the voltage-gated potassium channel Kv7.1 (KCNQ1) determined at 1.7 Å resolution. Q1-short lacks one and half heptads present in a previously studied tetrameric coiled-coil construct, Kv7.1 585–621, “Q1-long.” Surprisingly, Q1-short crystallizes as a trimer. In solution, Q1-short self-assembles more poorly than Q1-long and depends on an R-h-x-x-h-E motif common to trimeric coiled-coils. Addition of native sequences that include “a” and “d” positions C-terminal to Q1-short overrides the R-h-x-x-h-E motif influence and changes assembly state from a weakly associated trimer to a strongly associated tetramer. These data provide a striking example of a naturally occurring amino sequence that exhibits context-dependent folding into different oligomerization states, a three-stranded versus a four-stranded coiled-coil. The results emphasize the degenerate nature of coiled-coil energy landscapes in which small changes can have drastic effects on oligomerization. Discovery of these properties in an ion channel assembly domain and prevalence of the R-h-x-x-h-E motif in coiled-coil assembly domains of a number of different channels that are thought to function as tetrameric assemblies raises the possibility that such sequence features may be important for facilitating the assembly of intermediates en route to the final native state.     

Neglected diseases in the news: a content analysis of recent international media coverage focussing on leishmaniasis and trypanosomiasis

Background

Although the pharmaceutical industry''s “neglect” of neglected tropical diseases (NTDs) has been investigated, no study evaluating media coverage of NTDs has been published. Poor media coverage exacerbates the neglect. This study aimed to investigate, describe, and analyse international media coverage of “neglected diseases” in general and three specific NTDs—African trypanosomiasis, leishmaniasis, and Chagas disease—from 1 January 2003 to 1 June 2007.

Methods

Archives of 11 leading international, English-language media were searched. A content analysis was done, coding for media organisation, date, author, type of report, slant, themes, and “frames”. Semi-structured interviews with journalists and key informants were conducted for further insight.

Principal Findings

Only 113 articles in a 53-month time period met the inclusion criteria, with no strong trends or increases in coverage. Overall, the BBC had the highest coverage with 20 results, followed by the Financial Times and Agence France Presse. CNN had the least coverage with one result. The term “neglected diseases” had good media currency and “sleeping sickness” was far more widely used than trypanosomiasis. The disease most covered was leishmaniasis and the least covered was Chagas. Academic researchers were most commonly quoted as a main source, while the World Health Organization (WHO) and pharmaceutical industry were the least quoted. Journalists generally agreed NTDs had not been adequately covered, but said a lack of real news development and the need to cater to domestic audiences were major obstacles for NTD reporting. All journalists said health agencies, particularly WHO, were not communicating adequately about the burden of NTDs.

Conclusions

Public health agencies need to raise priority for NTD advocacy. Innovative strategies, such as reporting grants or creating a network of voices, may be needed.     

A cost-effectiveness analysis of "test" versus "treat" patients hospitalized with suspected influenza in Hong Kong

Background

Seasonal and 2009 H1N1 influenza viruses may cause severe diseases and result in excess hospitalization and mortality in the older and younger adults, respectively. Early antiviral treatment may improve clinical outcomes. We examined potential outcomes and costs of test-guided versus empirical treatment in patients hospitalized for suspected influenza in Hong Kong.

Methods

We designed a decision tree to simulate potential outcomes of four management strategies in adults hospitalized for severe respiratory infection suspected of influenza: “immunofluorescence-assay” (IFA) or “polymerase-chain-reaction” (PCR)-guided oseltamivir treatment, “empirical treatment plus PCR” and “empirical treatment alone”. Model inputs were derived from literature. The average prevalence (11%) of influenza in 2010–2011 (58% being 2009 H1N1) among cases of respiratory infections was used in the base-case analysis. Primary outcome simulated was cost per quality-adjusted life-year (QALY) expected (ICER) from the Hong Kong healthcare providers'' perspective.

Results

In base-case analysis, “empirical treatment alone” was shown to be the most cost-effective strategy and dominated the other three options. Sensitivity analyses showed that “PCR-guided treatment” would dominate “empirical treatment alone” when the daily cost of oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the threshold of willingness-to-pay, “empirical treatment alone” and “PCR-guided treatment” were cost-effective 97% and 3% of time, respectively, in 10,000 Monte-Carlo simulations.

Conclusions

During influenza epidemics, empirical antiviral treatment appears to be a cost-effective strategy in managing patients hospitalized with severe respiratory infection suspected of influenza, from the perspective of healthcare providers in Hong Kong.     

Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials

ObjectiveTo summarise the effect of primary prevention with lipid lowering drugs on coronary heart disease events, coronary heart disease mortality, and all cause mortality.DesignMeta-analysis.IdentificationSystematic search of the Medline database from January 1994 to June 1999 for English language studies examining drug treatment for lipid disorders (use of the MeSH terms “hyperlipidemia” and “anticholesteremic agents,” keyword searches for individual drug names, and a search strategy for identifying randomised trials to capture relevant articles); identification of older studies through systematic reviews and hand search of bibliographies.ResultsFour studies met eligibility criteria. Drug treatment reduced the odds of a coronary heart disease event by 30% (summary odds ratio 0.70, 95% confidence interval 0.62 to 0.79) but not the odds of all cause mortality (0.94, 0.81 to 1.09). When statin drugs were considered alone, no substantial differences in results were found.ConclusionsTreatment with lipid lowering drugs lasting five to seven years reduces coronary heart disease events but not all cause mortality in people with no known cardiovascular disease.     

The association of viral activation with penicillin toxicity in guinea pigs and hamsters

Penicillin toxicity in the guinea pig may be manifested in several different ways, and it is proposed that these toxic effects be categorized into three syndromes: (1) toxic syndrome, characterized by acute fatal illness; (2) hemorrhagic syndrome, characterized by delayed illness with leukopenia and thrombocytopenia, and culminating in massive visceral hemorrhages; (3) chronic syndrome, characterized by retardation of growth and alopecia, a condition somewhat resembling “runt disease.” A virus having some of the properties of a parvovirus has been isolated repeatedly from animals ill or dying of penicillin-induced disease. This finding has been construed as being activation of a latent virus by this antibiotic, but the relationship, if any, of the phenomenon of viral activation to the syndromes produced by penicillin and its frequent lethal toxicity is unknown. That a strong association exists, however, has been established. Of some 60 guinea pigs which received injections of penicillin three developed tumors and four others were found to have gallstones. A virus similar or identical to the guinea pig virus also has been isolated from hamsters dying of penicillin-induced disease. It is hypothesized that the absorption of endotoxin, resulting from the well known change in intestinal flora caused by penicillin, produces a state of immunodeficiency which regularly gives rise to activation of a latent virus, and perhaps, rarely, to the development of malignant neoplasms.     

The changing hypothesis of the gut. The intestinal microbiome is increasingly seen as vital to human health

A rise in immune-related diseases has coincided with increasing levels of hygiene and antibiotic use. In our war against bacteria, are our gut microbiota collateral damage, and can we afford to lose their proven health effects?In many ways, humankind''s story of the past two centuries is that of a battle against dirt. From the development of the germ theory of disease to the modernization of sewerage systems in large cities, our growing awareness of the microorganisms and diseases that come with dirt has led to better public health and better hygiene. Yet, despite the increased lifespans and reduced infant mortality that have partly resulted from such improvements, the medical establishment has seen an increase in allergies and autoimmune diseases in the industrialized world in recent decades.… the medical establishment has […] seen an increase in allergies and autoimmune diseases in the industrialized world in recent decadesSeveral hypotheses have been put forward to explain the trend, ranging from exposure to environmental contaminants to changing diets. Yet none so far have given an entirely satisfactory answer. One of the most interesting suggestions that has enjoyed some popularity, but has never caught on with many researchers or clinicians, is the hygiene hypothesis, which suggests that humanity''s new-found cleanliness is itself the problem. The hypothesis, which was first proposed more than two decades ago [1], posits that childhood exposure to pathogenic organisms, especially certain bacteria, is essential for training the immune system to become tolerant of the many neutral or benevolent strains of microbiota that enter or reside in our bodies; without this exposure, the immune system overreacts to environmental cues. The problem with the hypothesis, though, is not that it is demonstrably wrong, but that it remains incomplete and has so-far lacked hard evidence of a link between exposure to pathogens and specific immunological mechanisms.In the post-genomic era, however, a new and more complete theory has emerged to explain the rise in allergic and autoimmune diseases. The ‘disappearing microbiota'' hypothesis does not point the finger at any single aspect of modern life, but suggests instead that some—if not all—developments over the past century, such as clean water, modern birth practices, pollution and the increasing use of antibiotics, have all contributed to a shift in the balance between different species and types of microorganism in the gut. This shift has, in turn, altered our symbiotic relationship with our gut microflora and the health benefits that our tiny passengers have conferred on us in the past.The disappearing microbiota theory has emerged with our growing knowledge of the importance of the microbiome in immunity and health [2]. One important implication is that changes in the composition of the microbiome, at the population level, must have consequences—potentially both positive and negative—and that these must be taken account of in health policy. “We and others have proposed the microbiota hypothesis,” said Sarkis Mazmanian, an Assistant Professor in the Division of Biology at the California Institute of Technology and a specialist in the evolutionary mechanisms of host–bacterial symbiosis. “It is not reduced infections that are mediating increases in allergic and autoimmune disease, as proposed by the hygiene hypothesis, but the lack of exposure to gut bacteria, as in the microbiota hypothesis” [3].According to Martin Blaser from the New York University School of Medicine, well known for his studies of the link between Helicobacter pylori and human diseases, this lack of exposure to gut bacteria is leading to a gradual shrinking of the human microbiome, at least in affluent nations. “This is the disappearing microbiota hypothesis,” Blaser said. “I came to this hypothesis through my work on Helicobacter, which is clearly disappearing. But the disappearance seems to have begun even before Helicobacter was discovered, and not because people are treating ulcers,” he explained, referring to the common practice of treating stomach ulcers with antibiotics designed to kill Helicobacter, following the discovery of its causal link with the condition [3].In fact, Blaser suggests that various factors are involved, including the overuse of antibiotics, as well as the chlorination of drinking water. “We know that chlorination of water impedes the spread of pathogens, but another thought is that it impedes the spread of commensals,” he explained. But Blaser does not think we should stop chlorinating water, nor does he want to turn back the clock on antibiotics. Even so, he does make an important point: “Antibiotics are wonder drugs, but everyone assumed they would be free, with no biological cost. When you start learning about our microbiome, it''s not too hard to imagine courses of antibiotics leading to extinctions, and when [the commensals] are gone, they''re gone. It was assumed that everything bounces back when the course is over, but there is more and more evidence that this is not the case.” Indeed, Blaser believes that the microbiome is gradually disappearing in terms of the total number of species present, but that this is hard to spot when there are so many and their numbers are so variable between individuals. “If you have thousands of species, you may not see it at first, but our hypothesis is that it is cumulative,” he explained.Regardless of whether the microbiome is shrinking in diversity, the idea that it is profoundly important in human health is gaining credibility, most immediately in inflammatory conditions directly relating to the gut, such as irritable bowel syndrome (IBS). Virtually nobody in the field disputes the idea that the microbiome is implicated in IBS, but it is less clear whether it is a cause, an effect, or a combination of both. The question is whether conditions such as IBS are caused by a priori changes in the microbiome, or whether such changes are symptoms of diagnostic value.The latest evidence that the micriobota have a protective effect in the gut comes from a recent study using mice [5]. Richard Flavell and colleagues at the Yale School of Medicine found that deficiencies in the NLRP6 inflammasome, engineered by a deletion mutation, resulted in an imbalance in the gut microbiota. The new micriobiota population was colitogeneic and led to inflammation of the colon. “But more importantly, we found that this pro-colitogenic flora was transmissible to wild-type mice that were co-housed with NLRP6 inflammasome-deficient mice, and induced exacerbated inflammatory bowel disease (IBD) in both NLRP6-deficient and co-housed wild-type mice,” Flavell explained.The ‘disappearing microbiota'' hypothesis […] suggests […] developments over the past century […] contributed to a shift in the […] species and types of microorganism in the gutIn other words, IBD can be transmitted to healthy animals that are not NLRP6 deficient, possibly through the spread of commensal bacteria or their products, such as metabolites, that might induce a change in the microflora. As Flavell indicated, although the NLRP6 inflammasome is known broadly to regulate the composition of the microbiota through release of the pro-inflammatory signalling cytokine interleukin-18 (IL-18), his latest work raises questions over the specifics of this process. “What types of microbial components or metabolites activate the NLRP6 inflammasome and how IL-18 regulates the ecology of the gut microbiota are important questions that remain to be resolved in the near future,” he said.This finding that metabolic conditions can be transferred to otherwise-healthy individuals should be followed up to see if it can be replicated in other animal models and ultimately in humans. This is of particular interest, given that the causes for the recent near-epidemic of obesity among some population groups have yet to be fully explained.Perhaps more probable, however, is that a change in the microbiome follows the onset of a condition such as obesity, rather than being the underlying cause. Even so, it might still be possible to reverse the syndrome by forcing a change in the composition of commensal bacteria in the gut. Work by Willem de Vos and colleagues at the Laboratory of Microbiology, Wageningen University, the Netherlands, is examining the potential for prebiotic and probiotic therapies that can be tested on humans, partly on existing published data from human and animal research [6].Another important indication emerging from the work of Flavell, de Vos and others is that the influence of the microbiome extends beyond metabolic disorders, for which few dispute the importance of commensal bacteria, to include disorders affecting a variety of organs and systems elsewhere in the body. In the case of some inflammatory liver diseases, this link was already known. There is a strong association, for example, between inflammatory gastrointestinal diseases—such as ulcerative colitis and the chronic liver disease primary sclerosing cholangitis, which involves scarring of the bile ducts of the liver [7]—and the presence of commensal bacteria. Flavell and colleagues found that dysbiosis associated with deficiency in the inflammasome regulates hepatic inflammatory processes in non-alcoholic fatty liver disease [8], which is highly prevalent in western societies. This study found that wild-type mice co-housed with inflammasome-deficient mice developed exacerbated steatohepatitis—a type of liver disease—as well as obesity, suggesting there is also a contagious element to some liver diseases.The liver is anatomically close to the intestines, but there is growing evidence that the influence of the microbiome permeates organs and systems elsewhere in the body, including the central nervous system. Studies have evaluated evidence for connections between the microbiome and multiple sclerosis, for example, suggesting that it could have potential both for diagnosis and therapies in future. Glenn Gibson, Professor of Food Microbial Sciences at the University of Reading in the UK, commented that such findings are “not too surprising because the metabolic output of gut bacteria is massive and bound to exert effects locally as well as systemically.” He explained that the effects “can be positive or negative for health, depending on which bugs and which metabolites are involved. But the really great news is that we are able to alter the situation to improve things and affect health. Unlike our genetics, the gut microbiome can be changed.” If, as Gibson suggests, the gut microbiome is responsible for about 70% of the total immune response, this could have profound consequences for the treatment of disease.However, for treatments based on probiotics or metabolites derived from bacteria to become widely available, there will have to be a marked shift in the attitude of some regulators, according to Gregor Reid, Chair in Human Microbiology and Probiotics at the Lawson Health Research Institute in London, Ontario, Canada. Reid and colleagues have conducted trials on the use of probiotic lactobacilli, a main component of the lactic acid bacteria group, to improve the treatment of vulvovaginal candidiasis (VVC) [9]. This is a condition caused by a strain of yeast that affects around 75% of sexually active women at some stage of their lives, causing vaginal itching and discharge. Reid was incensed when the European Food Safety Authority (EFSA) refused to approve this probiotic treatment for VVC in the European Union, leading to his publication of an opinion paper countering the EFSA critique [10]. “In this recent EFSA ruling, they stupidly disassociated nutrition from vaginal health, when in fact it is critical,” Reid explained.“When you start learning about our microbiome, it''s not too hard to imagine courses of antibiotics leading to extinctions…”At least this incident has highlighted issues relating to the use of, and approval for, treatments that attempt to alleviate conditions through manipulation of the microbiome. In particular, it highlights the need to nail down direct molecular associations between components of the human microbiome and specific cells or systems in the body that underpin conditions such as VVC. This is a main focus of research at the Functionality of the Intestinal Ecosystem (FinE) lab at the Micalis Institute in Paris, France. “The major priority of my own research team is to use functional metagenomics to identify signal molecules and crosstalk mechanisms linking human intestinal commensals and human cells using in vitro high throughput phenotyping systems,” explained Joël Doré, Vice Head of FinE. “The basic concept is that intestinal commensals constantly exchange signals with human cells, including intestinal epithelial cells, immune cells and even distally located peripheral tissues from adipose tissue to liver to brain.”It is probable that new diagnostic approaches will emerge from such metagenomic work on commensals even before treatments, which require a greater burden of proof and longer cycles of approval. It is not just regulators, but pharmaceutical companies that will have to embrace the idea of probiotics and metabolites before treatments become widely available in mainstream health care. There is great optimism from researchers in the field, but they still have to convince regulators and big pharma companies that the microbiome will become a main source of new therapies.     

Pandemics in the age of Twitter: content analysis of Tweets during the 2009 H1N1 outbreak

Background

Surveys are popular methods to measure public perceptions in emergencies but can be costly and time consuming. We suggest and evaluate a complementary “infoveillance” approach using Twitter during the 2009 H1N1 pandemic. Our study aimed to: 1) monitor the use of the terms “H1N1” versus “swine flu” over time; 2) conduct a content analysis of “tweets”; and 3) validate Twitter as a real-time content, sentiment, and public attention trend-tracking tool.

Methodology/Principal Findings

Between May 1 and December 31, 2009, we archived over 2 million Twitter posts containing keywords “swine flu,” “swineflu,” and/or “H1N1.” using Infovigil, an infoveillance system. Tweets using “H1N1” increased from 8.8% to 40.5% (R ² = .788; p<.001), indicating a gradual adoption of World Health Organization-recommended terminology. 5,395 tweets were randomly selected from 9 days, 4 weeks apart and coded using a tri-axial coding scheme. To track tweet content and to test the feasibility of automated coding, we created database queries for keywords and correlated these results with manual coding. Content analysis indicated resource-related posts were most commonly shared (52.6%). 4.5% of cases were identified as misinformation. News websites were the most popular sources (23.2%), while government and health agencies were linked only 1.5% of the time. 7/10 automated queries correlated with manual coding. Several Twitter activity peaks coincided with major news stories. Our results correlated well with H1N1 incidence data.

Conclusions

This study illustrates the potential of using social media to conduct “infodemiology” studies for public health. 2009 H1N1-related tweets were primarily used to disseminate information from credible sources, but were also a source of opinions and experiences. Tweets can be used for real-time content analysis and knowledge translation research, allowing health authorities to respond to public concerns.